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Also try CTRL+F "section" to look through batches of compilations focused on specific topics
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[SARS-CoV-2 pathway mapping]
https://www.kegg.jp/kegg-bin/show_pathway?hsa05171
https://www.genome.jp/kegg-bin/show_organism?org=hsa
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[Seasonality section]
SARS-2 is a seasonal climate-driven disease across both hemispheres
https://www.medrxiv.org/content/10.1101/2020.12.16.20248310v1
Day-night and seasonal variation of human gene expression across tissues
>Circadian and circannual cycles trigger physiological changes whose reflection on human transcriptomes remains largely uncharted
>We used the time and season of death of 932 individuals from GTEx to jointly investigate transcriptomic changes associated with those cycles across multiple tissues
>For most tissues, we found little overlap between genes changing expression during day-night and among seasons
>Although all tissues remodeled their transcriptomes, brain and gonadal tissues exhibited the highest seasonality, whereas those in the thoracic cavity showed stronger day-night regulation
>Core clock genes displayed marked day-night differences across multiple tissues, which were largely conserved in baboon and mouse, but adapted to their nocturnal or diurnal habits
>Seasonal variation of expression affected multiple pathways and were enriched among genes associated with SARS-CoV-2 infection. Furthermore, they unveiled cytoarchitectural changes in brain subregions. Altogether, our results provide the first combined atlas of how transcriptomes from human tissues adapt to major cycling environmental conditions
https://www.biorxiv.org/content/10.1101/2021.02.28.433266v1
Seasonal and Nonseasonal Longitudinal Variation of Immune Function
>1-y longitudinal analysis.
>Seasonality influences immune responses.
>Inflammatory markers, cell counts, and cytokine production show seasonality.
>Strong impact of age.
>on average, genetics accounted for almost 50% of the interindividual variance not already explained by age, sex, and body mass index
https://www.jimmunol.org/content/early/2021/07/14/jimmunol.2000133
[Seasonality section]
>COVID-19 patients had decreased GM metrics (GM density, volume, thickness, or area) with respect to controls in the following areas: left hippocampus (lower volume), left superior division of the lateral occipital cortex (lower GM density), transverse temporal gyrus (lower left volume), right middle temporal gyrus (lower thickness, lowest in the non-critical group), right superior temporal gyrus (lower thickness), right inferior parietal (lower thickness), right supramarginal gyrus (lower thickness, lowest in the non-critical group), right isthmus of the cingulate gyrus (lower area and volume, lowest in the non-critical group), right cuneus (lower thickness).
>Reductions observed in non-frontal areas were instead more prominent in non-critical patients and not correlated with inflammatory markers, suggesting a different pattern of the impact of COVID-19 on the GM.
https://www.medrxiv.org/content/10.1101/2021.05.19.21257316v1
>We show that SARS-CoV-2 may infect almost one third of the cells in the brain and the majority of these cells are astrocytes
>In astrocytes, SARS-CoV-2 infection results in marked changes in cellular metabolism.
>Since astrocyte metabolism is key to support neuronal function, we hypothesized that these changes could indirectly impact neurons.
>We also found that SARS-CoV-2 infection elicits a secretory phenotype in astrocytes that results in increased neuronal apoptosis.
>we evaluated individuals that did not have to be hospitalized (i.e. had mild respiratory symptoms), and nevertheless, we observed notable alterations of cortical thickness.
https://archive.is/ZyzSt
A model framework for projecting the prevalence and impact of Long-SARS-2 in the UK [long-term neurological damage and damage from asymptomatic infections is not counted within the model btw]
>The objective of this paper is to model lost Quality Adjusted Life Years (QALYs) from symptoms arising from COVID-19 in the UK population, including symptoms of 'long-COVID'. The scope includes QALYs lost to symptoms, but not deaths, due to acute COVID-19 and long COVID.
>The prevalence of symptomatic COVID-19, encompassing acute symptoms and long-COVID symptoms, was modelled using a decay function.
>Permanent injury as a result of COVID-19 infection, was modelled as a fixed prevalence.
>Both parts are combined to calculate QALY loss due to COVID-19 symptoms.
>Assuming a 60% final attack rate for SARS-CoV-2 infection in the population, we modelled 299,719 QALYs lost within 1 year of infection (90% due to symptomatic COVID-19 and 10% permanent injury) and 557,754 QALYs lost within 10 years of infection (49% due to symptomatic COVID-19 and 51% due to permanent injury).
>The UK Government willingness-to-pay to avoid these QALY losses would be £17.9 billion and £32.2 billion, respectively.
>Additionally, 90,143 people were subject to permanent injury from COVID-19 (0.14% of the population).
https://www.medrxiv.org/content/10.1101/2021.05.18.21252341v1
[]
Compare for England and Swine Flu pandemic of 2009
The Impact of Pandemic Influenza H1N1 on Health-Related Quality of Life: A Prospective Population-Based Study
>While the H1N1v influenza pandemic in 2009 was clinically mild, with a low case-fatality rate, the overall disease burden measured in quality-adjusted life years (QALY) lost has not been estimated. Such a measure would allow comparison with other diseases and assessment of the cost-effectiveness of pandemic control measures.
>Cases of H1N1v confirmed by polymerase chain reaction (PCR) and PCR negative cases with similar influenza-like illness (ILI controls) in 7 regions of England were sent two questionnaires, one within a week of symptom onset and one two weeks later, requesting information on duration of illness, work loss and antiviral use together with EQ-5D questionnaires. Results were compared with those for seasonal influenza from a systematic literature review. A total QALY loss for the 2009 pandemic in England was calculated based on the estimated total clinical cases and reported deaths.>A total of 655 questionnaires were sent and 296 (45%) returned. Symptoms and average illness duration were similar between confirmed cases and ILI controls (8.8 days and 8.7 days respectively). Days off work were greater for cases than ILI controls (7.3 and 4.9 days respectively, p=0.003). The quality-adjusted life days lost was 2.92 for confirmed cases and 2.74 for ILI controls, with a reduction in QALY loss after prompt use of antivirals in confirmed cases. The overall QALY loss in the pandemic was estimated at 28,126 QALYs (22,267 discounted) of which 40% was due to deaths (24% with discounting).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047534/
>In SARS-CoV-2-mediated ARDS, patients are hypovolemic due to a highly reduced level of aldosterone despite RAS activation. The cause of hypovolemia in SARS-2 patients is due to the lack of serotonin; this biomolecule plays important biological roles including stimulation of aldosterone secretion
>Fatigue and various degrees of mood disorders are other clinical manifestations of COVID-19 patients that are attributed to consequences of NAD, ATP, and serotonin reduction.
>serotonin reduction
https://www.mdpi.com/1422-0067/22/11/5438/pdf
>This novel insight of serotonin metabolism might be a key player underpinning GI symptoms and severity in patients with COVID-19 as altered serotonin signaling modulates the majority of pathological mechanisms in patients with FGIDs.
>PI-FGIDs have also been associated with dysregulation of gut motility, visceral hypersensitivity, microbial dysbiosis, intestinal barrier dysfunction, bile acid malabsorption, and alterations in serotonin metabolism[54,57]. Current data suggest that the resolution of the SARS-CoV-2 infection may lead to persistent GI dysfunction resembling certain aspects of PI-FGIDs
https://www.wjgnet.com/1007-9327/full/v27/i19/2341.htm
>We observed lower FA in the left anterior corona radiate of recovered COVID-19 patients showed significant positive correlations with the serotonin level.
https://archive.is/2I7FU
>SARS-Cov-2 spike protein fragment 674–685 protects mitochondria from releasing cytochrome c in response to apoptogenic influence
>SARS Cov-2 peptide 674–685 interacts with α7 nAChRs in cells and mitochondria.
https://www.sciencedirect.com/science/article/pii/S0006291X21007889
The women possibly at higher risk for Covid-19 that no one is talking about
https://edition.cnn.com/2021/05/23/health/women-covid-pcos-high-risk/index.html
https://archive.is/oR1VI
[]
Sex, Hormones, Immune Functions, and Susceptibility to Coronavirus Disease 2019 (SARS-2)–Related Morbidity
>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), uses two primary receptors, type II transmembrane serine protease and angiotensin-converting enzyme-2, for priming and cellular invasion, respectively. Both proteins have been demonstrated to be present in different concentrations in females and males, which may explain a mechanism for the reported higher case-fatality rate in males. Despite the known sex difference in COVID-19 disease mortality, preliminary data suggest there are certain female populations, including pregnant and menopausal women and possibly polycystic ovarian syndrome patients who are more susceptible to COVID-19–related morbidity. This commentary analyzes the interplay between sex differences, hormones, and the immune function in each of these populations with respect to the risk and severity of COVID-19 and proposes biological rationales to explain these differences.
>Preliminary data suggest that certain female populations, including pregnant and menopausal women and possibly women with polycystic ovarian syndrome, are more susceptible to coronavirus disease 2019 (COVID-19)–related morbidity.
https://journals.lww.com/greenjournal/Abstract/9900/Sex,_Hormones,_Immune_Functions,_and.112.aspx
Persistent clotting protein pathology in Long COVID/ Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin
>Many patients are also developing Long COVID/PASC after mild or asymptomatic infection, despite not being hospitalized.
>In the current study, we investigate if the lingering symptoms that individuals with Long COVID/PASC might be due to the presence of persistent circulating plasma clots that are resistant to fibrinolysis.
>Patients diagnosed with COVID-19 (before treatment) (N=15; 6 males and 5 females; mean age: 54.8 ± 15.3) and also patients with Type 2 Diabetes Mellitus (T2DM) (N=10; 7 males and 3 females; mean age: 59.2 ± 15.9) were included.
>In addition, patients that suffered from Long COVID/PASC (N=11; 3 males and 8 females; mean age: 55.7 ± 5.8), were included.
>There was a significant difference in PPP SAA1 concentrations between controls and acute COVID-19 (p = 0.02), and controls and Long COVID/PASC (p = 0.009).
>Here we show that PPP from Long COVID/PASC samples also have considerable anomalous (amyloid) clotlets, similar to that of acute COVID-19 PPP samples.
>Results presented in the current paper point to a significant failure in the fibrinolytic process during COVID-19 and also in patients with lingering Long COVID/PASC symptoms.
>Plasma proteins in both COVID-19 and Long COVID/PASC plasma samples are greatly resistant to breakdown in the presence of trypsin.
>Our results point to a nine-fold increase in α2AP in Long COVID/PASC vs controls and an eight-fold increase in Long COVID/PASC vs acute COVID19 for digested pellet deposits.
>There was a 17-fold increase in SAA4, between PPP in samples from Long COVID/PASC vs controls, and a six-fold increase when the comparison was between Long COVID/PASC over COVID-19.
>Of particular interest is the simultaneous presence of persistent anomalous (amyloid) clotlets and a pathological fibrinolytic system.
https://www.medrxiv.org/content/10.1101/2021.05.21.21257578v1
Long thread on the possibility of getting the coof from frozen foods, something that chinks absolutely love to blame their local transmissions on.
>The paper says that out of 400+ surface samples from the frozen fish, 50 had SARS2 genetic material and only 1 sample, after desperate efforts, was able to produce what looked like cytopathic effects (Fig 1). Not isolated virus. Just a picture of cells dying.
>The study sequenced the viruses and found they originated from a European lineage (the virus went from Wuhan to Europe and mutated into this lineage B1.1).
>Guess what. This lineage is basically all over the world right now.
https://twitter.com/Ayjchan/status/1354609310605705220
Newborn antibodies to SARS-CoV-2 detected in cord blood after maternal vaccination
>Maternal vaccination for Influenza and TDaP have been well studied in terms of safety and efficacy for protection of the newborn by placental passage of antibodies. Similar newborn protection would be expected after maternal vaccination against SARS-CoV-2 (the virus responsible for COVID-19). There is a significant and urgent need for research regarding safety and efficacy of vaccination against SARS-CoV-2 during pregnancy. Here, we report the first known case of an infant with SARS-CoV-2 IgG antibodies detectable in cord blood after maternal vaccination. Case presentation: A vigorous, healthy, full-term female was born to a COVID-19 naive mother who had received a single dose of mRNA vaccine for SARS-CoV-2 three weeks prior to delivery. Cord blood antibodies (IgG) were detected to the S-protein of SARS-CoV-2 at time of delivery
https://www.medrxiv.org/content/10.1101/2021.02.03.21250579v1
>we co-incubated authentic virus with a highly neutralizing plasma from a COVID-19 convalescent patient.
>The plasma fully neutralized the virus for 7 passages, but after 45 days, the deletion of F140 in the spike N-terminal domain (NTD) N3 loop led to partial breakthrough.
>At day 73, an E484K substitution in the receptor-binding domain (RBD) occurred, followed at day 80 by an insertion in the NTD N5 loop containing a new glycan sequon, which generated a variant completely resistant to plasma neutralization.
>Computational modeling predicts that the deletion and insertion in loops N3 and N5 prevent binding of neutralizing antibodies. The recent emergence in the United Kingdom and South Africa of natural variants with similar changes suggests that SARS-CoV-2 has the potential to escape an effective immune response and that vaccines and antibodies able to control emerging variants should be developed.
https://www.biorxiv.org/content/10.1101/2020.12.28.424451v1.full
A cautionary note on recall vaccination in ex-SARS-2 subjects
>There is no indication as to whether individuals who have recovered from COVID-19 should be vaccinated, and if so, if they should receive one or two vaccine doses.
>Here, we tested the antibody response developed after the first dose of the mRNA based vaccine encoding the SARS-CoV-2 full-length spike protein (BNT162b2) in 124 healthcare professionals of which 57 had a previous history of COVID-19 (ExCOVID).
>Post-vaccine antibodies in ExCOVID individuals increase exponentially within 7-15 days after the first dose compared to naive subjects (p<0.0001). We developed a multivariate Linear Regression (LR) model with l2 regularization to predict the IgG response for SARS-COV-2 vaccine.
>We found that the antibody response of ExCOVID patients depends on the IgG pre-vaccine titer and on the symptoms that they developed during the disorder, with anosmia/dysgeusia and gastrointestinal disorders being the most significantly positively correlated in the LR.
>Thus, one vaccine dose is sufficient to induce a good antibody response in ExCOVID subjects.
>This poses caution for ExCOVID subjects to receive a second jab both because they may have a overreaction of the inflammatory response and also in light of the current vaccine shortage.
https://www.medrxiv.org/content/10.1101/2021.02.01.21250923v2
Protein glycosylation is essential for SARS-CoV-2 infection
>SARS-CoV-2 extensively N-glycosylates its surface spike (S) proteins. This post-translational modification is essential to modulate protein conformation and host cell invasion. Each S monomer can be modified with up to 22 N-glycans.
>To meet the high demand of protein glycosylation during virus replication, SARS-CoV-2 upregulates the expression of host N-glycosylation genes. Although a substantial amount of detail is known about the structure of S protein N-glycans, the role of N-glycosylation in SARS-CoV-2 infection remains largely undetermined. Here, we investigated the essentiality of the host N-glycosylation pathway and viral N-glycans for SARS-CoV-2 infection. When either monkey or human cells were preincubated with glycosylation inhibitors, including FDA-approved iminosugars, virus infection was significantly reduced.
>This infection phenotype was confirmed after RNAi knockdown of several glycosylation genes. In addition, enzymatic deglycosylation of whole viral particles confirmed that accessible oligosaccharides on the SARS-CoV-2 surface are essential for host cell infection.
>Altogether, we show evidence that the normal functioning of the host N-glycosylation machinery is essential not only for SARS-CoV-2 to infect, but also to produce new functional virions. These findings open the door for developing new approaches targeting N-glycosylation against COVID-19.
https://www.biorxiv.org/content/10.1101/2021.02.05.429940v1
>In conclusion, this meta‐analysis of eight studies with more than 3700 patients shows a pooled proportion of 14.4% for newly diagnosed diabetes in hospitalized COVID‐19 patients.
https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14269
>COVID-19 as a Possible Cause of Myocarditis and Pericarditis
>At present, limited data have been published on cases with COVID-19 who develop pericarditis and pericardial effusion. Most reported cases have been associated myocardial involvement with troponin elevation.
https://www.acc.org/latest-in-cardiology/articles/2021/02/05/19/37/covid-19-as-a-possible-cause-of-myocarditis-and-pericarditis
>Diseasome and comorbidities complexities of SARS-CoV-2 infection with common malignant diseases
>This work also revealed ribosome biogenesis, wnt signaling pathway, ribosome, chemokine and cytokine pathways that are commonly deregulated in cancers and COVID-19.
https://academic.oup.com/bib/advance-article/doi/10.1093/bib/bbab003/6128841
>Incredible New Image Of SARS-Cov-2 Shows SARS-2 Virus Bound To A Kidney Cell
>Coronaviruses such as SARS-Cov-2 are only around 100 nanometers in diameter – or 100 billionths of a meter. That’s way below the limit for optical microscopes. Electron microscopes have been employed from the very first weeks of the pandemic to image the virus, but these instruments have certain drawbacks. To conduct electron microscopy, it is necessary to coat the cells in a thin layer of gold, which alters their properties.
>Helium ion microscopes don’t have these limitations. They can distinguish things over 400 times smaller than a coronavirus, and since they are not altering cells in any way, they can see how viruses and cells actually interact.
>“The study shows that the helium ion microscope is suitable for imaging coronaviruses – so precisely that the interaction between virus and host cell can be observed,” lead author Dr Natalie Frese, a physicist from Bielefeld University, said in a statement.
https://www.iflscience.com/health-and-medicine/incredible-new-image-of-sarscov2-shows-covid19-virus-bound-to-a-kidney-cell/
>Hiccups and psychosis: two atypical presentations of SARS-2
>Two previously healthy men in their 40s presented to the ER with very atypical manifestations of COVID-19. Neither of them complained of fever, cough, or shortness of breath. The first referred a 3-day history of hiccups that had not resolved with metoclopramide. The second presented with an acute episode of altered mental status. While the first case revealed lung involvement of the disease, the second case had a clean chest CT scan. These cases are relevant as manifestations of COVID-19 vary widely, especially in previously healthy young adults.
https://archive.is/PPB7p
>The adjusted seroprevalence of SARS-CoV-2 across Karnataka was 46.7%, suggesting approximately 31.5 million residents were infected, far greater than the 327076 cases reported by August 29, 2020.5 This discrepancy may be due to low testing rates (approximately 4000 per million population)5 and a large proportion of infections in Karnataka being asymptomatic.6
https://jamanetwork.com/journals/jama/fullarticle/2776292
>Hepatic vasculopathy and regenerative responses of the liver in fatal cases of COVID-19
>We show here secretion of virus into bile and that replication of SARS-CoV-2 occurs in liver tissues during COVID-19. Viral infection of HSPC was observed, comparable to that noted in lung alveolocyteprogenitors in the first variant of SARS-CoV-infections
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844358/
>During our pandemic period, there was a significantly decreased number of stroke codes but simultaneous increases in positivity rates, symptom severity, and inpatient codes. We postulate that this finding reflects the documented reluctance of patients to seek medical care during the pandemic, with the shift toward a greater proportion of inpatient stroke codes potentially reflecting the neurologic complications of the virus itself.
http://www.ajnr.org/content/early/2021/02/04/ajnr.A7038
>The Link Between ‘Alzheimer’s Gene’ and SARS-2
>A City of Hope-led research team found that the same gene that increases the risk for Alzheimer’s disease, ApoE4, can increase the susceptibility to and severity of COVID-19.
>The team’s next step is to continue studying the effects of the virus to better understand the role of ApoE4 in the neurological manifestations of COVID-19. Many people infected with COVID-19 have recovered, but long-term neurological effects such as severe headaches are still seen months after.
https://neurosciencenews.com/apoe4-covid-19-17676/
>SARS-CoV-2 membrane glycoprotein M antagonizes the MAVS-mediated innate antiviral response
https://pubmed.ncbi.nlm.nih.gov/33110251/
[]
https://www.drugtargetreview.com/news/72872/the-nf-κb-pathway-drives-fatal-inflammation-in-covid-19-say-scientists/
>The NF-κB pathway drives fatal inflammation in COVID-19, say scientists
[]
>Intracranial inflammatory mediators involved in SARS-CoV-2 neurological manifestations?
>They found an increase in intracranial inflammatory mediators such as IL-6, IL-8, IFNγ and MMP10, in the absence of viral neuroinvasion. IFNγ and its downstream effectors CXCL9, CXCL10 and CXCL11 were still elevated nearly 2 months after the infection and intracranial levels of MMP10 correlated with the degree of neurological dysfunction. These findings support the investigation of anti-inflammatory drugs to treat neurological symptoms following COVID-19.
https://archive.is/1iPLo
[]
>In this scenario, the release by immune effector cells of large amounts of pro-inflammatory cytokines (IFNα, IFNγ, IL-1β, IL-6, IL-12, IL-18, IL-33, TNFα, TGFβ) and chemokines (CXCL10, CXCL8, CXCL9, CCL2, CCL3, CCL5) precipitates and sustains the aberrant systemic inflammatory response
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211650/
Low level of Vitamin C and dysregulation of Vitamin C transporter might be involved in the severity of SARS-2 Infection
>A number of studies support the finding that a high dose of the vitamin helps boost the immune system
>It has been noted from previous studies that resting neutrophils contain high intracellular levels of vitamin C, around 1-2 mM, or about 10-100 fold higher than average plasma levels. This intracellular concentration only increases when neutrophils are activated and begin to undergo oxidative burst, with levels reaching 10-20 mM following stimulation
>Due to this phenomenon and vitamin C's antioxidant properties, it has been hypothesized that vitamin C plays a vital role in neutrophil function and thus essential for proper immune system response.
>adequate vitamin C levels are imperative for proper neutrophil function and normal immune system function. It is known that in patients with severe COVID-19 infection, hyperactivity within the immune system is rampant. However, there are indications that providing excessive vitamin C in those with deficient levels will allow for proper immune function, thus limiting and decreasing the severity of the infection
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801272
Impact of SARS-2 on Future Ischemic Stroke Incidence
>Ischemic stroke (IS) is now one of the well-documented additional clinical manifestation of COVID-19.
>Most COVID-19 related IS cases have been categorized as cryptogenic or embolic stroke of undetermined source (ESUS), which are most often suspected to have an undiagnosed cardioembolic source. COVID-19 is known to also cause cardiac dysfunction, heart failure, and atrial arrhythmias (AA), but the long-term impact of this cardiac dysfunction on stroke incidence is unknown.
>With millions afflicted with COVID-19 and the ever-rising infection rate, it is important to consider the potential long-term impact of COVID-19 on possible future IS incidence.
>Accomplishing these goals will require novel strategies that allow for diagnosis, data capture, and prediction of future IS risk using tools that are adaptable to the evolving clinical challenges such that patient care delivery and research
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849603
Proteinuria in SARS-2: prevalence, characterization and prognostic role
>This retrospective, observational, single center study included 153 patients, hospitalized with COVID-19 between March 28th and April 30th, 2020, in whom total proteinuria and urinary α1-microglobulin (a marker of tubular injury) were measured. Association with mortality was evaluated, with a follow-up until May 7th, 2020.
>According to the Kidney Disease Improving Global Outcomes staging, 14% (n=21) of the patients had category 1 proteinuria (<150 mg/g of urine creatinine), 42% (n=64) had category 2 (between 150 and 500 mg/g) and 44% (n=68) had category 3 proteinuria (over 500 mg/g). Urine α1-microglobulin concentration was higher than 15 mg/g in 89% of patients. After a median follow-up of 27 [14;30] days, the mortality rate reached 18%. Total proteinuria and urinary α1-microglobulin were associated with mortality in unadjusted and adjusted models. This association was stronger in subgroups of patients with normal renal function and without a urinary catheter
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823174
Seizure is a rare presenting manifestation of SARS-2
>Of 5872 people, who were admitted to hospitals in Iran with COVID-19 during the study period, 45 came to the emergency room with seizures. This makes seizure as the presenting manifestation of COVID-19 in 0.8 % of all patients with a severe illness. 93 % of the patients were 15 years of age and older. Four of the individuals presenting with seizures (9%) had a past history of epilepsy. Fifteen of these individuals (33 %) had other chronic medical conditions (e.g., cancer, diabetes mellitus, heart disease, etc.).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825948
Association of chronic anticoagulant and antiplatelet use on disease severity in SARS-CoV-2 infected patients
>Of 28,076, 720(3%) were on antiplatelets, 255(1%) were on anticoagulants, and 49(<1%) were on both
>The most common antiplatelet medications were aspirin (N=679) and clopidogrel (N=147)
>The most common anticoagulants were coumadin (N=130) and dabigatran (N=119)
>recent study in SARS-CoV-2 infected patients in a New York City health system showed no difference in survival, time to mechanical ventilation or hospital admission in those patients who were on anticoagulant or antiplatelet therapy at the time of SARS-CoV-2 diagnosis
>Our study in a diverse group of SARS-CoV-2 infected patients in Northern California also did not show an association between chronic anticoagulant and antiplatelet use with mortality, invasive ventilator use or inpatient hospitalizations.
>A recent study of European patients found lower survival and increased mortality risk in patients on chronic anticoagulation at the time of hospital admission for SARS-CoV-2 infection, though the prevalence of several comorbidities was high in that cohort
>conflicting results likely arise from differences in patient population with the New York and European patients being more severely ill with overall higher risk of hospitalization during the peak of illness in the spring of 2020
>Our population included a larger cohort of SARS-CoV-2 patients, the majority with mild disease and may be more representative of actual SARS-CoV-2 infection given expansion of testing over time
>there may still be certain subgroups of patients that may benefit from the use of anti-coagulation/platelet therapy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849957
The incidence, severity, and mortality of SARS-2 were common in non-blood group O. While blood group O was protected against SARS-2
>A total of (507) patients were included in this study. The study population was divided based on the ABO blood group into types A+, A−, B+, AB, O+, and O−. Blood group A was associated with high susceptibility of infection: group A, 381 (75.1%); and less common in group O, 97 (19.2%), group B, 18 (3.5%), and group AB, 11 (2.2%). The severity of COVID-19 infection was common in non-blood group O where (20 (7.1%), 4 (26.7%), 2 (11%), and 1 (9%) in type A+, A−, B+, and AB, respectively), while in type O 3.1%. And mechanically ventilated patients were 22 (5.9%), 2 (13.4%), 2 (11.1%), and 1 (1%). Mortality was high in blood groups A and B, 16 (4.37%) and 1 (5.5%), respectively, while in blood group O, it was 1%.
>There was no significant difference between the two groups regarding smoking index (mild, moderate, and heavy: 34.9/35%, 24.4/22.6%, 16.8/16.5%)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856613
Israel sees alarming leap in child coronavirus cases.
>In November 2020, some 400 toddlers had been diagnosed with COVID-19, by February that number had jumped to more than 5,800; health experts attribute massive increase to recently discovered mutations of pathogen
>Israel has seen a worrying rise in the number of coronavirus infections in teens, small children and even toddlers over the past few months, mainly due to the emergence of a number of variants of the pathogen in the country.
>Last November, some 400 toddlers under the age of two were diagnosed with COVID-19. By February, the number of infected toddlers had jumped to more than 5,800 - despite the third nationwide closure and Israel’s much-lauded mass vaccination campaign.
https://archive.is/psUaj
Physical exercise effects on the brain during SARS-2 pandemic: links between mental and cardiovascular health
>The infection caused by SARS-CoV-2 affects host cells binding to angiotensin-converting enzyme-2 (ACE2), which is the receptor for SARS-CoV-2
>If there is not enough oxygen supply the lungs and other tissues, such as the heart or brain, are affected. SARS-CoV-2 enhances ACE2 leading to inflammation and neuronal death with possible development of mood disorders, such as depression and anxiety
>Physical exercise also enhances the ACE2 expression. Conversely, the activation of ACE2/Ang 1-7/Mas axis by physical exercise induces an antiinflammatory and antifibrotic effect
>Physical exercise has beneficial effects on mental health enhancing IGF-1, PI3K, BDNF, ERK, and reducing GSK3β levels. In addition, physical exercise enhances the activity of PGC-1α/ FNDC5/Irisin pathway leading to neuronal survival and the maintenance of a good mental health
>Thus, SARS-CoV-2 infection leads to elevation of ACE2 levels through pathological mechanisms that lead to neurological and cardiovascular complications, while the physiological response of ACE2 to physical exercise improves cardiovascular and mental health.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829117
Selective Neuronal Mitochondrial Targeting in SARS-CoV-2 Infection Affects Cognitive Processes to Induce ‘Brain Fog’ and Results in Behavioral Changes that Favor Viral Survival
>studies have shown that SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) can directly or indirectly affect the central nervous system (CNS). Therefore, diseases associated with sequelae of COVID-19, or ‘long COVID’, also include serious long-term mental and cognitive changes, including the condition recently termed ‘brain fog’.
>Hypoxia in the microenvironment of select brain areas may benefit the reproductive capacity of the virus. It is possible that in areas of cerebral hypoxia, neuronal cell energy metabolism may become compromised after integration of the viral genome, resulting in mitochondrial dysfunction.
>Because of their need for constant high metabolism, cerebral tissues require an immediate and constant supply of oxygen.
>In hypoxic conditions, neurons with the highest oxygen demand become dysfunctional. The resulting cognitive impairment benefits viral spread, as infected individuals exhibit behaviors that reduce protection against infection.
>The effects of compromised mitochondrial function may also be an evolutionary advantage for SARS-CoV-2 in terms of host interaction.
>A high viral load in patients with COVID-19 that involves the CNS results in the compromise of neurons with high-level energy metabolism.
>Therefore, we propose that selective neuronal mitochondrial targeting in SARS-CoV-2 infection affects cognitive processes to induce ‘brain fog’ and results in behavioral changes that favor viral propagation.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845145
SARS-2 Specific skin changes related to SARS-CoV-2 Visualizing a Monumental Public Health Challenge
>Skin lesions linked with COVID-19 have been grouped into 6 categories with three distinct indicative patterns: vesicular (varicella-like), vasculopathic, and chilblains-like (including “COVID toes” and “COVID fingers”) plus three less suggestive ones: dermatitic, maculopapular, and urticarial morphologies. Vasculopathic changes are the most concerning, in some patients reflecting a devastating blood clotting dysfunction.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849605
Maternal and neonatal outcomes among women with and without SARS-CoV-2 infection during pregnancy - increased maternal morbidity with SARS-CoV-2 infection, but no differences in neonatal outcomes
>Of 2,714 women who delivered at the three hospitals, a diagnosis of SARS-CoV-2 was made in 122 (4.5%) women during the pregnancy. After coarsened exact matching, the study cohort included 486 women, 91 (18.7%) with a diagnosis of SARS-CoV-2 during pregnancy and 395 (81.3%) without this diagnosis. Demographic data showed that more Hispanic women were diagnosed with SARS-CoV-2 infection compared to other races. Compared to uninfected women, women with SARS-CoV-2 infection had statistically significant higher odds of the composite maternal outcome (6.6% vs. 14.3%; aOR 2.35 [95% CI 1.16-4.78). No statistically significant differences were seen between the groups regarding neonatal outcomes.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848503
Thromboelastography unchanged in pregnant women with SARS-2 compared to uninfected controls: a cohort study
>Twenty patients were included; 10 were SARS-CoV-2 positive and the remaining 10 were negative. There were no differences in baseline demographics between groups. None were admitted to ICU and all recovered well with favorable obstetric outcomes. There were no differences in TEG parameters (including R, Angle, MA) or in routine coagulation labs (platelet count, PT, PTT, and Fibrinogen) between those with or without COVID-19
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848505/
SARS-CoV-2 in pregnancy, placental fetal vascular malperfusion and the effect on fetal heart rate tracings
>Despite significant findings on placental pathology, no association was found between SV positivity and abnormal fetal heart tracings during labor. FHT was not a strong indicator of FVM in this cohort. Further studies are needed to fully understand the perinatal effects of the noted placental abnormalities in SV positive pregnant and laboring women
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848511
No association between ABO blood group and diagnosis or severity of SARS-2 in pregnant women. However, Rhesus positive women may be at a higher risk of SARS-2
>Of 586 pregnant women tested, 66 (11.3%) were positive. The most common ABO blood group in the cohort was O (52.2%) and 87.4% were Rh positive. Rates of the primary outcome, COVID-19 diagnosis, were not significantly different across ABO blood groups (P=0.47). There were also no significant differences in measures of COVID-19 severity among blood groups (Table). Compared to other blood groups, the risk of COVID-19 diagnosis was not significantly different in women with group O (13.1% vs 9.3%, adjusted OR 1.43; 95% CI 0.84, 2.4). Rh positive women were at a significantly higher risk of COVID-19 diagnosis (12.3% vs 4.1%, adjusted OR 3.38; 95% CI 1.03, 11.07) and a non-significant increased risk of symptoms (6.8% vs 2.7%, adjusted OR 2.67; 95% CI 0.63, 11.32), after adjusting for ABO blood group
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848569
611 Racial, ethnic and socioeconomic disparities in susceptibility to SARS-CoV-2 in pregnancy
>Of 2921 women with available SARS-CoV-2 antibody results, 446 (15.3%) were seropositive and 2475 (84.7%) were seronegative. The racial, ethnic and socioeconomic frequencies are presented in the tables. Non-Hispanic African-American and Hispanic women had a higher SARS-CoV-2 seroprevalence rate while Asian and non-Hispanic White women had a lower seroprevalence rate, p=0.00. Women in the low socioeconomic group were disproportionately affected by SARS-CoV-2 compared to women in the middle/high socioeconomic group, p=0.00.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848592
547 Neonatal outcomes of SARS-2 positive mothers
>2357 deliveries occurred out of which 1165 pregnant patients (44.4%) were universally tested. Ten out of 1165 (0.9%) mothers were tested positive for SARS-CoV-2 during preadmission universal screening. Eight (0.7%) were asymptomatic at the time of delivery, two developed (0.2%) mild disease at the time of admission. There was no (0/7) positive cases of SARS-CoV-2 from newborns delivered from positive mothers. No significant difference in neonatal morbidity noticed when compared to newborns of negative SARS-CoV-2 mothers during the same timeframe
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848579
Estimated SARS-CoV-2 Seroprevalence in Healthy Children and Those with Chronic Illnesses in The Washington Metropolitan Area as of October 2020
>The estimated SARS-CoV-2 seroprevalence in children was found to be 9.46% for the Washington Metropolitan area. Hispanic/Latinx individuals were found to have higher odds of seropositivity. While chronic medical conditions were not associated with having antibodies, previous fever and body aches were predictive symptoms
https://www.medrxiv.org/content/10.1101/2021.01.30.21250830v1
Differential Cytokine Signatures of SARS-CoV-2 and Influenza Infection Highlight Key Differences in Pathobiology
>Thirty-seven cytokines and chemokines were measured in plasma from 145 patients with COVID-19, 57 patients with influenza, and 30 healthy controls.
>Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was utilized to determine the cytokines most important in distinguishing severe COVID-19 and influenza. Mediation analysis was utilized to identify cytokines that mediate the effect of BMI on disease severity.
>IL-18, IL-1β, IL-6, and TNF-α were significantly increased in COVID-19 versus influenza patients while GM-CSF, IFN-γ, IFN-λ1, IL-10, IL-15, and MCP-2 were significantly elevated in the influenza group.
>In subgroup analysis based on disease severity, IL-18, IL-6, and TNF-α were elevated in severe COVID-19, but not severe influenza.
>Random forest analysis identified high IL-6 and low IFN-λ1 levels as the most distinct between severe COVID-19 and severe influenza.
>Finally, IL-1RA was identified as a potential mediator of the effects of BMI on COVID-19 severity.
https://www.medrxiv.org/content/10.1101/2021.01.29.21250317v1
Immuno-fibrotic drivers of impaired lung function in post-SARS-2 syndrome
>We performed a cohort study of subjects with lingering symptoms after COVID-19, collecting clinical data, pulmonary function tests, and plasma for multiplex biomarker profiling.
>Sixty-one subjects were enrolled across two academic medical centers at a median of 9 weeks post-COVID-19: n=13 (21%) mild/non-hospitalized, n=30 (49%) hospitalized/noncritical, and n=18 (30%) hospitalized/ICU.
>Dyspnea (69%) and cough (58%) were common. Pulmonary function at follow-up declined as acute COVID-19 severity increased (P<0.05), but did not correlate with symptoms.
>Partial least-squares discriminant analysis of biomarkers clustered subjects by COVID-19 severity. Lipocalin 2 (LCN2), matrix metalloproteinase-7 (MMP-7), and hepatocyte growth factor (HGF) were significantly higher in ICU subjects (P<0.05), and inversely correlated with pulmonary function (P<0.05).
>These host response profiles reflecting neutrophil activation, fibrosis signaling, and alveolar repair, respectively, may be novel therapeutic or prognostic targets in post-COVID-19 syndrome.
https://www.medrxiv.org/content/10.1101/2021.01.31.21250870v1
Schizophrenia is 2nd highest risk factor for dying of SARS-2, after age
https://www.livescience.com/schizophrenia-covid-19-death-risk-factor.html
Acute disseminated encephalomyelitis after severe acute respiratory syndrome coronavirus 2 vaccination: a case report
https://archive.is/5qEDF
A Community-Based Participatory Research to Assess the Feasibility of Ayurveda Intervention in Patients with Mild-to-Moderate SARS-2
>To assess the efficacy and safety of Ayurveda intervention in relieving symptoms of mild-to-moderate COVID-19, a community based participatory research framework was used.
>Prospectively 28 patients were enrolled with confirmed COVID-19 clinical stages of mild-to-moderate COVID-19, symptomatic, and between 20 to 70□years of age. Routine management was followed by all patients managing at home, additionally patents taking Ayurveda intervention for 14 consecutive days. The efficacy and safety of Ayurveda intervention were evaluated.
>There were suggestions of Ayurveda’s advantage in improved symptoms relief, clinical recovery in 7 days.
>However, a control group was not included but data triangulations from separate usual care found the difference statistically significant.
>Ayurveda intervention may potentially have a beneficial effect on patients with COVID□19, especially for those with mild to moderate symptoms. A further definitive large□scale clinical trial is necessary
https://www.medrxiv.org/content/10.1101/2021.01.20.21250198v1
Escape of SARS-CoV-2 (CCP+globohomo virus) 501Y.V2 ("South African") variants from neutralization by convalescent plasma
>We were the first to outgrow two variants of 501Y.V2 from South Africa, designated 501Y.V2.HV001 and 501Y.V2.HVdF002. We examined the neutralizing effect of convalescent plasma collected from six adults hospitalized with COVID-19 using a microneutralization assay with live (authentic) virus. Whole genome sequencing of the infecting virus of the plasma donors confirmed the absence of the spike mutations which characterize 501Y.V2. We infected with 501Y.V2.HV001 and 501Y.V2.HVdF002 and compared plasma neutralization to first wave virus which contained the D614G mutation but no RBD or NTD mutations. We observed that neutralization of the 501Y.V2 variants was strongly attenuated, with IC 6 to 200-fold higher relative to first wave virus. The degree of attenuation varied between participants and included a knockout of neutralization activity
https://www.medrxiv.org/content/10.1101/2021.01.26.21250224v1
[]
>200-fold reductions in the ability of antibodies to neutralize B.1.351
>included a knockout of neutralization activity
[?] Do examinations prepare students for higher education? A lesson from the SARS-2 lockdown
>Biological science courses require students to absorb a lot of new vocabulary and concepts, with examinations traditionally focusing on content recall rather than reasoning. Students who had entered university in September 2019 were compared with those arriving in September 2020 with respect to their knowledge of bioscience vocabulary and understanding of key concepts. Results showed no significant difference between those who had gone through the examination process in 2019 relative to those who had not, in 2020. This suggests the cramming of information for examinations has no detectable effect on the knowledge and understanding of biology that students take with them to university.
https://www.biorxiv.org/content/10.1101/2021.01.26.428208v1
>Engineering SARS-CoV-2 using a reverse genetic system
https://twitter.com/Ayjchan/status/1356247256467468293
An Evaluation of Traditional Persian Medicine for the Management of SARS-CoV-2
https://www.frontiersin.org/articles/10.3389/fphar.2020.571434
Supplementation with aged garlic extract improves both NK and γδ-T cell function and reduces the severity of cold and flu symptoms: A randomized, double-blind, placebo-controlled nutrition intervention
https://www.researchgate.net/publication/221780757_Supplementation_with_aged_garlic_extract_improves_both_NK_and_gd-T_cell_function_and_reduces_the_severity_of_cold_and_flu_symptoms_A_randomized_double-blind_placebo-controlled_nutrition_intervention
Persistent mild-to-moderate SARS-2 symptoms minimally impact the development of SARS-CoV-2 specific cellular immunity
>analyzis of SARS-CoV-2-specific cellular immunity in patients who experienced 8 days or fewer of COVID-19 symptoms, or symptoms persisting for 18 days or more.
>SARS-CoV-2 specific cellular immunity – defined as a subject having more than 50 IFN-γ producing SARSCoV-2 specific cells per 106 160 PBMC - was observed in 85.7% (13/14) of subjects classified as having a short duration of COVID-19 symptoms, while 94.7% (18/19) of subjects with a long duration of COVID-19 symptoms exhibited a positive response
>A statistically significant higher level of ORF3a and ORF7a reactivity was observed in individuals with longer periods of COVID-19 symptoms than in individuals with a short period of COVID-19 associated symptoms (Figure 2B), but most of these responses fell under the 50 SFC/10^6 PBMC threshold for positivity
>Furthermore, we observed that reactivity against the structural N protein from SARS-CoV-2 in convalescent COVID-19 patients correlates with the amount of reactivity against the seasonal human coronaviruses 229E and NL63.
>71.3% of individuals with a short period of COVID-19 symptoms and 68.4% of individuals that experienced a long period of COVID symptoms exhibiting a multivalent antigen response (Figure 2C). The most common multi-antigen reactivity pattern observed in individuals with a short duration of COVID-19 symptoms was a trivalent response against SARS179 CoV-2 Spike, N, and M proteins (Figure 3C). In contrast, the most common antigen reactivity pattern observed in individuals with a long duration of COVID-19 symptoms was a tetravalent response against SARS-CoV-2 Spike, N, M and ORF3a
>These results provide additional insight into the complex processes that regulate the development of cellular immunity against SARS-CoV-2 and related human coronaviruses
https://www.medrxiv.org/content/10.1101/2021.01.29.21250771v1
Emergence of first strains of Sars-CoV-2 lineage B.1.1.7 in Romania
>We have identified the first cases of the B.1.1.7 variant in samples collected from Romanian patients, of which one was traced to the UK region where the new variant was originally sequenced. Mutations in the Nsp3 protein, N844S and D455N and L15F in Orf3a were also detected, indicating common ancestry with UK strains as well as remote connections with strains from Nagasaki, Japan
https://www.medrxiv.org/content/10.1101/2021.01.29.21250643v1
Case: Persistent Cortical Blindness from SARS-2
https://archive.is/5CLgW
Oxford Kept SARS-2 Vaccine Trial Volunteers in Dark About Dosing Error, Letter Shows
https://archive.vn/wip/JB9HQ
Preliminary Evidence on Long SARS-2 in children
>129 children diagnosed with COVID-19 between March and November, 2020 were enrolled (mean age of 11 ± 4.4 years, 62 (48.1%) female). Subsequently, three developed Multisystem Inflammaory Syndrome (2.3%) and two myocarditis (1.6%).
>Patients were assessed on average 162.5 ± 113.7 days after COVID-19 microbiological diagnosis. 41.8% completely recovered, 35.7% had 1 or 2 symptoms and 22.5% had 3 or more. 52.7% had at least one symptom 120 days or more after diagnosis (Table 1). Table 2 provides details about persistence of symptoms according to severity and length of follow- up. Insomnia (18.6%), respiratory symptoms (including pain and chest tightness) (14.7%), nasal congestion (12.4%), fatigue (10.8%), muscle (10.1%) and joint pain (6.9%), and concentration difficulties (10.1), were the most frequently reported symptoms.
>Although they were more common in symptomatic or hospitalized children, they were also described in those individuals who were asymptomatic during acute phase. 29 out of the 68 (42.6%) children assessed ≥120 days from diagnosis were still distressed by these symptoms.
https://www.medrxiv.org/content/10.1101/2021.01.23.21250375v1.full.pdf
Impact of age, gender, ethnicity and prior disease status on immunogenicity following administration of a single dose of the BNT162b2 mRNA SARS-2 Vaccine: real-world evidence from Israeli healthcare workers, December-January 2020
https://www.medrxiv.org/content/10.1101/2021.01.27.21250567v1.full.pdf
SARS-CoV-2 RBD in vitro evolution follows contagious mutation spread, yet generates an able infection inhibitor
>Exploring the affinity limits for ACE2-RBD interaction
>[...] Selection of tighter binders can demonstrate the future path of SARS-CoV-2 evolution. In parallel, an ultra-tight binder can be used as an effective ACE2 blocker, inhibiting SARS-CoV-2 infection. We used the same approach and created library B5 (Fig. 1). B5 was selected against 200, 50 and 30 pM ACE2. Sorting with less than 100 pM bait was done after overnight incubation to reach equilibrium, in 50 ml solution to prevent the ligand depletion effect (as the number of ACE2 molecules becomes much lower than the number of RBD molecules). B5 resulted in the fixation of mutations E484K, Q498R, and N501Y in all sequences clones.
>N460K, S477N, and S494P were present with frequencies ˃ 20 %. Additional mutations identified were G446R, I468V, and F490Y.
>final selection aimed to achieve faster association-rates by pre-equilibrium selection
>This resulted in V445K, I468T, T470M and fixation of S477N in all sequences cloned. 5 minor mutations, N354E, K417T, V367W, S494P, and S514T, with only a single sequence each, were also identified. Among them also the K417T, which is present in the “Brazilian” variant 8.
>V445K and T470M require two nucleotide changes, demonstrating the efficiency of using multiple rounds of library creation on top of previous libraries (and not single clones)
>While SARSCoV-2 may evolve using other criteria (such as shown for the D614G mutation of the spike protein), we show that currently, the strongest evolutionary driver towards higher infectivity is the increase in RBD-ACE2 binding affinity.
>The rapid spread of N501Y in the population increases the likelihood for the emergence of the Q498R mutant, which will probably have even higher infectivity.
>This suggests that with the spread of the “British”, “Brazilian”, and “South African” variants, we project that the Q498R mutation will appear in the future, on top of these mutations.
>The synergism of Q498R with N501Y and E484K increases ACE2 binding by ~50- fold relative to WT.
https://www.biorxiv.org/content/10.1101/2021.01.06.425392v3.full.pdf
A Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO.IL-2Rγc KO. NOD) for SARS-2
>first Human Immune System (HIS)-humanized mouse model (DRAGA: HLA-A2.HLA-DR4.Rag1KO.IL-2RγcKO.NOD) for SARS-2 research. This mouse is reconstituted with human cord blood-derived, HLA-matched hematopoietic stem cells. It engrafts human epi/endothelial cells expressing the human ACE2 receptor for SARS-CoV-2 and TMPRSS2 serine protease co-localized on lung epithelia. HIS-DRAGA mice sustained SARS-CoV-2 infection, showing deteriorated clinical condition, replicating virus in the lungs, and human-like lung immunopathology including T-cell infiltrates, microthrombi and pulmonary sequelae. Among T-cell infiltrates, lung-resident (CD103+) CD8+ T cells were sequestered in epithelial (CD326+) lung niches and secreted granzyme B and perforin, indicating cytotoxic potential. Infected mice also developed antibodies against the SARS-CoV-2 viral proteins.
>HIS-DRAGA mice showed unique advantages as a surrogate in vivo human model
https://www.biorxiv.org/content/10.1101/2020.08.19.251249v3
An Autoantigen Atlas from Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of SARS-2
>COVID-19 is accompanied by a myriad of both transient and long-lasting autoimmune responses. Dermatan sulfate (DS), a glycosaminoglycan crucial for wound healing, has unique affinity for autoantigens (autoAgs) from apoptotic cells
>DS-autoAg complexes are capable of stimulating autoreactive B cells and autoantibody production. Using DS affinity, we identified an autoantigenome of 408 proteins from human fetal lung fibroblast HFL11 cells, at least 231 of which are known autoAgs
>Comparing with available COVID data, 352 proteins of the autoantigenome have thus far been found to be altered at protein or RNA levels in SARS-Cov-2 infection, 210 of which are known autoAgs. The COVID-altered proteins are significantly associated with RNA metabolism, translation, vesicles and vesicle transport, cell death, supramolecular fibrils, cytoskeleton, extracellular matrix, and interleukin signaling
>They offer clues to neurological problems, fibrosis, smooth muscle dysfunction, and thrombosis. In particular, 150 altered proteins are related to the nervous system, including axon, myelin sheath, neuron projection, neuronal cell body, and olfactory bulb. An association with the melanosome is also identified. The findings from our study illustrate a strong connection between viral infection and autoimmunity.
>The vast number of COVID-altered proteins with propensity to become autoAgs offers an explanation for the diverse autoimmune complications in COVID patients. The variety of autoAgs related to mRNA metabolism, translation, and vesicles raises concerns about potential adverse effects of mRNA vaccines. The COVID autoantigen atlas we are establishing provides a detailed molecular map for further investigation of autoimmune sequelae of the pandemic
https://www.biorxiv.org/content/10.1101/2021.01.24.427965v1
Human embryonic stem cell-derived cardiomyocytes express SARS-CoV-2 host entry proteins: screen to identify inhibitors of infection
>An ACE2 antibody, that has been shown previously to neutralize pseudotyped virus and SARS-CoV-2 infection, was effective in our drug screen, significantly reducing infection level to 2.9 ± 0.4 %, as was DX600, the ACE2 peptide antagonist. DX600 forms multiple interactions with the catalytic site, that is distinct from the receptor binding domain of the virus, but may be sufficient to change the conformation of ACE2, or induce steric hindrance, to inhibit spike binding
>Camostat and E64d, inhibitors of the accessory proteins TMPRSS2 and cathepsins respectively, significantly reduced infection levels to 20.5 ± 6.5 % and 7.8 ± 1.7 %. A mix of camostat and E64d effectively reduced infection rate as well (6.5 ± 1.5 %) but this was not significantly different to E64d treatment alone. These results suggest that inhibition of viral entry can be achieved at distinct steps of viral entry and processing. Importantly, camostat is already clinically approved in Japan where it is used to treat chronic pancreatitis, and is considered well tolerated and safe19,20 . Additionally, camostat has been previously confirmed as an effective inhibitor of infection
.
>benztropine, a small molecule inhibitor of the potential ancillary protein for viral entry, B0AT1, also successfully reduced pseudotyped virus infection levels (28.9 ± 8.8 %). The compound is used clinically as an adjunct in the therapy of all forms of parkinsonism but the precise mechanisms behind its inhibition of viral infection require further investigation
https://www.biorxiv.org/content/10.1101/2021.01.22.427737v1.full.pdf
Case report: SARS-CoV-2 in carotid body
>The carotid body plays a role in peripheral arterial chemoreception, in metabolic and immune sensing, and could also be a route of nervous system invasion by SARS-CoV-2. Involvement of the carotid body by SARS-CoV-2 may explain silent hypoxemia and thus could also contribute to increased morbidity and mortality in COVID-19 patients
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820831
SARS-CoV-2 neutralizing antibodies in patients with varying severity of acute SARS-2 illness
>early appearance of SARS-CoV-2 NAbs at high levels was not associated with milder disease nor with early clearance of the virus. Early appearance of NAbs has previously shown to occur in those with severe disease compared to those with mild illness17. It was recently shown that a high frequency of extrafollicular B cells development is seen in COVID-19, which correlated with disease severity. These extrafollicular B cells were responsible for development of development of SARS-CoV-2 specific neutralizing antibodies, very early during illness, which was shown to associate with severe disease18. In addition to production of NAbs by extrafollicular B cells, the early appearance of NAbs in patients with more severe disease could be due to the boosting of NAbs specific to previous coronaviruses. Therefore, early appearance of such cross-reactive antibody responses could have a potential to cause severe illness by antibody dependent enhancement (ADE)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819970
Variability in codon usage in Coronaviruses is mainly driven by mutational bias and selective constraints on CpG dinucleotide
>We present a comprehensive analysis of the composition and codon usage bias of the 82 Orthocoronavirinae members, infecting 47 different avian and mammalian hosts
>Our results clearly establish that synonymous codon usage varies widely among viruses and is only weakly dependent on the type of host they infect. Instead, we identify mutational bias towards AT-enrichment and selection against CpG dinucleotides as the main factors responsible of the codon usage bias variation
>Further insight on the mutational equilibrium within Orthocoronavirinae revealed that most coronavirus genomes are close to their neutral equilibrium, the exception is the three recently-infecting human coronaviruses, which lie further away from the mutational equilibrium than their endemic human coronavirus counterparts
>Finally, our results suggest that while replicating in humans SARS-CoV-2 is slowly becoming AT-richer, likely until attaining a new mutational equilibrium
https://www.biorxiv.org/content/10.1101/2021.01.26.428296v1
Growing evidence points to a range of musical medical benefits for ailments from stroke to Parkinson’s
>Khan’s 2020 delirium work is another example of a growing number of clinical trials, which are still typically small. Each of the 52 patients in this case had undergone mechanical ventilation in the ICU for about a day and then were assigned to a control (no music) or one of three treatment groups: listening to personalized playlists based on their music taste, generalized relaxing music chosen by a music therapist, or an audiobook such as Harry Potter and the Chamber of Secrets. Regardless of their treatment group, every patient listened for two hour-long sessions a day for one week. The researchers assessed patients daily to evaluate delirium, anxiety, and pain, for up to seven days. Eighty percent of the patients said that they enjoyed listening to the music. And among the treatment groups, general relaxing music resulted in the most delirium-free days (three, on average) and lowest delirium severity on a standardized seven-item scale.
> the largest-ever music intervention trial is now ongoing. Called Music Interventions for Dementia and Depression in Elderly Care (MIDDEL), it involves an estimated 1,000 patients across multiple European countries and Australia. The trial compares the effects of several music interventions on dementia and depression in residents of elder care facilities, age 65 or older
https://www.pnas.org/content/118/4/e2025750118
Estimation of the SARS-CoV-2 infection fatality rate in Germany
>The base case uses data on RKI nowcasted cases and backward-shifted fatalities from March 2 until May 1, 2020. A robustness check varies the end date from April 1 to June 1.
>Due to asymptomatic or mild courses of COVID-19, many infections remain undetected. Reported case fatality rates - COVID-19-associated deaths divided by number of detected infections - are therefore poor estimates of the IFR. Endogenous changes of the population at risk of a SARS-CoV-2 infection, changing test practices and an improved understanding of the pathogenesis of COVID-19 further exacerbate the estimation of the IFR. Here, we propose a strategy to estimate the IFR of SARS-CoV-2 in Germany that combines official data on reported cases and fatalities supplied by the Robert Koch Institute (RKI) with data from seroepidemiological studies in two infection hotspots, the Austrian town Ischgl and the German municipality Gangelt, respectively. For this purpose, we use the law of total probability to derive an approximate formula for the IFR that is based on a set of assumptions regarding data quality and test specificity and sensitivity. The resulting estimate of the IFR in Germany of 0.83\% (95\% CI: [0.69\%; 0.98\%])
https://www.medrxiv.org/content/10.1101/2021.01.26.21250507v1
[?] Contamination of air and surfaces in workplaces with SARS-CoV-2 virus: a systematic review
>Low level contamination of air and surfaces in hospitals with SARS-CoV-2 RNA have been reported during the Covid-19 pandemic.
>Limited data have published from non-healthcare settings.
>Typically, around 6% of air and surface samples in hospitals were positive for SARS-COV-2 RNA, although there is very limited data for non-healthcare settings.
>The quality of the available measurement studies is generally poor, with little consistency in the sampling and analytical methods used.
>Few studies report the concentration of SARS-CoV-2 in air or as surface loading of virus RNA, and very few studies have reported culture of the virus.
>The best estimate of typical air concentrations in health care settings is around 0.01 SARS-CoV-2 virus RNA copies/m3
https://www.medrxiv.org/content/10.1101/2021.01.25.21250233v1
An effect of the SARS-2 pandemic: significantly more complicated appendicitis due to delayed presentation of patients!
>A total of 306 patients were included in this evaluation. Sixty-five patients presented during the 2020 COVID-19 pandemic lockdown (group A), and 241 patients in previous years (group B: 2017–2019). The number of consultations for acute appendicitis decreased by almost 20 percent during the pandemic compared with previous periods, with a significant increase in complicated appendicitis (52% in group A versus 20% in group B, p < 0,001.). Comparing the two groups, significant differences were also noted in the duration of symptoms (symptoms > 48h in 61% and 26%, p < 0,001), the intervention time (77 vs 61 minutes, p = 0,002), length of hospital stay (hospitalization of > 2 days in 63% and 32%, p < 0.001) and duration of antibiotic treatment (antibiotics > 3 days in 36% and 24% p = 0.001).
>The COVID-19 pandemic resulted in a decreased number of consultations for acute appendicitis, with a higher proportion of complicated appendicitis, most likely due to patient delay in consulting the emergency department at symptom onset. Patients and general practitioners should be aware of this problem to avoid a time delay from initial symptoms to consultation.
https://www.medrxiv.org/content/10.1101/2021.01.23.21250358v1
[]
Acute appendicitis may be associated with SARS-2 (with case reports)
https://archive.vn/UGIg4
SARS-CoV-2 infection in pregnancy is associated with robust inflammatory response at the maternal-fetal interface
>In this study of pregnant women with and without COVID-19, we assessed viral and immune dynamics at the placenta during maternal SARS-CoV-2 infection.
>Amongst uninfected women, ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term.
>Term placentas from women infected with SARS-CoV-2, however, displayed a significant increase in ACE2 levels.
>Using immortalized cell lines and primary isolated placental cells, we determined the vulnerability of various placental cell types to direct infection by SARS-CoV-2 in vitro.
>Yet, despite the susceptibility of placental cells to SARS-CoV-2 infection, viral RNA was detected in the placentas of only a subset (∼13%) of women in this cohort.
>Through single cell transcriptomic analyses, we found that the maternal-fetal interface of SARS-CoV-2-infected women exhibited markers associated with pregnancy complications, such as preeclampsia, and robust immune responses, including increased activation of placental NK and T cells and increased expression of interferon-related genes.
>Overall, this study suggests that SARS-CoV-2 is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion.
>While this likely represents a protective mechanism shielding the placenta from infection, inflammatory changes in the placenta may also contribute to poor pregnancy outcomes and thus warrant further investigation
https://www.medrxiv.org/content/10.1101/2021.01.25.21250452v1
Molecular Dynamics Reveals the Effects of Temperature on Critical SARS-CoV-2 Proteins
>we employ Molecular Dynamics (MD) simulations to explore the effect of temperature on four critical SARS-CoV-2 proteins. Our work demonstrates that the spike Receptor Binding Domain (RBD), Main protease (Mpro), and nonstructural protein 3 (macro X) possesses extreme thermos-stability when subjected to temperature variations rendering them attractive drug targets. Furthermore, our findings suggest that these four proteins are well adapted to habitable temperatures on earth and are largely insensitive to cold and warm climates. Furthermore, we report that the critical residues in SARS-CoV-2 RBD were less responsive to temperature variations as compared to the critical residues in SARS-CoV. As such, extreme summer and winter climates, and the transition between the two seasons, are expected to have a negligible effect on the stability of SARS-CoV-2 which will marginally suppress transmission rates until effective therapeutics are available world-wide
https://www.biorxiv.org/content/10.1101/2021.01.24.427990v2
The CXCR6/CXCL16 axis links inflamm-aging to disease severity in SARS-2 patients
>Advancing age and chronic health conditions, significant risk factors for severe COVID-19, are associated with a pro-inflammatory state, termed inflamm-aging.
>CXCR6+ T cells are known to traffic to the lung and have been reported to increase with age.
>The ligand of CXCR6, CXCL16, is constitutively expressed in the lung and upregulated during inflammatory responses and the CXCR6/CXCL16 axis is associated with severe lung disease and pneumonia.
>[!] Genome-wide association studies have also recently identified 3p21.31, encompassing the CXCR6 gene, as a susceptibility locus for severe COVID-19.
>We assessed numbers T cells expressing the chemokine receptor CXCR6 and plasma levels of CXCL16, in control and COVID-19 patients.
>Results demonstrated that circulating CD8+CXCR6+ T cells were significantly elevated with advancing age, yet virtually absent in patients with severe COVID-19.
>Peripheral levels of CXCL16 were significantly upregulated in severe COVID-19 patients compared to either mild COVID-19 patients or SARS-CoV-2 negative controls. This study supports a significant role of the CXCR6/CXCL16 axis in the immunopathogenesis of severe COVID-19
https://www.biorxiv.org/content/10.1101/2021.01.25.428125v1
UUbiquitin ligase RIPLET mediates polyubiquitination of RIG-I and LGP2 and regulates the innate immune responses to SARS-CoV-2 infection
>RIG-I, a cytoplasmic viral RNA sensor, is crucial for innate antiviral immune responses; however, there are controversies about RIG-I regulatory mechanism by several ubiquitin ligases and LGP2. Our genetic study revealed that the RIPLET ubiquitin ligase was a general activating factor for RIG-I signaling, whereas another ubiquitin ligase, TRIM25, activated RIG-I in a cell-type-specific manner. These RIPLET and TRIM25 functions were modulated by accessory factors, such as ZCCH3C and NLRP12. Interestingly, we found an additional role of RIPLET in innate immune responses. RIPLET induced delayed polyubiquitination of LGP, resulting in the attenuation of excessive cytokine expression at the late phase. Moreover, RIPLET was involved in the innate immune responses against SARS-CoV-2
>RIPLET fine-tunes innate immune responses via polyubiquitination of RIG-I and LGP2 against virus infection, including SARS-CoV-2
https://www.biorxiv.org/content/10.1101/2021.01.25.428042v1
Biomarkers of endothelial dysfunction and outcomes in SARS-2 patients: a systematic review and meta-analysis
>A literature search was conducted on online databases for observational studies evaluating biomarkers of endothelial dysfunction and composite poor outcomes in COVID-19 patients.
>A total of 1187 patients from 17 studies were included in this analysis. The estimated pooled means for von Willebrand Factor (VWF) antigen levels in COVID-19 patients was higher compared to healthy control (306.42 [95% confidence interval (CI) 291.37-321.48], p<0.001; I2:86%), with the highest VWF antigen levels was found in deceased COVID-19 patients (448.57 [95% CI 407.20-489.93], p<0.001; I2:0%). Meta-analysis showed that higher plasma levels of VWF antigen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 antigen (PAI-1) antigen, and soluble thrombomodulin (sTM) were associated with composite poor outcome in COVID-19 patients ([standardized mean difference (SMD) 0.74 [0.33-1.16], p<0.001; I2:80.4%], [SMD 0.55 [0.19-0.92], p=0.003; I2:6.4%], [SMD 0.33 [0.04-0.62], p=0.025; I2:7.9%], and [SMD 0.55 [0.10-0.99], p=0.015; I2:23.6%], respectively). Conclusion. The estimated pooled means shows increased levels of VWF antigen in COVID-19 patients. Several biomarkers of endothelial dysfunction, including VFW antigen, t-PA, PAI-1, and sTM, are significantly associated with increased composite poor outcome in patients with COVID-19
https://www.medrxiv.org/content/10.1101/2021.01.24.21250389v1
Lysosomal-Immune Axis Is Associated with SARS-2 Disease Severity: Insights from Patient Single Cell Data
>In this study, we analyzed publicly available single-cell RNA-seq data from 75076 cells sequenced from clinically staged COVID-19 patients using a network approach and identified lysosomal-immune axis as a factor significantly associated with disease severity. Our results suggest modulation of lysosomal-immune pathways may present a novel drug-targeting strategy to attenuate SARS-Cov-2 infections.
https://www.biorxiv.org/content/10.1101/2021.01.27.428394v1
Novel SARS-2 phenotype definitions reveal phenotypically distinct patterns of genetic association and protective effects
https://www.medrxiv.org/content/10.1101/2021.01.24.21250324v1
Distinct Autoimmune Antibody Signatures Between Hospitalized Acute SARS-2 Patients, SARS-CoV-2 Convalescent Individuals, and Unexposed Pre-Pandemic Controls
>an assessment of autoimmune antibodies in convalescent SARS-CoV-2 patients has not yet been reported
>We compared the levels of 18 different IgG autoantibodies (AABs) between four groups
>(1) unexposed pre-pandemic subjects from the general population (n = 29)
>(2) individuals hospitalized with acute moderate to severe COVID-19 (n = 20)
>(3) convalescent SARS-COV-2-infected subjects with asymptomatic to mild viral symptoms during the acute phase with samples obtained between 1.8 and 7.3 months after infection (n = 9)
>(4) unexposed pre-pandemic subjects with systemic lupus erythematous (SLE) (n = 6)
>Total IgG and IgA levels were also measured from subjects in groups 1-3 to assess non-specific pan-B cell activation.
>As expected, in multivariate analysis, AABs were detected at much higher odds in SLE subjects (5 of 6, 83%) compared to non-SLE pre-pandemic controls (11 of 29, 38%).
>AAB detection (% of subjects with one or more autoantibodies) was higher in SARS-CoV-2 infected convalescent subjects (7 of 9, 78%) and subjects with acute COVID-19 (12 of 20, 60%) compared with non-SLE pre-pandemic controls, but was not statistically significant among the latter
>Within the convalescent subject group, AABs were detected in 5/5 with reported persistent symptoms and 2/4 without continued symptoms.
>The AABs defining SARS-COV-2 infected from pre-pandemic subjects are widely associated with myopathies, vasculitis, and antiphospholipid syndromes, conditions with some similarities to COVID-19.
>Compared to pre-pandemic non-SLE controls, subjects with acute COVID-19 had higher total IgG concentration but convalescent subjects did not; no differences in total IgA levels were found between groups
https://www.medrxiv.org/content/10.1101/2021.01.21.21249176v1
[!] Rather, one of 30 monkeys had lung pathology and bronchoalveolar lavage (BAL) cytokine levels suggestive of enhanced lung disease
The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates
>A safety concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated potent NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike protein from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV-1 infection
>Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of antibody binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement
>However, both in vitro neutralizing and infection-enhancing RBD or infection-enhancing NTD antibodies protected from SARS-CoV-2 challenge in non-human primates and mice.
>using monkey and mouse models of SARS-CoV-2 infection, none of these infection-enhancing antibodies consistently augmented SARS-CoV-2 lung viral load, infectious virus in the lung, or lung disease pathology in vivo. Rather, one of 30 monkeys had lung pathology and bronchoalveolar lavage (BAL) cytokine levels suggestive of enhanced lung disease
https://www.biorxiv.org/content/10.1101/2020.12.31.424729v1
https://www.biorxiv.org/content/10.1101/2020.12.31.424729v1.full.pdf
[]
>ADE in respiratory infections is included in a broader category named enhanced respiratory disease (ERD), which also includes non-antibody-based mechanisms such as cytokine cascades and cell-mediated immunopathology
https://archive.vn/vvfrv
NIH study uncovers blood vessel damage and inflammation in SARS-2 patients’ brains but no infection
https://archive.vn/3wJAx
SARS-CoV-2 escape in vitro from a highly neutralizing SARS-2 convalescent plasma
https://www.biorxiv.org/content/10.1101/2020.12.28.424451v1
De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2
https://science.sciencemag.org/content/370/6521/1208
New paper showing IFITMs inhibit SARS-CoV-2 endosomal entry, but IFITM3 conversely ENHANCES virus fusion at the plasma membrane. Distinct mechanisms at play. High TMPRSS2 shifts balance --> enhancement.
https://www.embopress.org/doi/abs/10.15252/embj.2020106501
https://www.biorxiv.org/content/10.1101/2020.08.11.246678v1.full
There could be a competition between Furin cleavage and heparan Sulfate binding
https://www.biorxiv.org/content/10.1101/2020.08.10.241414v1
IFITMs facilitate SARS-CoV-2 infection
https://www.biorxiv.org/content/10.1101/2020.08.18.255935v1
Lung cell infections
https://www.biorxiv.org/content/10.1101/2020.08.18.255935v1
Neutralizing antibody against SARS-CoV-2 spike in SARS-2 patients, health care workers and convalescent plasma donors
https://insight.jci.org/articles/view/143213/
Modeling Multi-organ Infection by SARS-CoV-2 Using Stem Cell Technology
https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30550-6
https://justpaste.it/img/4d35e54e8409e3dc30b7a195d68acdad.jpg
Reviewing findings from past studies that suggest CNS involvement of SARS-CoV-2
>Involvement of the nervous system in COVID-19: The bell should toll in the brain
https://www.sciencedirect.com/science/article/pii/S0024320520313217
https://justpaste.it/img/f6ee44430e77780fe4bfbd5ef9a0bf42.jpg
Researchers determine how the SARS-CoV-2 virus hijacks and rapidly causes damage to human lung cells
https://archive.vn/L7ebo
Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2
>SARS-CoV-2 infection in induced lung cells is characterized by phosphoproteomics
>Analysis of response reveals host cell signaling and protein expression profile
>Comparison to studies in undifferentiated cell lines shows unique pathology in iAT2s
>Systems-level predictions find druggable pathways that can impede viral life cycle
https://archive.vn/jlUJX
‘Matrix microscopy’: Powerful stargazing tech allows scientists to see directly through skulls without need for surgery
>Direct observation of live brains is difficult and requires invasive and dangerous surgery to cut through skin and bone. Now scientists can peer through skulls thanks to powerful technology borrowed from the field of astronomy.
>Porous and often inconsistent structures like bone tend to scatter light in unpredictable ways, frustrating efforts to ‘see’ through them using medical technology.
>However, scientists have now discovered a new method to create a clear image of what lies behind the skull from scattered infrared light shone by a laser.
>“Our microscope allows us to investigate fine internal structures deep within living tissues that cannot be resolved by any other means,” said physicists Seokchan Yoon and Hojun Lee from Korea University.
>The new imaging technology, known as laser-scanning reflection-matrix microscopy (LS-RMM), is so called because it derives a complete dataset of input-output response from the scattered laser light.
>In other words, some of the laser's photons can pass through the skull while others are scattered in a variety of different directions. The new process takes data derived from all of the photons into account to build a more complete picture of the brain behind the bone wall, by correcting any distortions.
>“This will greatly aid us in early disease diagnosis and expedite neuroscience research,” the researchers say.
>For now, one major drawback of the method is the sheer volume of computational power required to make sense of the reflection matrix. But the technique is still in its infancy and advances in computational power continue on a regular basis.
https://archive.vn/34WFO
Steam inhalation therapy found to inactivate SARS-CoV-2 virions
https://www.news-medical.net/news/20201130/Steam-inhalation-therapy-found-to-inactivate-SARS-CoV-2-virions.aspx
Emetine as an antiviral agent suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E: An in vitro study
>emetine targets SARS-CoV-2 protein synthesis which is mediated via inhibiting the interaction of SARS-CoV-2 RNA with eIF4E. This is a novel mechanistic insight on the antiviral efficacy of emetine. In vitro antiviral efficacy against SARS-CoV-2 and its ability to protect chicken embryos against IBV suggests that emetine could be repurposed to treat COVID-19
https://www.biorxiv.org/content/10.1101/2020.11.29.401984v1
The invasion of the CNS by SARS-CoV-2, as shown recently in areas like the brainstem that control the normal breathing process with nuclei like the pre-Bötzinger complex (pre-BÖTC), may explain why some of the patients with SARS-2, who have been reported to have recovered from pneumonia, could not be weaned from invasive mechanical ventilation and the occurrences of acute respiratory arrests seen in COVID-19
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422910/
Heart Failure Seen in Baby With SARS-2
https://archive.is/f512F
A case of limbic encephalitis associated with asymptomatic SARS-2 infection
https://jnnp.bmj.com/content/91/11/1229
SARS-CoV-2 highly conserved s2m element dimerizes via a kissing complex and interacts with host miRNA-1307-3p
>In this study, we identified a 4-nt palindrome (GUAC) within the terminal loop of the SARS-CoV-2 s2m element, which we show is involved in homodimeric RNA-RNA kissing complex formation. Furthermore, we show that this kissing dimer is able to undergo subsequent conversion into a thermodynamically stable duplex conformation, facilitated by the chaperone activity of the SARS-CoV-2 N protein, a process that may stabilize a dimerized formof the gRNA.
>this mechanism has been described previously in both hepatitis C virus (HCV) and human immunodeficiency virus 1 (HIV-1), suggesting potential roles of the s2m element in viral replication and homologous recombination events
>The secondary structure of the SARS-CoV-2 s2m element was recently solved by NMR spectroscopy and is conformationally different from that of SARS-CoVs2m
>the different nucleotide at position 31, a previously 100% conserved G in the s2m element of SARS-CoV which is mutated to U in the SARS-CoV-2 s2m, is the single driving force in the drastic difference in dimerization properties of this motif.
https://www.biorxiv.org/content/10.1101/2020.12.29.424733v1
https://www.biorxiv.org/content/10.1101/2020.12.29.424733v1.full.pdf
SARS-CoV-2 virions have been detected in the mucosa of patients with persistent SARS-2 3 months after the acute phase
https://twitter.com/doc_Moreno/status/1334518455723323394
Intact virions in the gastrointestinal tract (after 3 months)
https://www.biorxiv.org/content/10.1101/2020.11.03.367391v1
SARS-CoV-2 both D614 and G614 spike variants impair neuronal synapses and exhibit differential fusion ability
https://www.biorxiv.org/content/10.1101/2020.12.03.409763v1
"Post-infectious inflammatory disease in MIS-C features elevated cytotoxicity signatures and autoreactivity that correlates with severity"
https://www.medrxiv.org/content/10.1101/2020.12.01.20241364v1
"Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases"
https://jamanetwork.com/journals/jamacardiology/fullarticle/10.1001/jamacardio.2020.3551
Korean Study: Indoor SARS-CoV-2 Transmission from 21 Feet Away in Just 5 Minutes
https://archive.vn/2YhxN
Circulating ACE2-expressing Exosomes Block SARS-CoV-2 Virus Infection as an Innate Antiviral Mechanism
>we detected circulating exosomes that express the SARS-CoV-2 viral entry receptor angiotensin-converting enzyme 2 (ACE2) in plasma of both healthy donors and convalescent COVID-19 patients
>We demonstrated that exosomal ACE2 competes with cellular ACE2 for neutralization of SARS-CoV-2 infection. ACE2-expressing (ACE2+) exosomes blocked the binding of the viral spike (S) protein RBD to ACE2+ cells in a dose dependent manner, which was 400- to 700-fold more potent than that of vesicle-free recombinant human ACE2 extracellular domain protein (rhACE2)
>As a consequence, exosomal ACE2 prevented SARS-CoV-2 pseudotype virus tethering and infection of human host cells at a 50-150 fold higher efficacy than rhACE2.
>A similar antiviral activity of exosomal ACE2 was further demonstrated to block wild-type live SARS-CoV-2 infection.
>Of note, depletion of ACE2+ exosomes from COVID-19 patient plasma impaired the ability to block SARS-CoV-2 RBD binding to host cells
https://www.biorxiv.org/content/10.1101/2020.12.03.407031v1
SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2
>S protein alone can damage vascular endothelial cells (ECs) in vitro and in vivo, manifested by impaired mitochondrial function, decreased ACE2 expression and eNOS activity, and increased glycolysis. The underlying mechanism involves S protein downregulation of AMPK and upregulation of MDM2, causing ACE2 destabilization. Thus, the S protein-exerted vascular endothelial damage via ACE2 downregulation overrides the decreased virus infectivity
https://www.biorxiv.org/content/10.1101/2020.12.04.409144v1
https://www.biorxiv.org/content/10.1101/2020.12.04.409144v1.full.pdf
People with asthma less likely to contract SARS-2: study
https://archive.vn/K17hS
Paradoxical effects of cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) on SARS-CoV2 infection and disease
>ACE2 levels were decreased in both bronchial and alveolar epithelial cells from uninfected COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-treatment did not affect ACE2 levels but potently inhibited SARS-CoV-2 replication in this in vitro model. These findings urge to further investigate the controversial effects of CS and COPD on SARS-CoV2 infection
https://www.biorxiv.org/content/10.1101/2020.12.07.413252v1
Efficient inhibition of SARS-CoV-2 strains by a novel ACE2-IgG4-Fc fusion protein with a stabilized hinge region
>The novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) enters its host cells after binding the angiotensin-converting enzyme 2 (ACE2) via its spike glycoprotein.
>This interaction is critical for virus entry and virus-host membrane fusion.
>Soluble ACE2 ectodomains bind and neutralize the virus but the short in vivo half-lives of soluble ACE2 limits its therapeutic use.
>Fusion of the constant (Fc) part of human immunoglobulin G (IgG) to the ACE2 ectodomain can prolong the in vivo half-life but bears the risk of unwanted Fc-receptor activation and antibody-dependent disease enhancement.
>Here, we describe optimized ACE2-Fc fusion constructs that avoid Fc-receptor binding by using IgG4-Fc as a fusion partner.
>The engineered ACE2-IgG4-Fc fusion proteins described herein exhibit promising pharmaceutical properties and a broad antiviral activity at single-digit nanomolar concentration.
>In addition, they allow to maintain beneficial enzymatic activity of ACE2 and thus are very promising candidate antivirals broadly acting against coronaviruses
https://www.biorxiv.org/content/10.1101/2020.12.06.413443v1
Bioinformics study reveals P53 signaling, Genes NFKBIA, C3, CCL20 are among cellular pathways and genes affected by SARS-2.
https://www.thailandmedical.news/news/covid-19-research-bioinformatics-study-reveals-p53-signaling,-genes-nfkbia,-c3,-ccl20-are-among-cellular-pathways-and-genes-affected-by-coronavirus
SARS-CoV-2 infects cells following viral entry via clathrin-mediated endocytosis
>following engagement with the plasma membrane, SARS-CoV-2 undergoes rapid clathrin-mediated endocytosis. This suggests that transfer of viral RNA to the cell cytosol occurs from the lumen of the endosomal system, and importantly clathrin-heavy chain knockdown, which blocks clathrin-mediated endocytosis, reduces viral infectivity
https://www.biorxiv.org/content/10.1101/2020.07.13.201509v3
Neuropilin-1 helps SARS-CoV-2 get in
>short sequence from Spike attached to neuropilin-1
>SARS-CoV-2 was able to infect fewer cells if they used a small molecule called EG00229 or antibodies to block the Spike protein’s access to neuropilin-1
https://archive.vn/KtK1U
HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry
>high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacological SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible molecular connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 infection
https://archive.vn/szfXM
Ozone exposure upregulates the expression of host susceptibility protein TMPRSS2 to SARS-CoV-2
>unhealthy levels of ozone in the environment may predispose individuals to severe SARS-CoV-2 infection
>The TMPRSS2 protein and Tmprss2 transcripts were significantly elevated in the extrapulmonary airways, parenchyma, and alveolar macrophages from ozone-exposed mice. A significant proportion of additional known SARS-CoV-2 host susceptibility genes were upregulated in alveolar macrophages and parenchyma from ozone-exposed mice
https://www.biorxiv.org/content/10.1101/2020.11.10.377408v1
Targeting Lipid Rafts—A Potential Therapy for SARS-2
https://www.frontiersin.org/articles/10.3389/fimmu.2020.574508/full
Prior infection with seasonal coronavirus does not provide immunity to subsequent infection with SARS-CoV-2
>A sizable fraction of healthy blood donors have cross-reactive T cells to SARS-CoV-2 peptides due to prior infection with seasonal coronavirus. Understanding the role of cross-reactive T cells in immunity to SARS-CoV-2 has implications for managing the COVID-19 pandemic.
>We show that individuals with documented history of seasonal coronavirus have a similar SARS-CoV-2 infection rate and COVID-19 severity as those with no prior history of seasonal coronavirus.
>Our findings suggest prior infection with seasonal coronavirus does not provide immunity to subsequent infection with SARS-CoV-2
>https://www.medrxiv.org/content/10.1101/2020.12.04.20243741v1
A novel multi-omics-based identification of symptoms, comorbid conditions, and possible long-term complications in SARS-2
https://www.medrxiv.org/content/10.1101/2020.12.08.20245753v1
"SARS-CoV-2 infection associated with the recurrence of nephrotic syndrome in a 3 yea old Japanese boy"
https://archive.is/xidWr
Characterising long-term SARS-2: a rapid living systematic review
https://www.medrxiv.org/content/10.1101/2020.12.08.20246025v1
On kids-long-haulers
https://archive.vn/HbAcK
SARS-CoV-2-Associated Neurological Disorders: The Potential Route of CNS Invasion and Blood-Brain Barrier Relevance"
https://archive.vn/ISwwE
New clue to protect neurons and encourage their growth found
>Researchers know that inhibiting an enzyme called dual leucine zipper kinase (DLK) appears to robustly protect neurons in a wide range of neurodegenerative diseases models, but DLK also inhibits axonal regeneration. Until now, there have been no effective methods to modify genes to improve both the long-term survival of neurons and promote regeneration.
>researchers identified another family of enzymes called germinal cell kinase four kinases (GCK-IV kinases) whose inhibition is robustly neuroprotective, while also permitting axon regeneration, making it an attractive therapeutic approach for treating at some neurodegenerative diseases
https://archive.vn/mXhUk
LL-37 fights SARS-CoV-2: The Vitamin D-Inducible Peptide LL-37 Inhibits Binding of SARS-CoV-2 Spike Protein to its Cellular Receptor Angiotensin Converting Enzyme 2 In Vitro
>We have revealed a biochemical link between vitamin D, LL-37, and COVID-19 severity. SPR analysis demonstrated that LL-37 binds to SARS-CoV-2 S protein and inhibits binding to its receptor hACE2, and most likely viral entry into the cell. This study supports the prophylactic use of vitamin D to induce LL-37 that protects from SARS-CoV-2 infection, and the therapeutic administration of vitamin D for the treatment of COVID-19 patients. Further, our results provide evidence that the direct use of LL-37 by inhalation and systemic application may reduce the severity of COVID-19
https://www.biorxiv.org/content/10.1101/2020.12.02.408153v1
SARS-CoV-2 Requires Cholesterol for Viral Entry and Pathological Syncytia Formation
>Many enveloped viruses induce multinucleated cells (syncytia), reflective of membrane fusion events caused by the same machinery that underlies viral entry. These syncytia are thought to facilitate replication and evasion of the host immune response. Here, we report that co-culture of human cells expressing the receptor ACE2 with cells expressing SARS-CoV-2 spike, results in synapse-like intercellular contacts that initiate cell-cell fusion, producing syncytia resembling those we identify in lungs of COVID-19 patients. To assess the mechanism of spike/ACE2-driven membrane fusion, we developed a microscopy-based, cell-cell fusion assay to screen ~6000 drugs and >30 spike variants. Together with cell biological and biophysical approaches, the screen reveals an essential role for membrane cholesterol in spike-mediated fusion, which extends to replication-competent SARS-CoV-2 isolates
https://www.biorxiv.org/content/10.1101/2020.12.14.422737v1
Viral persistence in the olfactory epithelium therefore provides a potential mechanism for prolonged or relapsing symptoms of SARS-2
https://www.biorxiv.org/content/10.1101/2020.11.18.388819v1
Strong selection on SARS-CoV-2 during convalescent plasma therapy associated with emergence of viral variants with reduced susceptibility to neutralising antibodies
>we report chronic SARS-CoV-2 with reduced sensitivity to nAb in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences by both short and long read technologies over 23 time points spanning 101 days. Although little change was observed in the overall viral population structure following two courses of remdesivir over the first 57 days, N501Y in Spike was transiently detected at day 55 and V157L in RdRp emerged.
>following convalescent plasma we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 N-terminal domain NTD of the Spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma
>In vitro, the Spike escape double mutant bearing ΔH69/ΔV70 and D796H conferred decreased sensitivity to convalescent plasma, whilst maintaining infectivity similar to wild type. D796H appeared to be the main contributor to decreased susceptibility, but incurred an infectivity defect. The ΔH69/ΔV70 single mutant had two-fold higher infectivity compared to wild type and appeared to compensate for the reduced infectivity of D796H. Consistent with the observed mutations being outside the RBD, mAb targeting the RBD were not impacted by either or both mutations, but a non RBD binding mAb was less potent against ΔH69/ΔV70 and the double mutant
https://www.medrxiv.org/content/10.1101/2020.12.05.20241927v3
[chink study, but something that SARS-CoV-1 does through its nucleocapsid...]
>Although none of the SARS-CoV proteins was found to be directly bound to HAb18G/CD147, the nucleocapsid (N) protein of SARS-CoV was bound to CyPA, which interacted with HAb18G/CD147
https://academic.oup.com/jid/article/191/5/755/1238824
[...SARS-CoV-2 does through spike protein???] CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells
>we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment
>[!] Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice [!]
>Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient
>Furthermore, CD147 mediates virus entering host cells by endocytosis
https://archive.vn/VGKLB
[Also, CyPA is involved in SARS-CoV-2 indeed]
>Alisporivir, which is a non-immunosuppressive CyPA inhibitor, was reported to reduce SARS-CoV-2 RNA production in vitro
[bonus confirmation on N protein in SARS-CoV-1 and S protein in SARS-CoV-2]
>blocking CD147 on host cells shows inhibition on SARS-CoV-2 and that CD147 has a critical role in promoting the infection of host cells by the virus. Surface plasmon resonance by using Biacore analysis confirmed the interaction between CD147 and S protein (SP) [17]. In earlier studies, mediated through CyPA bound to N protein of SARS-CoV, CD147 plays a role in facilitating infection of host cells by SARS-CoV
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364167
[And also]
>One key feature of SARS-CoV-2 is the presence of an enigmatic insertion in the spike glycoprotein gene representing a novel multibasic S1/S2 protease cleavage site
https://www.sciencedirect.com/science/article/pii/S2590152420300209
[So?]
1 year ago pajeets found that SARS-CoV-2 spike protein aligned with HIV-1 Gag very well
https://www.biorxiv.org/content/10.1101/2020.01.30.927871v1.full
HIV
>Gag Proteins
>The cleavage of the Gag precursor protein (p55) by viral protease (PR) during the process of viral maturation results in three principal proteins: matrix (MA/p17), capsid (CA/p24), and nucleocapsid (NC/p7).
>The CA (p24) protein sequentially follows MA in the p55 precursor protein. In the mature virion, CA forms the shell of the core, which is occasionally tubular but most often conical, a feature that distinguishes lentiviruses such as HIV-1 from most other retroviruses. It also has crucial roles in particle assembly by binding the cellular cyclophilins in steps following HIV entry into a new target cell.
>majority of the p24 capsid protein (> 90%) is associated with HIV-1 particles
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/p24-capsid-protein
[!]
>Viral incorporation of cyclophilin A (CyPA) during the assembly of human immunodeficiency virus type-1 (HIV-1) is crucial for efficient viral replication. CyPA binds to the previously identified Gly-Pro90 site of the capsid protein p24
https://pubmed.ncbi.nlm.nih.gov/10026140
[Just a coincidence bro?]
False positive on p24 antigen test
>Cross-reactivity of SARS-CoV-2 with HIV chemiluminescent assay leading to false-positive results
https://jcp.bmj.com/content/early/2020/09/08/jclinpath-2020-206942
[Less relevant, but worth mentioning]
HIV-1 protease cleaves Gag
https://en.wikipedia.org/wiki/HIV-1_protease
[old USA study, with some Slav names] CD147 facilitates HIV-1 infection by interacting with virus-associated cyclophilin A (CyPA)
>a small portion of viral CyPA is accessible for protease cleavage and thus should extend outside of the viral membrane
https://archive.vn/5F90y
Sharing CD4+ T Cell Loss: When SARS-2 and HIV Collide on Immune System
>COVID-19 is a distinctive infection characterized by elevated inter-human transmission and presenting from absence of symptoms to severe cytokine storm that can lead to dismal prognosis
>Like for HIV, lymphopenia and drastic reduction of CD4+ T cell counts in COVID-19 patients have been linked with poor clinical outcome
>As CD4+ T cells play a critical role in orchestrating responses against viral infections, important lessons can be drawn by comparing T cell response in COVID-19 and in HIV infection and by studying HIV-infected patients who became infected by SARS-CoV-2
>Both HIV-1 and SARS-CoV-2 infection share CD4+ T cell loss in association with disease outcome and immunodeficiency
>Direct attacks on CD4+ T cells, immune activation and redistribution of CD4+ T cell are contributing mechanisms in very different proportion for CD4+ T cell lymphopenia in both diseases
>During the period of immunodeficiency, systemic inflammation could be fueled by leaky gut and lead to severe complications
>When HIV meets COVID-19, no increase in the occurrence of COVID-19 and no excess morbidity and mortality among PLWH with symptomatic COVID-19 has been reported
>IL-7 and IL-2 were previously used to increase CD4+ T cell counts in HIV-1 infection, however, no improvement in their function were reported
>As CD4+ T cells orchestrate immune responses, proper CD4+ T cell function is required for effective vaccine responses
>Hence, anti-SARS-CoV-2 antibodies and CD4 responses should be studied in order to develop long-term efficiency vaccine formulation. Overall, experience in HIV clinical management and past clinical trials represent a special use case for innovative studies aiming at increasing CD4+ T cell function and reducing COVID-19 morbidity
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770166
Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection
>we examined immune cell subsets in hospitalized and non-hospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared to healthy and convalescent individuals, with the exception of B lymphocytes which increased
>Our findings show increased frequencies of T-cell activation markers (CD69, Ox40, HLA-DR and CD154) in hospitalized patients, with other T-cell activation/exhaustion markers (CD25, PD-L1 and TIGIT) remaining elevated in hospitalized and non-hospitalized individuals
>B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization, followed by an increase in PD1 frequencies in non-hospitalized individuals
>Interestingly, many of these changes were found to increase over time in non-hospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation following SARS-CoV-2 infection
>Changes in T-cell activation/exhaustion in non-hospitalized patients were found to positively correlate with age.
>Severely infected individuals had increased expression of activation and exhaustion markers.
>These data suggest a prolonged period of immune dysregulation following SARS-CoV-2 infection highlighting the need for additional studies investigating immune dysregulation in convalescent individuals
https://www.jci.org/articles/view/140491/pdf
Peripheral and lung resident T cell responses against SARS-CoV-2
>SARS-CoV-2 viral load positively correlated with the overall capacity of CD4+ T cells to secrete IL-4 in response to TCR independent unspecific activation with PMA/ionomycin.
>Correlations between the net frequency of a given function and clinical parameters were consistent with more CD4+T cells secreting IFNg and more CD8+ T cells secreting IL-4 in response to M and S peptides associated with disease severity .
>Even the total CD4+ or CD8+ T cell IFNg response and the total IL-4 secretion by CD8+ T cells against any of the three viral proteins (all peptides) correlated with more days at the hospital for IFNg or with other clinical parameters for IL-4.
>Further, antigen-specific CD4+ T cells degranulating in response to all viral peptides and, in the case of CD8+ T cells, in response to M peptides also correlated with higher levels of IL-6.
>In contrast, the percentage of M-specific CD4+ T cells secreting IL-10 correlated with better prognosis in all clinical parameters and for N-specific positively with better oxygenation at 48h.
>Regarding antigen-specific T cells we detected remarkable differences within the IL-10 secreting T cells.
>In this sense, increased expression of caspase-3 was distinguished in the hospitalized severe group compared to the non-hospitalized in S-specific IL-10+ CD4+ T cells, N-specific IL-10+ CD8+ T cells and even in the overall IL-10 secretion capacity in response to PMA/Io response.
https://www.medrxiv.org/content/10.1101/2020.12.02.20238907v2
Small Number of SARS-2 Patients Develop Severe Psychotic Symptoms
>Physically, most of these patients didn’t get very sick from Covid-19. The patients experienced no respiratory problems, but
>they did have subtle neurological symptoms like hand tingling, vertigo, headaches or diminished smell.
>Then, two weeks to several months later, they “develop this profound psychosis, which is really dangerous and scary to all of the people around them.”
>Also striking is that most patients have been in their 30s, 40s and 50s.
>“It’s very rare for you to develop this type of psychosis in this age range,” since such symptoms more typically accompany schizophrenia in young people or dementia in older patients.
>And some patients understood something was wrong, while usually “people with psychosis don’t have an insight that they’ve lost touch with reality.”
>A neurovirology expert, said that although people might recover physically from Covid-19, in some cases their immune systems, might be unable to shut down or might remain engaged because of “delayed clearance of a small amount of virus.”
>Persistent immune activation is also a leading explanation for brain fog and memory problems bedeviling many Covid survivors, a schizophrenia expert said post-Covid cognitive and psychiatric effects might result from something similar happening in the brain.
>It may hinge on which brain region the immune response affects, some people have neurological symptoms, some people psychiatric and many people have a combination.
>Experts don’t know whether genetic makeup or an undetected predisposition for psychiatric illness put some people at greater risk.
>Sporadic cases of post-infectious psychosis and mania have occurred with other viruses, 1918 flu and SARS and MERS.
>The symptoms have ranged widely, some surprisingly severe for a first psychotic episode, experts said
https://archive.vn/BoiS2
Patterns of within-host genetic diversity in SARS-CoV-2
>Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within and between host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection
https://www.biorxiv.org/content/10.1101/2020.12.23.424229v1
The SARS-CoV-2 S1 spike protein mutation N501Y alters the protein interactions with both hACE2 and human derived antibody: A Free energy of perturbation study
>we observed significant decrease of the binding between S1 RBD and STE90-C11 antibody by ΔΔG of 3.78kcal/mol.
>Thus, our calculations predict that the N501Y mutant will produce a decrease of the binding to ΔG=-8.92kcal/mol or 293nM.
>This is about 161 times lower than the wild type.
https://www.biorxiv.org/content/10.1101/2020.12.23.424283v1
A summary of the different ways of tallying excess deaths:
>Whatever metric you choose, Latin America has been hit extremely hard. Europe next hardest-hit, though with very different outcomes from place to place."
https://archive.vn/RXyRm
Large regional differences in corona mortality
>3 prefectures including Iwate are over 5%, Tokyo 1%"
https://archive.vn/tmTsH
Māori and Pacific People in New Zealand have higher risk of hospitalisation for SARS-2
>We used data on age, ethnicity, deprivation index, pre-existing health conditions, and clinical outcomes on 1,829 COVID-19 cases reported in New Zealand. We used a logistic regression model to calculate odds ratios for the risk of hospitalisation by ethnicity. We also consider length of hospital stay and risk of fatality
>Māori have 2.5 times greater odds of hospitalisation than non-Māori, non-Pacific people, after controlling for age and pre-existing conditions. Similarly, Pacific people have 3 times greater odds
>Deprivation index was only statistically significant when considered alongside age but not ethnicity. Deprivation index and ethnicity were slightly correlated, so this suggests the effect of deprivation index was partially captured by ethnicity. Different age groups were represented differently across different levels of deprivation index, suggesting a model containing a deprivation index-age interaction term may be suitable. This was tested and the resulting coefficients were not statistically significant.
>In the 1,829 cases in the data, there was only a very small correlation between having underlying conditions recorded and either Māori ethnicity or Pacific ethnicity
https://www.medrxiv.org/content/10.1101/2020.12.25.20248427v1
Disruption of nasal bacteria enhances protective immune responses to influenza A virus and SARS-CoV-2 infection in mice
>while intranasal administration of influenza virus hemagglutinin vaccine alone was insufficient to induce the vaccine-specific antibody responses, disruption of nasal bacteria by lysozyme or addition of culturable oral bacteria from a healthy human volunteer rescued inability of the nasal bacteria to generate antibody responses to intranasally administered the split-virus vaccine.
>Myd88-dependent signaling in the hematopoietic compartment was required for adjuvant activity of intranasally administered oral bacteria.
>In addition, we found that the oral bacteria-combined intranasal vaccine induced protective antibody response to influenza virus and SARS-CoV-2 infection.
>Our findings here have identified a previously unappreciated role for nasal bacteria in the induction of the virus-specific adaptive immune responses
https://www.biorxiv.org/content/10.1101/2020.12.25.424300v1
Quantitative evaluation and progress of olfactory dysfunction in SARS-2
>Patients who described new-onset olfactory dysfunction, who were treated in the COVID-19 departments of our hospital and whose PCR tests demonstrated SARS-CoV-2 presence were included in the study and they were investigated prospectively. Clinical information of all the patients was taken and the levels of olfactory function were detected using the Brief Smell Identification Test (BSIT). Scores equal to or below 8 are considered as olfactory dysfunction. Patients who were followed up for 3 months were reevaluated with the BSIT test at the end of the third month and the progression of the symptom was investigated
>Results: The mean BSIT test score of the 42 patients (23 female patients, 19 male patients, mean age: 41.2 ± 14.6) was 5.2 ± 2.2. There was severe olfactory dysfunction in 16.7% of the patients (0-2 points), moderate olfactory dysfunction in 31% (3-5 points), and mild olfactory dysfunction in 52.4% (6-8 points). After a follow-up for 3 months, full recovery was observed in 36 patients (85.7%) and the mean test score rose to 9.9 ± 1.8. Although olfactory dysfunction persisted in 6 patients, an elevation in test scores was noted. Olfactory dysfunction was the first symptom in 17 patients (40%) and the other symptoms occurred after 2 days (1-6) on average
https://pubmed.ncbi.nlm.nih.gov/33385250
>individuals with higher levels of coronaphobia may also have higher levels of state anxiety or vice versa. Further, we found a multivariate difference in coronaphobia between men and women
https://pubmed.ncbi.nlm.nih.gov/33385190
Proton Pump Inhibitors use is not associated with increased risk infection and may not change the mortality risk of SARS-2 but appeared to be associated with increased risk of progression to severe disease and secondary infection
https://www.medrxiv.org/content/10.1101/2020.12.25.20248860v1
Engineering, production and characterization of Spike and Nucleocapsid structural proteins of SARS–CoV-2 in Nicotiana benthamiana as vaccine candidates against SARS-2
>we engineered the Nucleocapsid (N) and Spike protein (S) variants (Receptor binding domain, RBD and S1 domain) of SARS-CoV-2 genes and produced in Nicotiana benthamiana plant.
>The purification yields were at least 20 mg of pure protein/kg of plant biomass for each target protein. The S protein variants of SARS-CoV-2 showed specific binding to angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 receptor
>The purified plant produced N and S variants were recognized by N and S protein specific monoclonal and polyclonal antibodies demonstrating specific reactivity of mAb to plant produced N and S protein variants
>In addition, IgG responses of plant produced N and S antigens elicited significantly high titers of antibody in mice. This is the first report demonstrating production of functional active S1 domain and Nucleocapsid protein of SARC-CoV-2 in plants. In addition, in this study, for the first time, we report the co-expression of RBD with N protein to produce a cocktail antigen of SARS-CoV-2, which elicited high-titer antibodies compared to RBD or N proteins
https://www.biorxiv.org/content/10.1101/2020.12.29.424779v1
[chink study with chink datasets, careful] Cell-cell interactions are significantly different in SARS-2 patients
>in healthy controls, most cell-cell interactions are between basal, ciliated, and goblet cells of the lung epithelium, with dendritic cells providing immune surveillance. As disease severity increases, cell-cell interactions become dominated by interactions between the lung epithelium and proinflammatory players within the immune compartment.
>in monocyte-related interactions, COVID-19 patients generally have more cell-cell interactions than healthy controls
>Reduced T cell interactions and increased monocyte interactions in severe COVID-19 patients across different compartments
>higher interactions between monocyte/macrophage or T cells towards neutrophils in severe patients
>severe patients have a decrease in CD8 memory T cell interactions. The lack of T cell interactions in severe patients suggests potential T cell depletion,
>Monocyte/macrophage and neutrophil interaction in severe patients are dominated by IL1B, IL1RN, IL8, TNFRSF1B, CCL4, IFIT2, IFIT3, CCL8, CXCL10, CXCL11, CCL2, CXCL1, CXCL2 and CXCL5 and other inflammation pathways
>Interaction from goblet cells to immune cells are heterogeneous in moderate patients and severe patients
>Cell-cell interaction patterns have the potential to discriminate between moderate and severe patients
https://www.biorxiv.org/content/10.1101/2020.12.30.424641v1.full.pdf
[Read the full, can't fit it all in high-lights] Meta-analysis of virus-induced host gene expression reveals unique signatures of immune dysregulation induced by SARS-CoV-2
>In order to better understand the immune dysregulation induced by SARS-CoV-2, we carried out a meta-analysis of these transcriptomics data available in the published literature.
>Datasets included both those available from SARS-CoV-2 infected cell lines in vitro and those from patient samples.
>We focused our analysis on the identification of viral perturbed host functions as captured by co-expressed gene module analysis.
>Transcriptomics data from lung biopsies and nasopharyngeal samples, as opposed to those available from other clinical samples and infected cell lines, provided key signatures on the role of the host's immune response on COVID-19 pathogenesis.
>For example, severity of infection and patients' age are linked to the absence of stimulation of the RIG-I-like receptor signaling pathway, a known critical immediate line of defense against RNA viral infections that triggers type-I interferon responses.
>In addition, co-expression analysis of age-stratified transcriptional data provided evidence that signatures of key immune response pathways are perturbed in older COVID-19 patients.
>In particular, dysregulation of antigen-presenting components, down-regulation of cell cycle mechanisms and signatures of hyper-enriched monocytes were strongly correlated with the age of older individuals infected with SARS-CoV-2
https://www.biorxiv.org/content/10.1101/2020.12.29.424739v1
https://www.biorxiv.org/content/10.1101/2020.12.29.424739v1.full.pdf
In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in SARS-2
>we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs
>We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease
>Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drug combinations on inflammatory cytokine production in peripheral blood mononuclear cells, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production
https://www.biorxiv.org/content/10.1101/2020.12.29.424728v1
SARS-CoV-2 spike glycoprotein S1 induces neuroinflammation in BV-2 microglia
(Microglial cells are the resident macrophages of the central nervous system)
>we investigated the effects of the SARS‐CoV‐2 spike glycoprotein S1 stimulation on neuroinflammation in BV-2 microglia
>Analyses of culture supernatants revealed an increase in the production of TNFα, IL-6, IL-1β and iNOS/NO. SARS‐CoV‐2 spike glycoprotein S1 increased protein expressions of phospho-p65 and phospho-IκB, as well as enhancing DNA binding and transcriptional activity of NF-κB.
>Pro-inflammatory effects of the glycoprotein effects were reduced in the presence of BAY11-7082 (1 μM).
>The presence of SARS‐CoV‐2 spike glycoprotein S1 in BV-2 microglia increased the protein expression of NLRP3, as well as caspase-1 activity. However, pre-treatment with CRID3 (1 μM) or BAY11-7082 (1 μM) resulted in the inhibition of NLRP3 inflammasome/caspase-1.
>It was also observed that CRID3 attenuated SARS‐CoV‐2 spike glycoprotein S1-induced increase in IL-1β production. Increased protein expression of p38 MAPK was observed in BV-2 microglia stimulated with the spike glycoprotein S1, and was reduced in the presence of SKF 86002.
>results have provided the first evidence demonstrating SARS-CoV-2 spike S1 glycoprotein-induced neuroinflammation in BV-2 microglia
>promotion of neuroinflammation by this glycoprotein is mediated through activation of NF-κB, NLRP3 inflammasome and p38 MAPK. These results are significant because of their relevance to our understanding of neurological and neuropsychiatric symptoms observed in patients infected with SARS-CoV-2.
https://www.biorxiv.org/content/10.1101/2020.12.29.424619v1
>At this moment 1 year ago, China's health commission released the first official statement about 27 cases with unexplained pneumonia, which we now know as SARS-2. It was deleted but can be found here
https://web.archive.org/web/20200106064908/http://wjw.wuhan.gov.cn/front/web/showDetail/2019123108989
Microvascular Injury in the Brains of Patients with SARS-2
>In a convenience sample of patients who had died from Covid-19, multifocal microvascular injury was observed in the brain and olfactory bulbs by means of magnetic resonance microscopy, histopathological evaluation, and immunohistochemical analysis of corresponding sections, without evidence of viral infection. These findings may inform the interpretation of changes observed on magnetic resonance imaging of punctate hyperintensities and linear hypointensities in patients with Covid-19.
https://archive.vn/LVg6F
>A rare, but troubling side effect of COVID-19 has been noted by psychiatric experts across the country. People with no previous history of mental illness are showing signs of severe psychosis after becoming infected with the virus. Dr. Hisam Goueli, a psychiatrist at South Oaks Hospital in New York, recalls treating one such woman who said she kept seeing her children murdered and had plans to kill them herself. She had contracted COVID-19 last spring and Goueli wondered if there could be a connection.
>Then, according to The New York Times, he began treating other patients with similar signs and medical history. “There’s something happening,” he thought. The pattern of COVID-19 induced psychosis was noted in a British study. Researchers found that out of 153 hospitalized patients with coronavirus, 10 of them developed psychosis. A similar finding was noted in Spain.
https://archive.vn/gDqLR
[Sleep and SARS-2 section]
>ACE2 functions as a negative regulator of the RAS by cleaving ATII at its C-terminus and creating vasodilating angiotensin 1–7 (Ang(1–7))
>Possible circadian changes in the expression of ACE2 in the lungs have not been reported until now, but ATII is known to affect the rhythmic expression of Per2, one of the key repressors that constitutes the feedback loop of mammalian clock circuitry in the suprachiasmatic nuclei
>levels of ACE expression in the heart show distinct diurnal changes and ATII induces changes in the expression of circadian genes in the vascular cells, while changes in BMAL1 expression also affect the expression of angiotensinogen and resting blood pressure in perivascular adipose tissues
>lung expression of ACE2 will also manifest circadian changes through cell autonomous regulations and through indirect effects of circadian changes in the RAS
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191115
[]
Interdependence of nutrient metabolism and the circadian clock system: Importance for metabolic health
>A number of circadian clock proteins as well as their accessory proteins (such as nuclear receptors) are highly sensitive to nutrient metabolism. Macronutrients and micronutrients can function as zeitgebers for the clock in a tissue-specific way and can thus impair synchrony between clocks across the body, or potentially restore synchrony in the case of circadian misalignment. Circadian nuclear receptors are particularly sensitive to nutrient metabolism and can alter tissue-specific rhythms in response to changes in the diet. SNPs in human clock genes appear to be correlated with diet-specific responses and along with chronotype eventually may provide valuable information from a clinical perspective on how to use diet and nutrition to treat metabolic disorders
https://www.sciencedirect.com/science/article/pii/S2212877815002367
https://www.huffpost.com/entry/dopamine-sleep-regulation-melatonin-norepinephrine_n_1609964
https://parkinsonviewpoint.com/the-role-of-melatonin-in-parkinsons-disease/
[Sleep and SARS-2 section]
The Stanford Hall consensus statement for post-SARS-2 rehabilitation
>Psychological rehabilitation recommendations:
>Individuals should be reviewed in the recovery phase to identify those who may have adverse psychological outcomes as a result of their COVID-19 experiences. Healthcare workers who contracted COVID-19 should be considered a high-risk group.
>Active monitoring (ongoing review) should be undertaken for those with subthreshold psychological symptoms.
>Referral to psychological services and consideration of trauma focused cognitive behavioural therapy, cognitive processing therapy or eye movement desensitisation and reprocessing is appropriate for those with moderate to severe symptoms of acute stress disorder.
>Neurological rehabilitation recommendations:
>All patients with COVID-19 should be reviewed for any neurological symptoms, as symptoms can be immediate (at time of active infection) or delayed (in the weeks following COVID-19). Consider a cognitive screen for those at risk (postcritical care or with residual cognitive impairment).
>Reassurance should be given that milder neurological symptoms like headache, dizziness, loss of smell or taste, and sensory changes are likely to improve with minimal intervention. Level of evidence
>Education should be provided that mild-to-moderate neurological symptoms are likely to have a full recovery.
>Severe symptoms potentially may result in significant or life-changing impairment, therefore inpatient multidisciplinary rehabilitation is recommended for patients with moderate-to-severe neurological symptoms to maximise recovery.
>Medical rehabilitation recommendations:
>In post-COVID-19 patients with new-onset shortness of breath or chest pain, life-threatening medical complications should be considered.
https://pubmed.ncbi.nlm.nih.gov/32475821/
SARS-CoV-2 Uses CD4 to Infect T Helper Lymphocytes
>Here we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients
>We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells in a mechanism that also requires ACE2 and TMPRSS2
>Once inside T helper cells, SARS-CoV-2 assembles viral factories, impairs cell function and may cause cell death. SARS-CoV-2 infected T helper cells express higher amounts of IL-10, which is associated with viral persistence and disease severity
>Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may explain the poor adaptive immune response of many COVID- 19 patients
https://www.medrxiv.org/content/10.1101/2020.09.25.20200329v1
Monocular visual loss - first case of central retinal artery occlusion (CRAO) as the initial manifestation of SARS-2 infection
>the hypercoagulable state caused by virus-induced cytokine storm likely triggered the formation of the internal carotid artery thrombus that led to a CRAO
>CRAO causes retinal ischemia, and prompt medical treatment is warranted to prevent irreversible retinal cell death and ultimately blindness. The retinal cells can sustain ischemic conditions for approximately 2 h;beyond that window the damage may be irreversible. Hyperbaric oxygen therapy (HBOT) may be used as an adjunct to thrombolytic treatment [12].
>In retrospective studies, critically-ill COVID-19 patients had increased proinflammatory cytokines, including interleukin 2 (IL-2) and tumor necrosis factor α4 (TNF-α4), which can upregulate the coagulation system
>In this case, visual loss occurred secondary to occlusion of the internal carotid artery extending into the skull base. The clinical findings were consistent with a CRAO rather than ophthalmic artery (OA) occlusion, either because of partial backfilling of the OA from the posterior communicating artery or secondary to an embolism from the carotid artery thrombus lodged in the central retinal artery posterior to the lamina cribrosa; in this case, partial occlusion of the OA cannot be rules out. Hemispheric stroke was averted because of reperfusion of the ICA at the level of the anterior clinoid process.
https://www.sciencedirect.com/science/article/pii/S0303846720307836
[The referenced case reports are from china, but the theory/explanations are from Indians] Eyes Have It: From SARS-2 Perspective
>abundance of ACE2 receptors on the ocular surface makes them a prospective target of COVID-19. However, the accumulation of SARS-CoV-2 in ophthalmic secretions remains unclear. Probably due to direct inoculation by the aerosolized viral particles, transmission from the nasopharynx through the nasolacrimal duct
>In animal studies, coronaviruses have been associated with anterior uveitis, retinitis, vasculitis, and optic neuritis.5 Seventeen percent of human coronavirus NL 63 (HCoV-NL63) are found to be associated with conjunctivitis
>ocular surface infection is a potentially dangerous route of transmission, and healthcare professionals should be cautious in this regard. Further research on ophthalmological manifestation, viral transmission through ocular secretions, long-term complications of these patients is the need of the hour
[dosage details in link]
>Ocular side effects of different trial drugs for COVID-19
>Hydroxychloroquine - Vortex keratopathy, maculopathy
>Ivermectin - Foreign body sensation, eyelid edema, anterior uveitis, blurred
>Tocilizumab - Retinopathy
>Ritonavir/lopinavir - Blurring of vision, toxic epidermal necrolysis
>Favipiravir - Blurring of vision, ocular pain, toxic epidermal necrolysis, Stevens–Johnson syndrome
>Methylprednisolone - Ocular hypertension, posterior subcapsular cataract, open-angle glaucoma
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751054/
Ethnicity and the relationship between SARS-2 and the herpes simplex viruses
>Non-Hispanic black, Mexican American and other Hispanic participants had a mean pathogen 1.3-1.9 times that of non-Hispanic Whites
>Herpes simplex virus type 1 can inactivate most of the elements in the immune system, that are designed to protect against the incursions of viruses, bacteria and other pathogens. HSV-1 can also damage the blood brain barrier (BBB), which prevents the entry of pathogens into the central nervous system. Without the help of HSV-1, the COVID-19 virus may not be able to cause serious illness or death in humans
https://www.sciencedirect.com/science/article/pii/S0306987720333387
[chink study, but the topic is worth additional lurking IMO] Key components of inflammasome and pyroptosis pathways are deficient in canines and felines, possibly affecting their response to SARS-CoV-2 infection
https://www.frontiersin.org/articles/10.3389/fimmu.2020.592622/abstract
[Diabetes section]
SARS-CoV-2 Infection Presenting with Hyperglycemia and Ketosis: A Case Series of Three Diabetic Patients
>excessive hyperglycemia and ketosis may manifest in diabetic patients with COVID-19 and the emergency and intensive care physicians should measure blood sugar and ketone levels on presentation in all diabetic patients and be careful about fluid management
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751029
[]
New-Onset Diabetes in SARS-2: Time to Frame Its Fearful Symmetry
>There is increasing evidence that coronavirus disease 2019 (COVID-19) may lead to new-onset diabetes mellitus (DM). This may occur even in patients without predisposing factors for impaired glucose metabolism. Both impaired pancreatic insulin secretion and insulin resistance have been implicated as underlying mechanisms. Importantly, new-onset hyperglycaemia is associated with worse prognosis in patients with COVID-19. Indeed, its prognosis may be even more sinister than in patients with pre-existing DM. More research data and knowledge are currently being collected to improve our insights into this constellation and to guide therapies in clinical reality.
https://archive.vn/0jEjV
[]
New onset diabetes, type 1 diabetes and SARS-2
>Past lessons and new data teach us that severe acute respiratory syndrome coronaviruses (SARS-CoV and SARS-CoV-2) can enter islet cells via angiotensin converting enzyme-2 (ACE-2) receptors and cause reversible β-cell damage and transient hyperglycemia. There have been postulations regarding the potential new-onset T1DM triggered by COVID-19. This article reviews the available evidence regarding the impact and interlink between COVID-19 and Τ1DM. We also explore the mechanisms behind the viral etiology of Τ1DM.
>SARS-CoV-2 can trigger severe diabetic ketoacidosis at presentation in individuals with new-onset diabetes. However, at present, there is no hard evidence that SARS-CoV-2 induces T1DM on it’s own accord. Long term follow-up of children and adults presenting with new-onset diabetes during this pandemic is required to fully understand the type of diabetes induced by COVID-19.
https://archive.vn/ml1l7
[]
An Immediate and Long-Term Complication of SARS-2 May Be Type 2 Diabetes Mellitus
https://archive.vn/ISwwE
[Diabetes section]
Analysis of 240,392 patients hospitalized with SARS-2
> Use of dialysis, tracheostomy, and extracorporeal membrane oxygenation among 240,392 patients hospitalized with COVID-19 in the United States
> 9,703 (4.04% [95% CI: 3.96% to 4.11%]) patients received dialysis
> 1,681 (0.70% [0.67% to 0.73%]) had a tracheostomy
> 398 (0.17% [95% CI: 0.15% to 0.18%]) patients underwent ECMO
> over the 30 days following hospitalization
https://www.medrxiv.org/content/10.1101/2020.11.25.20229088v1
BioLAGO member myPOLS GmbH succeeds in SARS-CoV-2 RT-PCR detection without RNA extraction
https://www.biolago.org/2020/11/30/biolago-mitglied-mypols-gmbh-gelingt-sars-cov-2-rt-pcr-nachweis-ohne-rna-extraktion/
Integrated genome-scale metabolic model of normal human bronchial epithelial cells (NHBE) infected with SARS Cov2 using gene-expression and macromolecular make-up of the virus. The reconstructed model predicts growth rates of the virus in high agreement with the experimental measured values. Furthermore, we report a method for conducting genome-scale differential flux analysis (GS-DFA) in context-specific metabolic models.
>several enzymes driving the altered reactions inferred by our method to be directly interacting with viral proteins and also undergoing differential phosphorylation under diseased state. In case of SARS Cov2 infection, lipid metabolism particularly fatty acid oxidation and beta-oxidation cycle along with arachidonic acid metabolism are predicted to be most affected which confirms with clinical metabolomics studies.
https://www.biorxiv.org/content/10.1101/2020.11.29.402404v1
HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry
>S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacological SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues
https://archive.vn/szfXM
Recombinant Fc-fusion vaccine of RBD induced protection against SARS-CoV-2 in non-human primate and mice
>Here we developed a pilot scale production of a recombinant subunit vaccine (RBD-Fc Vacc) with the Receptor Binding Domain of SARS-CoV-2 S protein fused with the Fc domain of human IgG1. RBD-Fc Vacc induced SARS-CoV-2 specific neutralizing antibodies in non-human primates and human ACE2 transgenic mice. The antibodies induced in macaca fascicularis neutralized three divergent SARS-CoV2 strains, suggesting a broader neutralizing ability. Three times immunizations protected Macaca fascicularis (20ug or 40ug per dose) and mice (10ug or 20ug per dose) from SARS-CoV-2 infection respectively. These data support clinical development of SARS-CoV-2 vaccines for humans. RBD-Fc Vacc is currently being assessed in randomized controlled phase 1/II human clinical trails
https://www.biorxiv.org/content/10.1101/2020.11.29.402339v1
Change of dominant strain during dual SARS-CoV-2 infection
>>Our findings suggest that the patient was infected by two genetically distinct SARS-CoV-2 strains at the same time. One of the possible explanations is that the second infection occurred in the hospital
https://www.medrxiv.org/content/10.1101/2020.11.29.20238402v1
A new study says that chemical compounds from green tea, two varieties of muscadine grapes, cacao powder, and dark chocolate were able to bind to a particular enzyme, or protease, in the virus and stop it reproducing
https://archive.vn/9Xzic
Docking Characterization and in vitro Inhibitory Activity of Flavan-3-ols and Dimeric Proanthocyanidins Against the Main Protease Activity of SARS-Cov-2
>To further substantiate the inhibitory activities, extracts prepared from green tea (GT), two muscadine grapes (MG), cacao, and dark chocolate (DC), which are rich in CAG, ECG, GAG, EGCG, or/and PB2, were used for inhibitory assay. The resulting data showed that GT, two MG, cacao, and DC extracts inhibited the Mpro activity with an IC50 value, 2.84 ± 0.25, 29.54 ± 0.41, 29.93 ± 0.83, 153.3 ± 47.3, and 256.39 ± 66.3 μg/ml, respectively. These findings indicate that on the one hand, the structural features of flavan-3-ols are closely associated with the affinity scores; on the other hand, the galloylation and oligomeric types of flavan-3-ols are critical in creating the inhibitory activity against the Mpro activity.
https://archive.vn/g7Izq
Longitudinal multi-omics analyses identify responses of megakaryocytes, erythroid cells and plasmablasts as hallmarks of severe SARS-2 trajectories
>SARS-CoV2 infection elicits dynamic changes of circulating cells in the blood
>Severe COVID-19 is characterized by increased metabolically active plasmablasts
>Elevation of IFN-activated megakaryocytes and erythroid cells in severe COVID-19
>Cell-type specific expression signatures are associated with a fatal COVID-19 outcome
https://archive.vn/XUfW6
Asymptomatic patients have higher SARS-CoV-2 viral loads than symptomatic patients, study says
>researchers collected nasopharyngeal, oropharyngeal, oral cavity, rectal, saliva, urine, and blood samples from patients who were hospitalized due to COVID-19.
>A total of 360 samples from 60 patients were obtained upon admission. Of these, 25 percent did not have symptoms, while 75 percent were symptomatic.
>The Public Health Institute of Turkey Virology Reference and Research Laboratory analyzed the samples.
>The researchers found that vital loads of asymptomatic patients were higher when compared with symptomatic patients. Further, the viral load had a negative trend with increasing age, while a significant decrease in viral loads was seen with increasing disease severity.
>a significant decrease in viral load was observed with increasing disease severity,” the researchers wrote in the paper.
>The team noted that factors tied to a poor prognosis, including bilateral ground-glass opacity in chest X-ray, low lymphocyte count, and older age, are correlated with low SARS-CoV-2 viral load.
>“COVID-19 is a complicated puzzle with pieces of many colors and shapes. Further, virologic and immunological studies are urgently needed to put all the pieces together and see the big picture,” the researchers added.
https://archive.vn/nAgPQ
Patients with severe SARS-2 found to be infectious up to 32 days
https://archive.vn/QRfRs
[]
SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis
>(?) No study detected live virus beyond day 9 of illness
https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(20)30172-5/fulltext
[Parkinsonism? (ParkinSARS) section]
SARS-CoV-2 and the risk of Parkinson's disease: facts and fantasy
>So far, 3 cases of parkinsonism have been reported after SARS-CoV-2 infection.
>two men aged 45 and 58 years, and a woman aged 35 years
>None of the male patients had a monogenic cause or known genetic predisposition for Parkinson's disease, while genetic tests were not done for the female patient. Onset was acute in the three cases (~20 days after SARS-2 diagnosis)
>Functional nigrostriatal neuroimaging was abnormal in all three cases, which implies dopaminergic nigrostriatal impairment, but is not diagnostic of Parkinson's disease
https://archive.vn/9eM8a
[Supplements this]
Parkinsonism as a Third Wave of the SARS-CoV-2 Pandemic?
>There may be a myriad of potential long-term neurological and neuropsychiatric complications secondary to SARS-CoV-2 infection including a potential link to worsening parkinsonism in patients with PD and possibly even delayed neurological effects including parkinsonism. It remains to be seen whether COVID-19 viral infections will be later linked to parkinsonism as is the case in other viruses.There are emerging tools available to identify parkinsonism early in the disease process
https://archive.vn/msyqb
>Extra 10,000 dementia deaths in England and Wales in April
http://archive.is/vMC5e
>Coronavirus Pandemic Led to Surge in Alzheimer’s Deaths
http://archive.is/2ZCTD
>Cerebral Micro-Structural Changes in SARS2 Patients – An MRI-based 3-month Follow-up Study
http://archive.is/5TtRR
>Determining the relationship between SARS-CoV-2 infection, dopamine, and SARS-2 complications
https://archive.vn/fNKjT
The possible immunoregulatory and anti-inflammatory effects of selective serotonin reuptake inhibitors in coronavirus disease patients
https://www.sciencedirect.com/science/article/pii/S0306987720322489
Functions of serotonin in hypoxic pulmonary vascular remodeling.
https://hal.archives-ouvertes.fr/hal-01274919/document
Hypoxia-induced secretion of serotonin from intact pulmonary neuroepithelial bodies in neonatal rabbit
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2290169/
Post-COVID Parkinsonism
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273038/pdf/MDS-9999-na.pdf
[Parkinsonism? section]
Scientists discover how SARS-2 virus causes multiple organ failure in mice
>Within seven days post-infection, all of the mice with COVID-19 had stopped eating and were completely inactive, and had lost, on average, about 20% of their body weight. Animals that had been engineered to carry the human ACE2 protein but had not been infected with the virus, on the other hand, did not lose a significant amount of weight.
>Moreover, the COVID-19 infected animals had altered levels of immune cells, swelling of the heart tissue and wasting away of the spleen — all symptoms that have been observed in people who are critically ill with COVID-19.
>Deb’s team also looked at which genes were turned on and off in the mice infected with SARS-CoV-2, and they discovered other signs of disease. Common molecular processes that help cells generate energy — through mechanisms known as the tricarboxylic acid cycle, or TCA cycle, and electron transport chain — were shut off in the heart, kidney, spleen and lungs.
>Finally, the study also revealed that some changes were long-lasting throughout the organs in mice with COVID-19. In addition to temporarily altering which genes were turned on and off in some cells, the virus made epigenetic changes, that could explain why, in some people with COVID-19, symptoms persist for weeks or months after their bodies are rid of the virus.
https://archive.vn/bGCkV
SARS-CoV-2 Infection Presenting with Hyperglycemia and Ketosis: A Case Series of Three Diabetic Patients
>excessive hyperglycemia and ketosis may manifest in diabetic patients with COVID-19 and the emergency and intensive care physicians should measure blood sugar and ketone levels on presentation in all diabetic patients and be careful about fluid management
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751029
[]
New-Onset Diabetes in SARS-2: Time to Frame Its Fearful Symmetry
>There is increasing evidence that coronavirus disease 2019 (COVID-19) may lead to new-onset diabetes mellitus (DM). This may occur even in patients without predisposing factors for impaired glucose metabolism. Both impaired pancreatic insulin secretion and insulin resistance have been implicated as underlying mechanisms. Importantly, new-onset hyperglycaemia is associated with worse prognosis in patients with COVID-19
>prognosis may be even more sinister than in patients with pre-existing DM
https://archive.vn/0jEjV
[]
New onset diabetes, type 1 diabetes and SARS-2
https://archive.vn/ml1l7
[]
An Immediate and Long-Term Complication of SARS-2 May Be Type 2 Diabetes Mellitus
https://archive.vn/ISwwE
Short of Breath for the Long Haul: Diaphragm Muscle Dysfunction in Survivors of Severe SARS-2 as Determined by Neuromuscular Ultrasound
>25 patients study from Chicago
>Many survivors from acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 (COVID-19) suffer from persistent dyspnea and fatigue long after resolution of the active infection. In a cohort of 25 consecutive COVID-19 ARDS survivors admitted to an inpatient rehabilitation hospital (76% male),
>80% of them had at least one sonographic abnormality of diaphragm muscle structure or function.
>Specifically, when compared to established normative data,
>76% had impaired contractility (reduced thickening ratio), and
>20% patients had atrophy (reduced muscle thickness).
>These findings support neuromuscular respiratory dysfunction as a highly prevalent underlying cause for prolonged functional impairments after hospitalization for COVID-19.
>Currently, long term dysfunction in these patients is primarily attributed to lung parenchymal damage, overlooking diaphragm dysfunction as a possible contributor.
>Given that the diaphragm is the main respiratory muscle, we speculate that prolonged dysfunction may be a factor in at least a subset of patients.
https://www.medrxiv.org/content/10.1101/2020.12.10.20244509v1
The D614G Mutation Enhances the Lysosomal Trafficking of SARS-CoV-2 Spike
>spike is trafficked to lysosomes and that the D614G mutation enhances the lysosomal sorting of spike and the lysosomal accumulation of spike-positive punctae in SARS-CoV-2-infected cells.
>Spike trafficking to lysosomes is an endocytosis-independent, vacuolar ATPase-dependent process, and spike-containing lysosomes drive lysosome clustering but display poor lysotracker labeling and reduced uptake of endocytosed materials.
>These results are consistent with the lysosomal pathway of coronavirus biogenesis and raise the possibility that a common mechanism may underly the D614G mutation's effects on spike protein trafficking in infected cells and the accelerated entry of SARS-CoV-2 into uninfected cells
>SARS-CoV-2 spike is trafficked to lysosomes
>lysosomes of spike-expressing cells accumulated in large clusters, a phenotype that was relatively uncommon in non-expressing cells
>This appearance is likely due to lysosome clustering rather than lysosome fusion: cells treated with vacuolin-1 contained swollen lysosomes several micrometers in diameter
>sizes and numbers of these lysosomes appeared to be similar in expressing and non-expressing cells, indicating that spike expression induces lysosome clustering rather than lysosome fusion
>Spike expression disrupts lysosome function
>Spike trafficking to lysosomes is resistant to inhibitors of endocytosis, microtubules, and secretion but sensitive to V-ATPase inhibition
https://www.biorxiv.org/content/10.1101/2020.12.08.417022v1
[reminder (read the contents of the link, preferably]
SARS-CoV-2 utilizes lysosomes to exit cells
https://archive.vn/03Y0A
Long-term SARS-CoV-2 RNA shedding and its temporal association to IgG seropositivity
>Thefinding that the time to IgG seropositivity can be shorter than the lower bound ofpositive PCR tests in some patients, suggests that SARS-CoV-2-positive patients can continue to shed viral RNA for days or even weeks while generating IgG antibodies.
https://journals.scholarsportal.info/pdf/20587716/v6inone/nfp_lsrsaitatis.xml
Scientists have linked the most severe form of SARS2 with five genes that affect lung inflammation and the body’s ability to fight off viruses.
>Their findings, from a study of 2,700 Covid-19 patients in intensive care units across Britain, point to several existing drugs that could be repurposed to treat people who risk becoming critically ill.
>The genes – called IFNAR2, TYK2, OAS1, DPP9 and CCR2 – partially explain why some people become desperately sick with Covid-19, while others are not affected, said Kenneth Baillie of Edinburgh University, co-author of the study published on Friday in Nature.
>The new information should help scientists design clinical trials of medicines that target specific antiviral and anti-inflammatory pathways.
>Among those with the most potential, Baillie said, should be a class of anti-inflammatory drugs called JAK inhibitors, including Eli Lilly’s arthritis drug baricitinib, which has been found to help hospitalised pneumonia patients in combination with Gilead’s remdesivir.
https://archive.is/SXzIK
Marine mammals’ adaptations to low oxygen offer new perspective on SARS-CoV-2
https://archive.vn/AeFNG
SARS-CoV-2 RNA (supposedly and presumably, actually not proven (yet)) reverse-transcribed and integrated into the human genome
https://www.biorxiv.org/content/10.1101/2020.12.12.422516v1
https://www.biorxiv.org/content/10.1101/2020.12.12.422516v1.full.pdf
[]
>tl;dr inconclusive until further research
>chimeric RNA sequences could've just happened from errors during template switching that would make the replication complex (https://archive.vn/lauTd) to jump from SARS-CoV-2 to human mRNA
>authors didn't present cell genomic DNA sequence spanning integration junctions with target site duplications and a poly-A tail, so those results could be as well artifacts
https://twitter.com/mw_fr/status/1338275889268760576
[]
The Correlation Between Clinical Features and Viral RNA Shedding in Outpatients With SARS-CoV-2
>patients with severe disease symptoms had significantly higher virus shedding over a long period of time after symptom onset than those with mild symptoms
>No correlation was found between the viral RNA shedding at the first visit and symptoms, such as fever, cough, shortness of breath, fatigue, anorexia, and muscular soreness, except sore throat
https://archive.vn/nnYNw
Time-lapse video was taken on the Etaluma LS620 by Tabb Sullivan and his group at Integral Molecular. HEK-293T cells expressing SARS-CoV-2 spike cells fusing to HEK-293T cells stably expressing hsACE2 forming giant syncytia
https://twitter.com/DNA_RNA_Uni/status/1338197228381483009
[]
Syncytia formation by SARS‐CoV‐2‐infected cells
https://www.embopress.org/doi/full/10.15252/embj.2020106267
[]
>SARS-CoV-2 infected cells express the viral Spike protein (S) at their surface and fuse with ACE2-positive neighbouring cells. Expression of S without any other viral proteins triggers syncytia formation
https://www.biorxiv.org/content/10.1101/2020.07.14.202028v1
Within-host genomics of SARS-CoV-2
>SARS-CoV-2 infections are characterised by low levels of within-host diversity across the entire viral genome, with evidence of strong evolutionary constraint in Spike, a key target of vaccines and antibody-based therapies
>potential vaccine-escape mutations are likely to be rare in infectious individuals. Nonetheless, we identified Spike variants present in multiple individuals that may affect receptor binding or neutralisation by antibodies. Since the fitness advantage of escape mutations in highly-vaccinated populations is likely to be substantial, resulting in rapid spread if and when they do emerge, these findings underline the need for continuedvigilance and monitoring
https://www.biorxiv.org/content/10.1101/2020.05.28.118992v4
https://www.biorxiv.org/content/10.1101/2020.05.28.118992v4.full.pdf
The Potential for SARS-CoV-2 to Evade Both Natural and Vaccine-induced Immunity
https://www.biorxiv.org/content/10.1101/2020.12.13.422567v1
Vascular Alterations Among Young Adults With SARS-2
https://archive.vn/cV5ss
Elevated Biomarker for Blood Vessel Damage Found in All Children With SARS-2
https://archive.vn/Olp3N
Neutralising antibodies drive Spike mediated SARS-CoV-2 evasion
https://www.medrxiv.org/content/10.1101/2020.12.05.20241927v1
Evidence of exposure to SARS-CoV-2 in cats and dogs from households in Italy
>we report a large-scale study to assess SARS-CoV-2 infection in 919 companion animals living in northern Italy, sampled at a time of frequent human infection. No animals tested PCR positive. However, 3.3% of dogs and 5.8% of cats had measurable SARS-CoV-2 neutralizing antibody titers, with dogs from COVID-19 positive households being significantly more likely to test positive than those from COVID-19 negative households
https://archive.vn/aYx8Z
[Autoantibodies section]
High frequency of cerebrospinal fluid autoantibodies in SARS-2 patients with neurological symptoms
>Most patients showed signs of CSF inflammation and increased levels of neurofilament light chain
>All patients had anti-neuronal autoantibodies in serum or CSF when assessing a large panel of autoantibodies against intracellular and surface antigens relevant for central nervous system diseases using cell-based assays and indirect immunofluorescence on murine brain sections
>Antigens included proteins well-established in clinical routine, such as Yo or NMDA receptor, but also a variety of specific undetermined epitopes on brain sections, including vessel endothelium, astrocytic proteins and neuropil of basal ganglia, hippocampus or olfactory bulb.
>high frequency of autoantibodies targeting the brain in the absence of other explanations suggests a causal relationship to clinical symptoms (myoclonus, seizures)
http://archive.is/bxxGY
Diverse Functional Autoantibodies in Patients with SARS-2
https://www.medrxiv.org/content/10.1101/2020.12.10.20247205v2
Blood samples from 987 gravely ill SARS-2 patients from around the world - in 10.2%, antibodies that attacked and neutralized the patients’ own type I interferon were identified. A subgroup of affected had extremely low blood levels of this interferon
>Antibodies knocked the interferon out of action and cells exposed to the patients’ plasma failed to fend off virus invasion
>No 663 people in a control group with mild or asymptomatic SARS-CoV-2 infection had those damaging antibodies. Also they were scarce in the general population, showing up in only 0.33%
https://archive.vn/TOjUY
SARS-2 Linked to Development of Myasthenia Gravis
>MG is a rare autoimmune disorder caused by an antibody-mediated blockade of neuromuscular transmission resulting in skeletal muscle weakness. The autoimmune attack occurs when autoantibodies form against the nicotinic acetylcholine postsynaptic receptors at the neuromuscular junction of skeletal muscles
http://archive.is/Ok3cP
[Autoantibodies section]
Acute appendicitis may be associated with SARS-2 in children
>Researchers encourage SARS-CoV-2 testing of children with severe gastrointestinal symptoms
>Firstly, gastrointestinal symptoms occur frequently in children with COVID-19, and gastrointestinal involvement is increasingly becoming recognized among SARS-CoV-2-infected children.
>Secondly, a persistent viral infection of the gastrointestinal tract has been observed in cases of COVID-19. For example, one study conducted earlier this year (2020) found that one-fifth of SARS-CoV-2-infected patients had detectable viral RNA in their fecal samples, even following negative conversion of viral RNA in the respiratory tract.
>In addition, researchers studying an animal model of SARS-CoV-2 infection detected a higher level of viral RNA in the gastrointestinal tract than in the respiratory tract.
>The evidence to date also suggests that SARS-CoV-2 can be secreted by infected intestinal cells.
>Third, the host cell receptor for SARS-CoV-2, called angiotensin-converting enzyme 2 (ACE2), is expressed at high levels in the intestinal lining.
>Furthermore, “as ACE2 is present on glandular cells in the appendix, the appendix is also a viral target of SARS-CoV-2,” writes the team.
>Researchers have described four cases of children presenting with acute appendicitis who were also found to be infected with SARS-CoV-2, suggesting a potential association.
>In all four cases, computed tomography of the pelvis revealed a dilated and fluid-filled appendix and fat stranding consistent with edema and acute inflammation. Polymerase-chain-reaction (PCR) testing of nasopharyngeal swab samples revealed that all patients were infected with SARS-CoV-2
https://archive.vn/UGIg4
Are commercial antibody assays substantially underestimating SARS-CoV-2 infection? An analysis on a population-based sample in a high exposure setting
>All three assays had comparable performance and excellent agreement, but missed at least 20% of individuals with past or current infection. Commercial antibody assays can substantially underestimate ever infection, more so when infection rates are high
https://www.medrxiv.org/content/10.1101/2020.12.14.20248163v1
Surface proteins of SARS-CoV-2 drive airway epithelial cells to induce interferon-dependent inflammation
>we demonstrate both in vitro and in vivo that the SARS-CoV-2 surface proteins Spike (S) and Envelope (E) activate the key immune signaling interferon (IFN) pathway in both immune and epithelial cells (!)independent of viral infection and replication(!)
>These proteins induce reactive oxidative species generation and increases in human and murine specific IFN-responsive cytokines and chemokines, similar to their upregulation in critically ill COVID-19 patients
>Induction of IFN signaling is dependent on canonical but discrepant inflammatory signaling mediators as the activation induced by S is dependent on IRF3, TBK1, and MYD88 while that of E is largely MYD88 independent
>these viral surface proteins, specifically E, induced peribronchial inflammation and pulmonary vasculitis in a mouse model. Finally we show that the organized inflammatory infiltrates are dependent on type I IFN signaling, specifically in lung epithelial cells
https://www.biorxiv.org/content/10.1101/2020.12.14.422710v1
Rapid detection of SARS-CoV-2 with Cas13
https://www.medrxiv.org/content/10.1101/2020.12.14.20247874v1
Possible vertical transmission and antibodies against SARS-CoV-2 among infants born to mothers with SARS-2: A living systematic review
>About 517 studies were pooled, where 33 articles (5.8%) met the inclusion criteria such as infection prevention and control measures at birth. A total of 205 infants born to COVID-19 positive mothers were studied. Overall, 6.3% (13/205; 95% CI: 3.0%-9.7%) of the infants tested positive for COVID-19 virus at birth
>current evidence revealed a low possibility of vertical transmission of COVID-19 and antibodies against SARS-CoV-2 were detected among vertically exposed but negative infants
https://archive.vn/tEqqF
SARS-CoV-2 spike protein can flex to find a receptor
>3D structures of the spike imaged in different orientations on the virus surface using cryo-electron tomography
https://twitter.com/BriggsGroup/status/1339524431098617856
International call for cases identified 38 children with neurological disease related to SARS-CoV-2
>postinfectious immune-mediated acute disseminated encephalomyelitis-like changes of the brain (16 patients)
>myelitis (eight patients)
>Splenial lesions (seven patients )and myositis (four patients) were predominantly observed in children with multisystem inflammatory syndrome
>and neural enhancement (13 patients). Cranial nerve enhancement could occur in the absence of corresponding neurological symptoms.
https://archive.vn/OQ95J
Assessing the Safety of Home Oximetry for SARS-2: A multi-site retrospective observational study.
>This study find that home oximetry monitoring can be a safe pathway for Covid-19 patients; and indicates increases in risk to vulnerable groups and patients with oxygen saturations < 95% at enrolment, and in those enrolled on discharge from hospital. Findings from this evaluation have contributed to the national implementation of home oximetry across England, and further work will be undertaken to evaluate clinical effectiveness of the new pathway.
https://www.medrxiv.org/content/10.1101/2020.12.16.20248302v1
Detection of long SARS-CoV-2 nucleocapsid sequences in peripheral blood monocytes collected soon after hospital admission
https://www.biorxiv.org/content/10.1101/2020.12.16.423113v1
Possible Aerosol Transmission of SARS-CoV-2 Associated with an Outbreak in an Apartment in Seoul, South Korea, 2020
>Scientists have strongly implied the aerosol transmission of COVID-19.
>An outbreak occurred along two vertical lines in an apartment in South Korea.
>The virus can be spread through the air duct by the (reverse) stack effect.
>Aerosol transmission indoors with insufficient ventilation need to be appreciated.
https://www.sciencedirect.com/science/article/pii/S1201971220325583
Incubation period of SARS-2: A systematic review and meta-analysis
>The mean incubation period ranged from 5.6 (95% CI: 5.2–6.0) to 6.7 days
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698828
Median presymptomatic infectious period across studies varied over <1–4 days
https://archive.vn/mz7tK
Physiological Effects of Exercising at Different Intensities Wearing TNT or Double-layer Cotton Facemasks Compared to Not Wearing a Mask
>No adverse changes to human health were observed
https://www.medrxiv.org/content/10.1101/2020.12.11.20203224v1
[reminder] SARS-2 is a seasonal climate-driven disease across both hemispheres
>The role of climate in the population dynamics of COVID-19 remains poorly understood, and a true seasonal signature has remained elusive. Data from both hemispheres and the second wave provide opportunities to further examine climatic drivers. With a statistical method designed to detect transitory associations, we show consistent negative effects of temperature and absolute humidity at large spatial scales. At finer spatial resolutions we substantiate these connections during the seasonal rise and fall of COVID-19.
>Strong disease responses are identified between 12-18degC for Temperature and 4-12 g/m3 for Absolute Humidity.
>These results classify COVID-19 as a seasonal low temperature infection, and point to the airborne pathway as an important contribution to transmission for SARS-CoV-2, with implications for control measures we discuss.
https://www.medrxiv.org/content/10.1101/2020.12.16.20248310v1
Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection
https://www.jci.org/articles/view/140491/pdf
[chink study with chink datasets, careful] Cell-cell interactions are significantly different in SARS-2 patients
>in healthy controls, most cell-cell interactions are between basal, ciliated, and goblet cells of the lung epithelium, with dendritic cells providing immune surveillance. As disease severity increases, cell-cell interactions become dominated by interactions between the lung epithelium and proinflammatory players within the immune compartment.
>in monocyte-related interactions, COVID-19 patients generally have more cell-cell interactions than healthy controls
>Reduced T cell interactions and increased monocyte interactions in severe COVID-19 patients across different compartments
>higher interactions between monocyte/macrophage or T cells towards neutrophils in severe patients
>severe patients have a decrease in CD8 memory T cell interactions. The lack of T cell interactions in severe patients suggests potential T cell depletion,
>Monocyte/macrophage and neutrophil interaction in severe patients are dominated by IL1B, IL1RN, IL8, TNFRSF1B, CCL4, IFIT2, IFIT3, CCL8, CXCL10, CXCL11, CCL2, CXCL1, CXCL2 and CXCL5 and other inflammation pathways
>Interaction from goblet cells to immune cells are heterogeneous in moderate patients and severe patients
>Cell-cell interaction patterns have the potential to discriminate between moderate and severe patients
https://www.biorxiv.org/content/10.1101/2020.12.30.424641v1.full.pdf
[Read the full, can't fit it all in high-lights] Meta-analysis of virus-induced host gene expression reveals unique signatures of immune dysregulation induced by SARS-CoV-2
https://www.biorxiv.org/content/10.1101/2020.12.29.424739v1
SARS-CoV-2 spike glycoprotein S1 induces neuroinflammation in BV-2 microglia
(Microglial cells are the resident macrophages of the central nervous system)
>we investigated the effects of the SARS‐CoV‐2 spike glycoprotein S1 stimulation on neuroinflammation in BV-2 microglia
>Analyses of culture supernatants revealed an increase in the production of TNFα, IL-6, IL-1β and iNOS/NO. SARS‐CoV‐2 spike glycoprotein S1 increased protein expressions of phospho-p65 and phospho-IκB, as well as enhancing DNA binding and transcriptional activity of NF-κB.
>Pro-inflammatory effects of the glycoprotein effects were reduced in the presence of BAY11-7082 (1 μM).
>The presence of SARS‐CoV‐2 spike glycoprotein S1 in BV-2 microglia increased the protein expression of NLRP3, as well as caspase-1 activity. However, pre-treatment with CRID3 (1 μM) or BAY11-7082 (1 μM) resulted in the inhibition of NLRP3 inflammasome/caspase-1.
>It was also observed that CRID3 attenuated SARS‐CoV‐2 spike glycoprotein S1-induced increase in IL-1β production. Increased protein expression of p38 MAPK was observed in BV-2 microglia stimulated with the spike glycoprotein S1, and was reduced in the presence of SKF 86002.
>results have provided the first evidence demonstrating SARS-CoV-2 spike S1 glycoprotein-induced neuroinflammation in BV-2 microglia
>promotion of neuroinflammation by this glycoprotein is mediated through activation of NF-κB, NLRP3 inflammasome and p38 MAPK. These results are significant because of their relevance to our understanding of neurological and neuropsychiatric symptoms observed in patients infected with SARS-CoV-2.
https://www.biorxiv.org/content/10.1101/2020.12.29.424619v1
Microvascular Injury in the Brains of Patients with SARS-2
https://archive.vn/LVg6F
[ADE? section]
An infectivity-enhancing site on the SARS-CoV-2 spike protein is targeted by SARS-2 patient antibodies
>we screened a series of anti-spike monoclonal antibodies from COVID-19 patients, and found that some of antibodies against the N-terminal domain (NTD) dramatically enhanced the binding capacity of the spike protein to ACE2, and thus increased SARS-CoV2 infectivity. Surprisingly, mutational analysis revealed that all the infectivity-enhancing antibodies recognized a specific site on the surface of the NTD. The antibodies against this infectivity-enhancing site were detected in all samples of hospitalized COVID-19 patients in the study. However, the ratio of infectivity-enhancing antibodies to neutralizing antibodies differed among patients. Furthermore, the antibodies against the infectivity-enhancing site were detected in 3 out of 48 uninfected donors, albeit at low levels. These findings suggest that the production of antibodies against SARS-CoV-2 infectivity-enhancing site could be considered as a possible exacerbating factors for COVID-19 and that a spike protein lacking such antibody epitopes may be required for safe vaccine development, especially for individuals with pre-existing enhancing antibodies
https://www.biorxiv.org/content/10.1101/2020.12.18.423358v1
The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates
>A safety concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated potent NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike protein from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV-1 infection
>Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of antibody binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement
>However, both in vitro neutralizing and infection-enhancing RBD or infection-enhancing NTD antibodies protected from SARS-CoV-2 challenge in non-human primates and mice. One of 30 monkeys infused with enhancing antibodies had lung pathology and bronchoalveolar lavage cytokine evidence suggestive of enhanced disease
https://www.biorxiv.org/content/10.1101/2020.12.31.424729v1
https://www.biorxiv.org/content/10.1101/2020.12.31.424729v1.full.pdf
Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies
https://archive.vn/vvfrv
>Evidence of ADE in coronavirus infections in vitro
>Findings to date argue against macrophages as productive hosts of SARS-CoV-2 infection
Some of the findings on this:
>“our data show that the presence of an intrauterine bacterial infection results in the infiltration of ACE2 expressing maternal macrophage and neutrophils into and across the placental tissues.These ACE2 expressing immune cells have the potential to transport the virus to the placenta in cases of COVID-19 infection in pregnancy and increase the risk of placental infection and vertical transmission of the virus to the fetus.
https://archive.vn/rODrd
Monocytes and macrophages, targets of SARS-CoV-2: the clue for SARS-2 immunoparalysis
>Although monocytes and macrophages express the molecular machinery to recognize and internalize SARS-CoV-2 such as ACE2, TMPRSS2 and ADAM17 (24), the ability of the virus to replicate within these cells is not fully understood. Our results favor the hypothesis of an abortive infection similar to SARS-CoV-1 (28) but clearly distinct from MERS-CoV replication in macrophages (29)
https://www.biorxiv.org/content/10.1101/2020.09.17.300996v1
>monocytes and macrophages can either be infected by, or phagocytize, SARS-CoV-2
https://www.biorxiv.org/content/10.1101/2020.07.17.209304v1.full.pdf
[ADE? section]
Impact of SARS-CoV-2 Infection on the Epidemiology of Chronic Pain and Long-Term Disability: Prepare for the Next Perfect Storm
[...]
[lots of content in that article, a nice recap on long-term problems, too]
[...]
>The challenge of reintegrating survivors of COVID-19 into the workplace will be vital for the recovery of the economy. These patients will however not only require prolonged rehabilitation but are also in need of integrated multidisciplinary anti-nociceptive therapeutic approaches. Some of the symptoms presented by such survivors should be considered as psychological traumatic effects of the acute infectious illness.
>Countries should therefore monitor survivors of COVID-19 to identify risk factors for the development of post-traumatic stress syndrome (PTSD) and chronic pain and primary pain (widespread pain) syndromes. PTSD is commonly comorbid with chronic pain conditions. Patients with pain and PTSD as a comorbidity report significantly greater pain severity and have a higher number of complaints of pain.
>This may be attributable to the hyperalgesic state often observed in PTSD patients, which may in turn be related to central sensitization. Furthermore, 39.7% of patients with neuropathic pain conditions have PTSD, which is much higher than the prevalence of PTSD in the general population with chronic pain (9.8%)
https://archive.vn/uLJyB
Cutaneous Manifestations of SARS-2: A Case Series from Brazil
>Twenty five cases of COVID-19 with cutaneous manifestations (urticaria, erythematous rash, maculopapular eruption, pruritus, erythema multiforme-like lesions, dyshidrotic eczema) were observed during, after and before systemic symp-toms. A few cases with skin involvement were also observed as isolated symptoms of the viral infection. These data demonstrate the clinical polymorphism related to skin involvement of patients infected with SARS-CoV-2
https://revista.spdv.com.pt/index.php/spdv/article/view/1281/866
Coinfection with Respiratory Pathogens in SARS-2 in Korea
>From the study subjects (N = 258) retrospectively enrolled when confirmed as SARS-CoV-2 positive, nasopharyngeal (NPS), oropharyngeal swabs (OPS), and sputum specimens were restored for retesting SARS-CoV-2 and detecting respiratory pathogens. Majority of the study subjects (95.7%, N = 247) were confirmed as SARS-CoV-2 positive using NPS/OPS specimens, suggesting that the upper respiratory specimen is most valuable in detecting SARS-CoV-2. Coinfection rates in COVID-19 patients (N = 258) with respiratory pathogens were 9.7% (N = 25); 8.5% (N = 22) respiratory viruses and 1.2% (N = 3) Mycoplasma pneumoniae, an atypical bacterium. Of the respiratory virus coinfection cases (N = 22), 20 (90.9%) were co-infected with a single respiratory virus and 2 (0.8%) (metapneumovirus/adenovirus and rhinovirus/bocavirus 1/2/3/4) with two viruses. Respiratory viruses in single viral coinfection cases with SARS-CoV-2 were as follows: non-SARS-CoV-2 coronaviruses (229E, NL63, and OC43, N = 5, 1.9%), rhinovirus (N = 4, 1.6%), metapneumovirus (N = 3, 1.2%), influenza A (N = 3, 1.2%), respiratory syncytial virus A and B (N = 3, 1.2%), and adenovirus (N = 2, 0.8%). No mixed coinfections with respiratory viruses and M. pneumoniae were found. In conclusion, the diagnostic value of utilizing NPS/OPS specimen is excellent, and, as the first report in Korea, coinfection with respiratory pathogens were detected at a rate of 9.7% in patients with COVID-19
https://www.medrxiv.org/content/10.1101/2020.12.18.20248449v1
[Netherlands] Risk of thrombotic complications in influenza versus SARS-2 hospitalized patients (general ward and ICU combined)
>Of the 13.217 hospitalized influenza patients, 437 (3.3%) were diagnosed with thrombotic complications, versus 66 (11%) of the 579 hospitalized COVID19 patients. The 30 day cumulative incidence of any thrombotic complication in influenza was 11% (95%CI 9.4-12) versus 25% (95%CI 18-32) in COVID19. For venous thrombotic complications (VTE) and arterial thrombotic complications alone, these numbers were respectively 3.6% (95%CI 2.7-4.6) and 7.5% (95%CI 6.3-8.8) in influenza versus 23% (95%CI 16-29) and 4.4% (95%CI 1.9-8.8) in COVID19. Conclusions: The incidence of thrombotic complications in hospitalized influenza patients was lower than in hospitalized COVID19 patients in our study.
>This difference was mainly driven by a high risk of VTE complications in the COVID19 patients admitted to ICU
https://www.medrxiv.org/content/10.1101/2020.12.18.20248265v1
SARS-CoV-2 protein ORF3a is pathogenic in Drosophila and causes phenotypes associated with SARS-2 post-viral syndrome
https://www.biorxiv.org/content/10.1101/2020.12.20.423533v1
SARS-2 Myocardial Pathology Evaluation in AthleTEs with Cardiac Magnetic Resonance (COMPETE CMR)
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.052573
In vitro characterization of engineered red blood cells as potent viral traps against HIV-1 and SARS-CoV-2
>Engineered red blood cells (RBCs) expressing viral receptors could be used therapeutically as viral traps as RBCs lack nuclei and other organelles required for viral replication. Here we show that the combination of a powerful erythroid-specific expression system and transgene codon optimization yields high expression levels of the HIV-1 receptors CD4 and CCR5, as well as a CD4-glycophorin A (CD4-GpA) fusion protein on enucleated RBCs. Engineered RBCs expressing CD4 and CCR5 were efficiently infected by HIV-1, but CD4 or CD4-GpA expression in the absence of CCR5 was sufficient to potently neutralize HIV-1 in vitro. To facilitate continuous large-scale production of engineered RBCs, we generated erythroblast cell lines stably expressing CD4-GpA or ACE2-GpA fusion proteins, which produced potent RBC viral traps against HIV-1 and SARS-CoV-2. Our results suggest that this approach warrants further investigation as a potential treatment against viral infections
https://www.biorxiv.org/content/10.1101/2020.12.20.423607v1
https://www.biorxiv.org/content/10.1101/2020.12.20.423607v1.full.pdf
SARS-2 patients plagued by symptoms months after infection
>High rate of persistent symptoms up to 4 months after community and hospital-managed SARS-CoV-2 infection
>N=78. The mean patient age is 47. The most common reported initial COVID-19 symptoms were fatigue in 62, cough in 50, and headache in 44 individuals. At median 69 days after diagnosis, 31 patients had persistent symptoms including fatigue in 17, shortness of breath in 15 and chest tightness in 4, including 7 hospitalised and 24 community-managed individuals. Complex lung function testing at median 113 days post-infection was performed in 65 individuals. Abnormal total lung capacity (TLC) < lower limit of normal (LLN) was seen in a small proportion of patients (12%), but median TLC %-predicted was significantly lower in the hospitalised 91 compared with the community population 102. Abnormal diffusion capacity for carbon monoxide %-predicted, less than LLN values, was observed in 11 individuals with a trend to higher proportions in the hospitalised population. This may indicate an association with pulmonary vascular disease. Neurocognitive impairment, performed under supervision by trained examiners using the CogState computerised battery, was low but associated with abnormal olfaction. Concerningly, a considerable proportion of patients experience persistent symptoms after SARS-CoV-2 infection including fatigue, chest pain and breathlessness. 35% community-managed patients within ADAPT have persistent symptoms several months post infection
https://archive.vn/o1dsa
Identification of NPC1 as a novel SARS-CoV-2 intracellular target
>Niemann-Pick type C1 (NPC1) receptor is an endosomal membrane protein that regulates intracellular cholesterol trafficking, which is crucial in the Ebola virus (EBOV) cycle. The severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) enters the cell by binding of the viral spike (S) protein to the ACE2 receptor. This requires S-protein processing either by the surface transmembrane serine protease TMPRSS2 for plasma membrane fusion or cathepsin L for endosomal entry. Additional host factors are required for viral fusion at endosomes. Here, we report a novel interaction of the SARS-CoV-2 nucleoprotein (N) with the cholesterol transporter NPC1. Moreover, small molecules interfering with NPC1 that inhibit EBOV entry, also inhibited human coronavirus. Our findings suggest an important role for NPC1 in SARS-CoV-2 infection, a common strategy shared with EBOV, and a potential therapeutic target to fight against COVID-19
https://www.biorxiv.org/content/10.1101/2020.12.19.423584v1
Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 without end-organ failure.
https://www.nejm.org/doi/full/10.1056/NEJMoa2033130
The SARS-CoV-2 spike protein disrupts the cooperative function of human cardiac pericytes - endothelial cells through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease
>We investigated the effects of the recombinant, stabilised S protein on primary human cardiac pericytes (PCs) signalling and function. Endpoints included cell viability, proliferation, migration, cooperation with endothelial cells (ECs) in angiogenesis assays, and release of pro-inflammatory cytokines.
>Adopting a blocking strategy against the S protein receptors ACE2 and CD147, we explored which receptor mediates the S protein signalling in PCs.
>We show, for the first time, that the recombinant S protein alone elicits functional alterations in cardiac PCs.
>This was documented as:
>(1) increased migration,
>(2) reduced ability to support EC network formation on Matrigel,
>(3) secretion of pro-inflammatory molecules typically involved in the cytokine storm; and
>(4) production of pro-apoptotic factors responsible for EC death.
>Furthermore, the S protein stimulates the phosphorylation/activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) through the CD147 receptor, but not ACE2, in cardiac PCs. Accordingly, the neutralization of CD147, using a blocking antibody, prevented the activation of ERK1/2 and partially rescued the PC function in the presence of the S protein
https://www.biorxiv.org/content/10.1101/2020.12.21.423721v1
Host Cell Proteases Drive Early or Late SARS-CoV-2 Penetration
https://www.biorxiv.org/content/10.1101/2020.12.22.423906v1
SARS-CoV-2 Envelope (E) Protein Interacts with PDZ-Domain-2 of Host Tight Junction Protein ZO1
https://www.biorxiv.org/content/10.1101/2020.12.22.422708v1
[Neanderthal section]
A Neanderthal OAS1 isoform Protects Against SARS-2 Susceptibility and Severity: Results from Mendelian Randomization and Case-Control Studies
https://www.medrxiv.org/content/10.1101/2020.10.13.20212092v4
>SARS-2: Neanderthal DNA increases risk of serious disease
https://archive.vn/usJNU
>German researchers have now investigated the question of whether our Neanderthal heritage also plays a role in the current number one topic, the Covid-19 pandemic. And according to the Max Planck Institute for Evolutionary Anthropology in Leipzig (MPI EVA) it does - unfortunately not in a positive way: "It is terrifying that the genetic legacy of the Neanderthals is having such tragic effects during the current pandemic," comments Svante Pääbo , Director at MPI EVA, the latest findings.
Neanderthal DNA in Modern Human Genomes Is Not Silent
https://www.the-scientist.com/features/neanderthal-dna-in-modern-human-genomes-is-not-silent-66299
Africans carry surprising amount of Neanderthal DNA
https://archive.vn/5ds6y
>New study found similar amounts of Neanderthal DNA in Europeans and Asians—51 and 55 Mb, respectively
>Studies had suggested East Asians have 20% more Neanderthal DNA than Europeans, she notes.
>The researchers found that African individuals on average had 17 Mb worth, or 0.3% of their genome
>2-8% of people in Eurasia carry a variant promoter region of the Neandertal DPP4 variant that doubles the risk to become critically ill in SARS-2
https://www.biorxiv.org/content/10.1101/2020.12.11.422139v1
>Our docking study shows a strong affinity of nCOVID spike protein towards DPP4 receptor
https://www.biorxiv.org/content/10.1101/2020.09.06.285023v1.full
[Neanderthal section]
[niggers BTFO section]
>SARS-2 deaths detected in a systematic post-mortem surveillance study in Africa
>Contrary to expectations, CV19+ deaths were common in Lusaka. The majority occurred in the community where testing capacity is lacking. Yet few who died at facilities were tested, despite presenting with typical symptoms of CV19. Therefore, CV19 cases were under reported because testing was rarely done, not because CV19 was rare
>impact of CV19 in Africa has been vastly underestimated
https://www.medrxiv.org/content/10.1101/2020.12.22.20248327v1
>A government analysis showed that there had been more than twice as many excess deaths as could be explained by confirmed cases in South Africa
>With stricter control measures lifted and many people no longer seeing the virus as a threat, public health officials fear that Africa’s second wave could be far worse than its first
https://archive.vn/mhFY4
Vitamin D deficiency and insufficiency in Africa and the Middle East, despite year-round sunny days
>Despite significant daily sunlight availability in Africa and the Middle East, persons living in these regions are frequently vitamin D insufficient or deficient. Vitamin D insufficiency (25-hydroxyvitamin D (25(OH)D) between 15 and 20 ng/mL (37.5 - 50 nmol/L)) has been described in various population groups, ranging from 5% to 80%. Risk factors include traditional dress and avoidance of sunlight exposure, and multiple dietary factors as a result of specific cultural beliefs. Vitamin D resistance due to calcium deficiency mechanisms has been described in similar population groups, which may lead to hypovitaminosis D.
https://archive.vn/efwFm
African-centric TP53 variant increases iron accumulation and bacterial pathogenesis but improves response to malaria toxin
>A variant at amino acid 47 in human TP53 exists predominantly in individuals of African descent. P47S human and mouse cells show increased cancer risk due to defective ferroptosis. Here, we show that this ferroptotic defect causes iron accumulation in P47S macrophages. This high iron content alters macrophage cytokine profiles, leads to higher arginase level and activity, and decreased nitric oxide synthase activity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981190
[]
SARS-CoV-2: hemoglobin, iron, and hypoxia beyond inflammation
>Scientific literature has pointed out potential pathophysiological mechanisms:
[...]
>vii) ferroptosis with oxidative stress and lipoperoxidation;
http://archive.is/MowCB
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267810/pdf/cp-10-1-1271.pdf
[]
>ferroptosis triggered by SARS-2:
https://www.researchgate.net/publication/341055648_COVID-19_iron_ferroptosis_parafibrin
[]
>Case report: Fatal lymphocytic cardiac damage in SARS-2: autopsy reveals a ferroptosis signature
https://archive.vn/prYO1
[niggers BTFO section]
A Systematic Review of the Incubation Period of SARS-CoV-2: The Effects of Age, Biological Sex, and Location on Incubation Period
>people who experience more severe disease due to SARS-CoV-2 may have a shorter incubation period
https://www.medrxiv.org/content/10.1101/2020.12.23.20248790v1
Detection and molecular characterisation of SARS-CoV-2 in farmed mink (Neovision vision) in Poland
>there is a high risk that more Polish mink farms become a source for SARS-CoV-2
https://www.biorxiv.org/content/10.1101/2020.12.24.422670v1
Identification of SARS-2-relevant transcriptional regulatory networks and associated kinases as potential therapeutic targets
>results identified classical antiviral response pathways including Interferon response factors (IRFs), interferons (IFNs), and JAK-STAT signaling as key elements upregulated by SARS-CoV-2 in comparison to mock-treated cells. In addition, comparing SARS-Cov-2 infection of airway epithelial cells to other respiratory viruses identified pathways associated with regulation of inflammation (MAPK14) and immunity (BTK, MBX) that may contribute to exacerbate organ damage linked with complications of COVID-19
https://www.biorxiv.org/content/10.1101/2020.12.23.424177v1
Characterizing Long SARS-2 in an International Cohort: 7 Months of Symptoms and Their Impact
https://www.medrxiv.org/content/10.1101/2020.12.24.20248802v2
Long SARS-2 patients haunted by ‘unbearable’ smells of fish, sulphur, and burnt toast
>ENT (ear, nose and throat) surgeon Professor Nirmal Kumar said this “very strange and very unique” long-term symptom, known as parosmia, seems to be affecting young people and healthcare workers in particular.
>The surgeon, who is also the president of ENT UK, noticed that some patients with long-term anosmia were recovering, only to experience parosmia.
https://archive.vn/z41OW
ACE2 partially dictates the host range and tropism of SARS-CoV-2
https://archive.vn/dZaaD
Cross-neutralization of SARS-CoV-2 by HIV-1 specific broadly neutralizing antibodies and polyclonal plasma
>S protein of SARS-CoV-2, similar to type I fusion proteins of viruses such as HIV-1 envelope (Env) and influenza hemagglutinin, is heavily glycosylated.
>Viral Env glycans, though host derived, are distinctly processed and thereby recognized or accommodated during antibody responses.
>In recent years, highly potent and/or broadly neutralizing human monoclonal antibodies (bnAbs) that are generated in chronic HIV-1 infections have been defined.
>These bnAbs exhibit atypical features such as extensive somatic hypermutations, long complementary determining region (CDR) lengths, tyrosine sulfation and presence of insertions/deletions, enabling them to effectively neutralize diverse HIV-1 viruses despite extensive variations within the core epitopes they recognize.
>As some of the HIV-1 bnAbs have evolved to recognize the dense viral glycans and cross-reactive epitopes (CREs), we assessed if these bnAbs cross-react with SARS-CoV-2.
>Several HIV-1 bnAbs showed cross-reactivity with SARS-CoV-2 while one HIV-1 CD4 binding site bnAb, N6, neutralized SARS-CoV-2. Furthermore, neutralizing plasma antibodies of chronically HIV-1 infected children showed cross neutralizing activity against SARS-CoV-2
>human monoclonal antibodies tolerating extensive epitope variability can be leveraged to neutralize pathogens with related antigenic profile
https://www.biorxiv.org/content/10.1101/2020.12.09.418806v1
[SARS-CoV-2 and DPP4 receptor]
https://archive.4plebs.org/pol/thread/267206167/#267233074
>The MERS-CoV Receptor DPP4 as a Candidate Binding Target of the SARS-CoV-2 Spike
https://archive.vn/Qrw4l
If SARS-CoV-2 binds to DPP4 better than before (recombination with MERS-CoV possible if yes?), then people with Neanderthal genes, diabetics and/or renal tumor patients will become more susceptible
And people that got beetus from corona will get more susceptible to reinfection, too
An Immediate and Long-Term Complication of SARS-2 May Be Type 2 Diabetes Mellitus
https://archive.vn/ISwwE
>In type 2 diabetes mellitus, the activity of DPP4 seems to be increased
https://www.hindawi.com/journals/bmri/2015/816164/
The MERS-CoV receptor gene is among SARS-CoV-2 risk factors inherited from Neandertals
>In the current SARS-CoV-2 pandemic, two genetic regions derived from Neandertals have been shown to increase and decrease, respectively, the risk of falling severely ill upon infection. Here, we show that 2-8% of people in Eurasia carry a variant promoter region of the DPP4 gene inherited from Neandertals. This gene encodes an enzyme that serves as a receptor for the coronavirus MERS-CoV and is currently not believed to be a receptor for SARS-CoV-2. However, the Neandertal DPP4 variant doubles the risk to become critically ill in COVID-19.
>Barring other factors that may affect disease outcome, this means that, if alive today, a late Neandertal individual would have ~4-16 times higher risk of becoming critically ill if infected by SARS-CoV-2. This may support speculations that epidemic diseases could have played a role in the demise of Neandertals
https://www.biorxiv.org/content/10.1101/2020.12.11.422139v1
>renal tumor and normal tissues exhibited increased levels of ACE2, DPP4, ANPEP, and ENPEP
http://archive.is/b7Vsi
https://www.biorxiv.org/content/10.1101/2020.07.02.184663v1.full.pdf
>Using molecular docking, we study the affinity of the nCOVID-19 spike protein with cell receptors overexpressed under disease conditions. Our results suggest that certain cell receptors such as DC/L-SIGN, DPP4, IL22R and ephrin receptors could act as potential receptors for the spike protein. The receptor binding domain of nCOVID-19 is more flexible than that of SARS-COV and has a high propensity to undergo phase separation. Higher flexibility of nCOVID-19 receptor binding domain might enable it to bind multiple receptor partners
>Our docking study shows a strong affinity of nCOVID spike protein towards DPP4 receptor
https://www.biorxiv.org/content/10.1101/2020.09.06.285023v1.full
[SARS-CoV-2 and DPP4 receptor]
Cross-neutralization of SARS-CoV-2 by HIV-1 specific broadly neutralizing antibodies and polyclonal plasma
>S protein of SARS-CoV-2, similar to type I fusion proteins of viruses such as HIV-1 envelope (Env) and influenza hemagglutinin, is heavily glycosylated.
>Viral Env glycans, though host derived, are distinctly processed and thereby recognized or accommodated during antibody responses.
>In recent years, highly potent and/or broadly neutralizing human monoclonal antibodies (bnAbs) that are generated in chronic HIV-1 infections have been defined.
>These bnAbs exhibit atypical features such as extensive somatic hypermutations, long complementary determining region (CDR) lengths, tyrosine sulfation and presence of insertions/deletions, enabling them to effectively neutralize diverse HIV-1 viruses despite extensive variations within the core epitopes they recognize.
>As some of the HIV-1 bnAbs have evolved to recognize the dense viral glycans and cross-reactive epitopes (CREs), we assessed if these bnAbs cross-react with SARS-CoV-2.
>Several HIV-1 bnAbs showed cross-reactivity with SARS-CoV-2 while one HIV-1 CD4 binding site bnAb, N6, neutralized SARS-CoV-2. Furthermore, neutralizing plasma antibodies of chronically HIV-1 infected children showed cross neutralizing activity against SARS-CoV-2
>human monoclonal antibodies tolerating extensive epitope variability can be leveraged to neutralize pathogens with related antigenic profile
https://www.biorxiv.org/content/10.1101/2020.12.09.418806v1
A single dose, BCG-adjuvanted SARS-CoV-2 vaccine induces Th1-polarized immunity and high-titre neutralizing antibodies in mice
>we have exploited the immunostimulatory properties of bacille Calmette-Guerin (BCG), the vaccine for tuberculosis, to develop a SARS-CoV-2-specific and highly immunogenic vaccine candidate.
>Combination of BCG with a stabilized, trimeric form of the SARS-CoV-2 spike antigen promoted rapid development of virus-specific IgG antibodies in the sera of vaccinated mice, which could be further augmented by the addition of alum.
>This vaccine formulation, termed BCG:CoVac, induced a Th1-biased response both in terms of IgG antibody subclass and cytokine release by vaccine-specific CD4+ and CD8+ T cells.
>A single dose of BCG:CoVac was sufficient to induce high-titre SARS-CoV-2 neutralizing antibodies (NAbs) that were detectable as early as 2 weeks post-vaccination; NAb levels were greater than that seen in the sera of SARS-CoV-2-infected individuals.
>Boosting of BCG:CoVac-primed mice with a heterologous vaccine combination (spike protein plus alum) could further increase SARS-CoV-2 spike protein-specific antibody response.
>BCG:CoVac would be broadly applicable for all populations susceptible to SARS-CoV-2 infection and in particular could be readily incorporated into current vaccine schedules in countries where BCG is currently used
https://www.biorxiv.org/content/10.1101/2020.12.10.419044v1
Scientists have linked the most severe form of SARS2 with five genes that affect lung inflammation and the body’s ability to fight off viruses.
>Their findings, from a study of 2,700 Covid-19 patients in intensive care units across Britain, point to several existing drugs that could be repurposed to treat people who risk becoming critically ill.
>The genes – called IFNAR2, TYK2, OAS1, DPP9 and CCR2 – partially explain why some people become desperately sick with Covid-19, while others are not affected, said Kenneth Baillie of Edinburgh University, co-author of the study published on Friday in Nature.
>The new information should help scientists design clinical trials of medicines that target specific antiviral and anti-inflammatory pathways.
>Among those with the most potential, Baillie said, should be a class of anti-inflammatory drugs called JAK inhibitors, including Eli Lilly’s arthritis drug baricitinib, which has been found to help hospitalised pneumonia patients in combination with Gilead’s remdesivir.
https://archive.is/SXzIK
Long-term SARS-CoV-2 RNA shedding and its temporal association to IgG seropositivity
>Thefinding that the time to IgG seropositivity can be shorter than the lower bound ofpositive PCR tests in some patients, suggests that SARS-CoV-2-positive patients can continue to shed viral RNA for days or even weeks while generating IgG antibodies.
>days or even weeks while generating IgG antibodies
>weeks
https://journals.scholarsportal.info/pdf/20587716/v6inone/nfp_lsrsaitatis.xml
The D614G Mutation Enhances the Lysosomal Trafficking of SARS-CoV-2 Spike
>spike is trafficked to lysosomes and that the D614G mutation enhances the lysosomal sorting of spike and the lysosomal accumulation of spike-positive punctae in SARS-CoV-2-infected cells.
>Spike trafficking to lysosomes is an endocytosis-independent, vacuolar ATPase-dependent process, and spike-containing lysosomes drive lysosome clustering but display poor lysotracker labeling and reduced uptake of endocytosed materials.
>These results are consistent with the lysosomal pathway of coronavirus biogenesis and raise the possibility that a common mechanism may underly the D614G mutation's effects on spike protein trafficking in infected cells and the accelerated entry of SARS-CoV-2 into uninfected cells
>SARS-CoV-2 spike is trafficked to lysosomes
>lysosomes of spike-expressing cells accumulated in large clusters, a phenotype that was relatively uncommon in non-expressing cells
>This appearance is likely due to lysosome clustering rather than lysosome fusion: cells treated with vacuolin-1 contained swollen lysosomes several micrometers in diameter
>sizes and numbers of these lysosomes appeared to be similar in expressing and non-expressing cells, indicating that spike expression induces lysosome clustering rather than lysosome fusion
>Spike expression disrupts lysosome function
>Spike trafficking to lysosomes is resistant to inhibitors of endocytosis, microtubules, and secretion but sensitive to V-ATPase inhibition
https://www.biorxiv.org/content/10.1101/2020.12.08.417022v1
[reminder (read the contents of the link, preferably]
SARS-CoV-2 utilizes lysosomes to exit cells
https://archive.vn/03Y0A
Short of Breath for the Long Haul: Diaphragm Muscle Dysfunction in Survivors of Severe SARS-2 as Determined by Neuromuscular Ultrasound
>25 patients study from Chicago
>Many survivors from acute respiratory distress syndrome (ARDS) associated with coronavirus disease 2019 (COVID-19) suffer from persistent dyspnea and fatigue long after resolution of the active infection. In a cohort of 25 consecutive COVID-19 ARDS survivors admitted to an inpatient rehabilitation hospital (76% male),
>80% of them had at least one sonographic abnormality of diaphragm muscle structure or function.
>Specifically, when compared to established normative data,
>76% had impaired contractility (reduced thickening ratio), and
>20% patients had atrophy (reduced muscle thickness).
>These findings support neuromuscular respiratory dysfunction as a highly prevalent underlying cause for prolonged functional impairments after hospitalization for COVID-19.
>Currently, long term dysfunction in these patients is primarily attributed to lung parenchymal damage, overlooking diaphragm dysfunction as a possible contributor.
>Given that the diaphragm is the main respiratory muscle, we speculate that prolonged dysfunction may be a factor in at least a subset of patients.
https://www.medrxiv.org/content/10.1101/2020.12.10.20244509v1
An Immediate and Long-Term Complication of SARS-2 May Be Type 2 Diabetes Mellitus: The Central Role of β-Cell Dysfunction, Apoptosis and Exploration of Possible Mechanisms
https://archive.vn/ISwwE
Scientists discover how SARS-2 virus causes multiple organ failure in mice
>Within seven days post-infection, all of the mice with COVID-19 had stopped eating and were completely inactive, and had lost, on average, about 20% of their body weight. Animals that had been engineered to carry the human ACE2 protein but had not been infected with the virus, on the other hand, did not lose a significant amount of weight.
>Moreover, the COVID-19 infected animals had altered levels of immune cells, swelling of the heart tissue and wasting away of the spleen — all symptoms that have been observed in people who are critically ill with COVID-19.
>Deb’s team also looked at which genes were turned on and off in the mice infected with SARS-CoV-2, and they discovered other signs of disease. Common molecular processes that help cells generate energy — through mechanisms known as the tricarboxylic acid cycle, or TCA cycle, and electron transport chain — were shut off in the heart, kidney, spleen and lungs.
>Finally, the study also revealed that some changes were long-lasting throughout the organs in mice with COVID-19. In addition to temporarily altering which genes were turned on and off in some cells, the virus made epigenetic changes, that could explain why, in some people with COVID-19, symptoms persist for weeks or months after their bodies are rid of the virus.
https://archive.vn/bGCkV
SARS-CoV-2-Associated Neurological Disorders: The Potential Route of CNS Invasion and Blood-Brain Barrier Relevance"
https://archive.vn/ISwwE
SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis
>(?) No study detected live virus beyond day 9 of illness
https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(20)30172-5/fulltext
On kids-long-haulers
https://archive.vn/HbAcK
Role of favipiravir in the treatment of adult patients with moderate to severe SARS-2: a single-center, prospective, observational, sequential cohort study from Hungary
>Favipiravir did not seem to affect disease progression. Further data are needed to position this drug among the anti-SARS-CoV-2 armamentarium.
https://www.medrxiv.org/content/10.1101/2020.11.26.20238014v1
Characterising long-term SARS-2: a rapid living systematic review
https://www.medrxiv.org/content/10.1101/2020.12.08.20246025v1
A novel multi-omics-based identification of symptoms, comorbid conditions, and possible long-term complications in SARS-2
https://www.medrxiv.org/content/10.1101/2020.12.08.20245753v1
"SARS-CoV-2 infection associated with the recurrence of nephrotic syndrome in a 3 yea old Japanese boy"
https://archive.is/xidWr
Prior infection with seasonal coronavirus does not provide immunity to subsequent infection with SARS-CoV-2
>A sizable fraction of healthy blood donors have cross-reactive T cells to SARS-CoV-2 peptides due to prior infection with seasonal coronavirus. Understanding the role of cross-reactive T cells in immunity to SARS-CoV-2 has implications for managing the COVID-19 pandemic.
>We show that individuals with documented history of seasonal coronavirus have a similar SARS-CoV-2 infection rate and COVID-19 severity as those with no prior history of seasonal coronavirus.
>Our findings suggest prior infection with seasonal coronavirus does not provide immunity to subsequent infection with SARS-CoV-2
>https://www.medrxiv.org/content/10.1101/2020.12.04.20243741v1
Parkinsonism as a Third Wave of the SARS-CoV-2 Pandemic?
>There may be a myriad of potential long-term neurological and neuropsychiatric complications secondary to SARS-CoV-2 infection including a potential link to worsening parkinsonism in patients with PD and possibly even delayed neurological effects including parkinsonism. It remains to be seen whether COVID-19 viral infections will be later linked to parkinsonism as is the case in other viruses. Also, unlike many neurological conditions, such as neuropathy, there are emerging tools available to identify parkinsonism early in the disease process
https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd202211
SARS-CoV-2 and the risk of Parkinson's disease: facts and fantasy
>So far, 3 cases of parkinsonism have been reported after SARS-CoV-2 infection.
>two men aged 45 and 58 years, and a woman aged 35 years
>None of the male patients had a monogenic cause or known genetic predisposition for Parkinson's disease, while genetic tests were not done for the female patient. Onset was acute in the three cases (10–32 days after SARS-2 diagnosis); one patient (the 58 year old male) developed akinetic rigid syndrome in the context of a complex neurological presentation compatible with encephalopathy, including myoclonus and opsoclonus, while the other two patients had pure asymmetric akinetic-rigid features, with tremor, and mild respiratory disease.
>Functional nigrostriatal neuroimaging was abnormal in all three cases, which implies dopaminergic nigrostriatal impairment, but is not diagnostic of Parkinson's disease
https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(20)30442-7/fulltext
Ozone exposure upregulates the expression of host susceptibility protein TMPRSS2 to SARS-CoV-2
>unhealthy levels of ozone in the environment may predispose individuals to severe SARS-CoV-2 infection
>The TMPRSS2 protein and Tmprss2 transcripts were significantly elevated in the extrapulmonary airways, parenchyma, and alveolar macrophages from ozone-exposed mice. A significant proportion of additional known SARS-CoV-2 host susceptibility genes were upregulated in alveolar macrophages and parenchyma from ozone-exposed mice
https://www.biorxiv.org/content/10.1101/2020.11.10.377408v1
Targeting Lipid Rafts—A Potential Therapy for SARS-2
https://www.frontiersin.org/articles/10.3389/fimmu.2020.574508/full
SARS-CoV-2 in Brazil shows gross genetic diversity
>this could reduce the efficiency of some of the interventions meant to contain the virus, due to the viral genetic diversity
https://archive.vn/1evLg
https://archive.vn/rBL6X
Three-quarters attack rate of SARS-CoV-2 in the Brazilian Amazon during a largely unmitigated epidemic
>In conclusion, our data show that >70% of the population has been infected in Manaus approximately seven months after the virus first arrived in the city. This is above the theoretical herd immunity threshold. However, prior infection may not confer long-lasting immunity (30, 31). Indeed, we observed rapid antibody waning in Manaus, consistent with other reports that have shown signal waning on the Abbott IgG assay (14, 32). However, other commercial assays, with different designs or targeting different antigens, have more stable signal (14), and there is evidence for a robust neutralizing antibody response several months out from infection (33). Rare reports of reinfection have been confirmed (34), but the frequency of its occurrence remains an open question (35). Manaus represents a “sentinel” population, giving us a data-based indication of what may happen if SARS-CoV-2 is allowed to spread largely unmitigated.
https://science.sciencemag.org/content/early/2020/12/07/science.abe9728
[]
>Bioinformics study reveals P53 signaling, Genes NFKBIA, C3, CCL20 are among cellular pathways and genes affected by SARS-2.
https://www.thailandmedical.news/news/covid-19-research-bioinformatics-study-reveals-p53-signaling,-genes-nfkbia,-c3,-ccl20-are-among-cellular-pathways-and-genes-affected-by-coronavirus
SARS-CoV-2 infects cells following viral entry via clathrin-mediated endocytosis
>following engagement with the plasma membrane, SARS-CoV-2 undergoes rapid clathrin-mediated endocytosis. This suggests that transfer of viral RNA to the cell cytosol occurs from the lumen of the endosomal system, and importantly clathrin-heavy chain knockdown, which blocks clathrin-mediated endocytosis, reduces viral infectivity
https://www.biorxiv.org/content/10.1101/2020.07.13.201509v3
Neuropilin-1 helps SARS-CoV-2 get in
>short sequence from Spike attached to neuropilin-1
>SARS-CoV-2 was able to infect fewer cells if they used a small molecule called EG00229 or antibodies to block the Spike protein’s access to neuropilin-1
https://archive.vn/KtK1U
HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry
>high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacological SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible molecular connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 infection
https://archive.vn/szfXM
[]
Efficient inhibition of SARS-CoV-2 strains by a novel ACE2-IgG4-Fc fusion protein with a stabilized hinge region
>The novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) enters its host cells after binding the angiotensin-converting enzyme 2 (ACE2) via its spike glycoprotein.
>This interaction is critical for virus entry and virus-host membrane fusion.
>Soluble ACE2 ectodomains bind and neutralize the virus but the short in vivo half-lives of soluble ACE2 limits its therapeutic use.
>Fusion of the constant (Fc) part of human immunoglobulin G (IgG) to the ACE2 ectodomain can prolong the in vivo half-life but bears the risk of unwanted Fc-receptor activation and antibody-dependent disease enhancement.
>Here, we describe optimized ACE2-Fc fusion constructs that avoid Fc-receptor binding by using IgG4-Fc as a fusion partner.
>The engineered ACE2-IgG4-Fc fusion proteins described herein exhibit promising pharmaceutical properties and a broad antiviral activity at single-digit nanomolar concentration.
>In addition, they allow to maintain beneficial enzymatic activity of ACE2 and thus are very promising candidate antivirals broadly acting against coronaviruses
https://www.biorxiv.org/content/10.1101/2020.12.06.413443v1
Although the literature appears conflicting, large studies which account for covariates strongly suggest that HIV infection increases SARS-2 mortality
https://www.medrxiv.org/content/10.1101/2020.12.04.20240218v1
Paradoxical effects of cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) on SARS-CoV2 infection and disease
>ACE2 levels were decreased in both bronchial and alveolar epithelial cells from uninfected COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-treatment did not affect ACE2 levels but potently inhibited SARS-CoV-2 replication in this in vitro model. These findings urge to further investigate the controversial effects of CS and COPD on SARS-CoV2 infection
https://www.biorxiv.org/content/10.1101/2020.12.07.413252v1
People with asthma less likely to contract SARS-2: study
https://archive.vn/K17hS
Bioactive compounds found in green, black, and oolong tea possess remarkable antiviral activities against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
>Significant inactivation of SARS-CoV-2 by a green tea catechin, a catechin-derivative and galloylated theaflavins in vitro
>results strongly suggest that EGCG, and more remarkably TSA and galloylated theaflavins, inactivate the novel coronavirus
https://archive.vn/yZHA6
Long SARS-2 and the role of physical activity: a qualitative study
>To explore the lived experience of Long Covid with particular focus on the role of physical activity Design Qualitative study using semi-structured interviews Participants 18 people living with Long Covid (9 male, 9 female; aged between 18-74; 10 White British, 3 White Other, 3 Asian, 1 Black, 1 mixed ethnicity) recruited via a UK-based research interest database for people with Long Covid Setting Telephone interviews with 17 participants living across the UK and 1 participant living in the US Results Four themes were generated.
>Theme one highlights the physical and social isolation experienced by people with Long Covid, compounded by a lack of support and advice from medical professionals.
>Theme two describes how participants sought information and validation through online sources and communities.
>Theme three captures the challenges associated with managing physical and cognitive effects of Long Covid including fatigue and brain fog whilst trying to resume and maintain activities of daily living and other forms of exercise.
>Theme four illustrates the battle with self-concept to accept reduced function (even temporarily) and the fear of permanent reduction in physical and cognitive ability
https://www.medrxiv.org/content/10.1101/2020.12.03.20243345v1
Angelica archangelica plant roots and seeds - first-described recently discovered non-toxic vegetal-derived furocoumarin preclinical efficacy against SARS-CoV-2: a promising antiviral herbal drug
> ICEP4 purified compound (ICEP4) is a recently discovered furocoumarin-related purified compound coming from roots and seeds of Angelica archangelica (herbal drug)
>Successful ICEP4 doses against SARS-CoV-2-challenged cells are within the maximum threshold of toxicity concern (TTC) of furocoumarins as herbal preparation, stated by European Medicines Agency (EMA). Characteristic ICEP4 chemical compounding and its safe TTC let us to assume that an antiviral first-observed natural compound has been discovered. Potential druggability of a new synthetic ICEP4-related compound remains to be elucidated. However, well-established historical use of ICEP4-related compounds as herbal preparations may point towards an already-safe widely extended remedy, which may be ready-to-go for large-scale clinical trials under EMA emergency regulatory pathway. To the best of authors´ knowledge, ICEP4-related herbal drug can be postulated as a promising therapeutic treatment for COVID19
https://www.biorxiv.org/content/10.1101/2020.12.04.410340v1
https://www.biorxiv.org/content/10.1101/2020.12.04.410340v1.full.pdf
[chink study] SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2
>S protein alone can damage vascular endothelial cells (ECs) in vitro and in vivo, manifested by impaired mitochondrial function, decreased ACE2 expression and eNOS activity, and increased glycolysis. The underlying mechanism involves S protein downregulation of AMPK and upregulation of MDM2, causing ACE2 destabilization. Thus, the S protein-exerted vascular endothelial damage via ACE2 downregulation overrides the decreased virus infectivity
https://www.biorxiv.org/content/10.1101/2020.12.04.409144v1
https://www.biorxiv.org/content/10.1101/2020.12.04.409144v1.full.pdf
Circulating ACE2-expressing Exosomes Block SARS-CoV-2 Virus Infection as an Innate Antiviral Mechanism
>we detected circulating exosomes that express the SARS-CoV-2 viral entry receptor angiotensin-converting enzyme 2 (ACE2) in plasma of both healthy donors and convalescent COVID-19 patients
>We demonstrated that exosomal ACE2 competes with cellular ACE2 for neutralization of SARS-CoV-2 infection. ACE2-expressing (ACE2+) exosomes blocked the binding of the viral spike (S) protein RBD to ACE2+ cells in a dose dependent manner, which was 400- to 700-fold more potent than that of vesicle-free recombinant human ACE2 extracellular domain protein (rhACE2)
>As a consequence, exosomal ACE2 prevented SARS-CoV-2 pseudotype virus tethering and infection of human host cells at a 50-150 fold higher efficacy than rhACE2.
>A similar antiviral activity of exosomal ACE2 was further demonstrated to block wild-type live SARS-CoV-2 infection.
>Of note, depletion of ACE2+ exosomes from COVID-19 patient plasma impaired the ability to block SARS-CoV-2 RBD binding to host cells
https://www.biorxiv.org/content/10.1101/2020.12.03.407031v1
SARS-2 mortality will lower the U.S. life expectancy at birth (LEB) for 2020 by one full year. Such an impact on the U.S. LEB is unprecedented since the end of World War II
>the impact of Covid-19 on U.S. mortality can be expected to cancel a decade of gains against all other causes of mortality combined
https://www.medrxiv.org/content/10.1101/2020.12.03.20243717v1
Korean Study: Indoor SARS-CoV-2 Transmission from 21 Feet Away in Just 5 Minutes
https://archive.vn/2YhxN
SARS-CoV-2 both D614 and G614 spike variants impair neuronal synapses and exhibit differential fusion ability
https://www.biorxiv.org/content/10.1101/2020.12.03.409763v1
>Treatment of SARS-CoV-2 infection with a new antiviral drug, MK-4482/EIDD-2801 or Molnupiravir, completely suppresses virus transmission within 24 hours, researchers have discovered.
https://archive.vn/xQ7U1
"Post-infectious inflammatory disease in MIS-C features elevated cytotoxicity signatures and autoreactivity that correlates with severity"
https://www.medrxiv.org/content/10.1101/2020.12.01.20241364v1
"Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases"
https://jamanetwork.com/journals/jamacardiology/fullarticle/10.1001/jamacardio.2020.3551
"Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant"
https://pubmed.ncbi.nlm.nih.gov/32321524/
"The D614G mutation in SARS-CoV-2 Spike increases transduction of multiple human cell types"
https://pubmed.ncbi.nlm.nih.gov/32587969/
SARS-CoV-2 virions have been detected in the mucosa of patients with persistent SARS-2 3 months after the acute phase
https://twitter.com/doc_Moreno/status/1334518455723323394
Intact virions in the gastrointestinal tract (after 3 months)
https://www.biorxiv.org/content/10.1101/2020.11.03.367391v1
MIT study: Moderna, Pfizer, AstraZeneca and other vaccines may not do as well covering people of Black or Asian genetic ancestry as they do for white people
"Preliminary results suggest that, on average, people of Black or Asian ancestry could have a slightly increased risk of vaccine ineffectiveness," one of the study's authors wrote.
"[The] weakness [of the vacines], the MIT report contends, which is that they do not use a sufficiently diverse set of viral particles to stimulate the same level of immune response in all people in the population, depending on genetic makeup."
MIT release has finer point: Asians least likely to respond to covid vaccines.
"people whose cellular immune system is not predicted to robustly respond to the vaccine ranged from [<.5%] of white participants to nearly 10 percent of Asian participants."
https://www.zdnet.com/google-amp/article/mit-machine-learning-models-find-gaps-in-coverage-by-moderna-pfizer-other-warp-speed-covid-19-vaccines/
MIT study: Covid-19 vaccines may be less effective for Asian Americans
https://www.csail.mit.edu/news/mit-study-covid-19-vaccines-may-be-less-effective-asian-americans
De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2
https://science.sciencemag.org/content/370/6521/1208
New paper showing IFITMs inhibit SARS-CoV-2 endosomal entry, but IFITM3 conversely ENHANCES virus fusion at the plasma membrane. Distinct mechanisms at play. High TMPRSS2 shifts balance --> enhancement.
https://www.embopress.org/doi/abs/10.15252/embj.2020106501
https://www.biorxiv.org/content/10.1101/2020.08.11.246678v1.full
There could be a competition between Furin cleavage and heparan Sulfate binding
https://www.biorxiv.org/content/10.1101/2020.08.10.241414v1
IFITMs facilitate SARS-CoV-2 infection
https://www.biorxiv.org/content/10.1101/2020.08.18.255935v1
Lung cell infections
https://www.biorxiv.org/content/10.1101/2020.08.18.255935v1
Neutralizing antibody against SARS-CoV-2 spike in SARS-2 patients, health care workers and convalescent plasma donors
https://insight.jci.org/articles/view/143213/
Modeling Multi-organ Infection by SARS-CoV-2 Using Stem Cell Technology
https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30550-6
https://justpaste.it/img/4d35e54e8409e3dc30b7a195d68acdad.jpg
Reviewing findings from past studies that suggest CNS involvement of SARS-CoV-2
>Involvement of the nervous system in COVID-19: The bell should toll in the brain
https://www.sciencedirect.com/science/article/pii/S0024320520313217
https://justpaste.it/img/f6ee44430e77780fe4bfbd5ef9a0bf42.jpg
Researchers determine how the SARS-CoV-2 virus hijacks and rapidly causes damage to human lung cells
https://archive.vn/L7ebo
Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2
>SARS-CoV-2 infection in induced lung cells is characterized by phosphoproteomics
>Analysis of response reveals host cell signaling and protein expression profile
>Comparison to studies in undifferentiated cell lines shows unique pathology in iAT2s
>Systems-level predictions find druggable pathways that can impede viral life cycle
https://archive.vn/jlUJX
‘Matrix microscopy’: Powerful stargazing tech allows scientists to see directly through skulls without need for surgery
>Direct observation of live brains is difficult and requires invasive and dangerous surgery to cut through skin and bone. Now scientists can peer through skulls thanks to powerful technology borrowed from the field of astronomy.
>Porous and often inconsistent structures like bone tend to scatter light in unpredictable ways, frustrating efforts to ‘see’ through them using medical technology.
>However, scientists have now discovered a new method to create a clear image of what lies behind the skull from scattered infrared light shone by a laser.
>“Our microscope allows us to investigate fine internal structures deep within living tissues that cannot be resolved by any other means,” said physicists Seokchan Yoon and Hojun Lee from Korea University.
>The new imaging technology, known as laser-scanning reflection-matrix microscopy (LS-RMM), is so called because it derives a complete dataset of input-output response from the scattered laser light.
>In other words, some of the laser's photons can pass through the skull while others are scattered in a variety of different directions. The new process takes data derived from all of the photons into account to build a more complete picture of the brain behind the bone wall, by correcting any distortions.
>“This will greatly aid us in early disease diagnosis and expedite neuroscience research,” the researchers say.
>For now, one major drawback of the method is the sheer volume of computational power required to make sense of the reflection matrix. But the technique is still in its infancy and advances in computational power continue on a regular basis.
https://archive.vn/34WFO
Steam inhalation therapy found to inactivate SARS-CoV-2 virions
https://www.news-medical.net/news/20201130/Steam-inhalation-therapy-found-to-inactivate-SARS-CoV-2-virions.aspx
Emetine as an antiviral agent suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E: An in vitro study
>emetine targets SARS-CoV-2 protein synthesis which is mediated via inhibiting the interaction of SARS-CoV-2 RNA with eIF4E. This is a novel mechanistic insight on the antiviral efficacy of emetine. In vitro antiviral efficacy against SARS-CoV-2 and its ability to protect chicken embryos against IBV suggests that emetine could be repurposed to treat COVID-19
https://www.biorxiv.org/content/10.1101/2020.11.29.401984v1
The invasion of the CNS by SARS-CoV-2, as shown recently in areas like the brainstem that control the normal breathing process with nuclei like the pre-Bötzinger complex (pre-BÖTC), may explain why some of the patients with SARS-2, who have been reported to have recovered from pneumonia, could not be weaned from invasive mechanical ventilation and the occurrences of acute respiratory arrests seen in COVID-19
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422910/
Heart Failure Seen in Baby With SARS-2, MedPageToday
https://archive.is/f512F
A case of limbic encephalitis associated with asymptomatic SARS-2 infection
https://jnnp.bmj.com/content/91/11/1229
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The possible immunoregulatory and anti-inflammatory effects of selective serotonin reuptake inhibitors in coronavirus disease patients
https://www.sciencedirect.com/science/article/pii/S0306987720322489
Functions of serotonin in hypoxic pulmonary vascular remodeling.
https://hal.archives-ouvertes.fr/hal-01274919/document
Hypoxia-induced secretion of serotonin from intact pulmonary neuroepithelial bodies in neonatal rabbit
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2290169/
Post-COVID Parkinsonism
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273038/pdf/MDS-9999-na.pdf
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Asymptomatic patients have higher SARS-CoV-2 viral loads than symptomatic patients, study says
>researchers collected nasopharyngeal, oropharyngeal, oral cavity, rectal, saliva, urine, and blood samples from patients who were hospitalized due to COVID-19.
>A total of 360 samples from 60 patients were obtained upon admission. Of these, 25 percent did not have symptoms, while 75 percent were symptomatic.
>The Public Health Institute of Turkey Virology Reference and Research Laboratory analyzed the samples.
>The researchers found that vital loads of asymptomatic patients were higher when compared with symptomatic patients. Further, the viral load had a negative trend with increasing age, while a significant decrease in viral loads was seen with increasing disease severity.
>a significant decrease in viral load was observed with increasing disease severity,” the researchers wrote in the paper.
>The team noted that factors tied to a poor prognosis, including bilateral ground-glass opacity in chest X-ray, low lymphocyte count, and older age, are correlated with low SARS-CoV-2 viral load.
>“COVID-19 is a complicated puzzle with pieces of many colors and shapes. Further, virologic and immunological studies are urgently needed to put all the pieces together and see the big picture,” the researchers added.
https://archive.vn/nAgPQ
Roche receives FDA Emergency Use Authorization for new test to measure the level of SARS-CoV-2 antibodies
>Elecsys® Anti-SARS-CoV-2 S test specifically detects antibodies against the SARS-CoV-2 spike protein
>The spike protein is the target of many COVID-19 vaccines in development
>This test may help identify recovering patients who could potentially be serum and plasma donors for developing treatments for COVID-19
https://archive.vn/AJqzY
K460N and N501D are not found in any bat strains, including Ra strains. Y505H is not found in any other Ra infecting virii. Especially N501D. Experimentally, RaTG13 binds nothing.
>exceedingly well adapted to human ACE2
https://zenodo.org/record/3986406#.X8es2U_mg0H
"Prospective mapping of viral mutations that escape antibodies used to treat COVID-19"
>These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2, as well as in lab viral escape selections. Finally, the maps reveal that mutations escaping each individual antibody are already present in circulating SARS-CoV-2 strains
https://www.biorxiv.org/content/10.1101/2020.11.30.405472v1
The coronavirus SARS-CoV-2 can infect cells in the mouth, which may spur the virus's spread both in the body and to other people, according to a preliminary study.
>They found that, compared with other oral tissues, cells of the salivary glands, tongue and tonsils carry the most RNA linked to proteins that the coronavirus needs to infect cells. Namely, these include the ACE2 receptor, which the virus plugs into, and an enzyme called TMPRSS, which allows the virus to fuse its membrane with that of the host cell and slip inside.
>"Our study shows that the mouth is a route of infection as well as an incubator for the SARS-CoV-2 virus that causes COVID-19,"y, SARS-CoV-2 infection in the mouth could cause changes in saliva production or quality, contributing to symptoms of taste loss
>Byrd said. "However, we found these underappreciated but widely distributed salivary glands" — the so-called minor salivary glands — "can make their own virus after infection," he said. The team confirmed this by checking the levels of coronavirus RNA in the cells using PCR, a kind of test often used to detect and diagnose COVID-19, as well as a technique called in situ hybridization that also detects genetic material
https://www.livescience.com/oral-infection-coronavirus-spread.html
Persistent viral RNA positivity during recovery period of a patient with SARS-CoV-2 infection.
>Previous studies demonstrated that the salivary gland was a target of coronavirus infection and was an immune-privileged site of cytomegalovirus immune evasion and persistence.
>It is notable that an extremely high load of viral RNA was detected in saliva. Therefore, we hypothesize that the salivary gland is likely an immune-privileged site of SARS-CoV-2 persistence. The high load salivary virus may contaminate and spread to the respiratory tract and digestive tract. This may explain the positive throat swab and feces in the asymptomatic carriers and the patients recovered from the pneumonia.
https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25940
>These articles contributed 123 unique patients, with a total of 317 neurological events.
>Of these, 91 patients had grey matter changes, 95 patients had white matter changes and 72 patients had confirmed cerebral microbleeds.
https://www.medrxiv.org/content/10.1101/2020.10.21.20215640v1
SARS-CoV-2 infects brain astrocytes of SARS-2 patients and impairs neuronal viability
>median age 36
>Symptoms of anxiety were identified in approximately 28% of the subjects, and 20% of individuals presented symptoms of depression (Supplementary Fig. 1a). Abnormal performances were observed in nearly 28% of participants on logical memory and approximately 34% and 56% on TRAIL A and B
>Notably, SARS-CoV-2 genetic material and spike protein was detected in all of these five samples
>The presence of SARS-CoV-2 spike protein correlated with the presence of double-stranded RNA (dsRNA) in the infected cells (Fig. 2f), indicating replicative virus in the brain tissue.
>Overall, our findings evidence major alterations in brain cortex structure associated with neuropsychiatric symptoms as a consequence of COVID-19.
>We show that SARS-CoV-2 may infect almost one third of the cells in the brain and the majority of these cells are astrocytes
>In astrocytes, SARS-CoV-2 infection results in marked changes in cellular metabolism.
>Since astrocyte metabolism is key to support neuronal function, we hypothesized that these changes could indirectly impact neurons.
>We also found that SARS-CoV-2 infection elicits a secretory phenotype in astrocytes that results in increased neuronal apoptosis.
>we evaluated individuals that did not have to be hospitalized (i.e. had mild respiratory symptoms), and nevertheless, we observed notable alterations of cortical thickness.
https://www.medrxiv.org/content/10.1101/2020.10.09.20207464v2
https://www.medrxiv.org/content/10.1101/2020.10.09.20207464v2.full.pdf
The total number and mass of SARS-CoV-2 virions in an infected person
>We estimate that each infected person carries 109-1011 virions during peak infection, with a total mass of about 1 µg-0.1 mg, which curiously implies that all SARS-CoV-2 virions currently in the world have a mass of only 0.1-1 kg.
>Knowledge of the absolute number of virions in an infected individual can put into perspective parameters of the immune system response, minimal infectious doses and limits of detection in testing
https://www.medrxiv.org/content/10.1101/2020.11.16.20232009v1
https://www.medrxiv.org/content/10.1101/2020.11.16.20232009v1.full.pdf
SARS-CoV-2 utilizes lysosomes to exit cells and not normal biosynthetic secretory pathways.
https://archive.vn/03Y0A
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The ACE2-binding interface of SARS-CoV-2 Spike inherently deflects immune recognition
>we designed an RBD mutant that disrupts the ACE2IS and used it to characterize the prevalence of antibodies directed to the ACE2IS from convalescent sera of 94 COVID19-positive patients.
>We found that only a small fraction of RBD-binding antibodies targeted the ACE2IS.
>To assess the immunogenicity of different parts of the spike protein, we performed in vitro antibody selection for the spike and the RBD proteins using both unbiased and biased selection strategies.
>Intriguingly, unbiased selection yielded antibodies that predominantly targeted regions outside the ACE2IS, whereas ACE2IS-binding antibodies were readily identified from biased selection designed to enrich such antibodies.
>Furthermore, antibodies from an unbiased selection using the RBD preferentially bound to the surfaces that are inaccessible in the context of whole spike protein. These results suggest that the ACE2IS has evolved less immunogenic than the other regions of the spike protein
https://www.biorxiv.org/content/10.1101/2020.11.03.365270v1
16 new lineages of SARS-CoV-2 emerge in South Africa despite lockdown
>Published in a recent medRxiv* paper, researchers from South Africa, the United Kingdom, and Brazil found that these mutations in SARS-CoV-2 lineages are localized to South Africa. These unique strains, not found elsewhere in the world, are thought to have contributed around 42% to the country's total infection rate.
https://archive.vn/9Zisa
SARS-CoV-2 viroporin triggers NLRP3 inflammasome causing a severe inflammatory response
>the SARS-CoV-2 viroporin triggers the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome, which is responsible for the inflammatory pathology in severely ill COVID-19 patients
>the heightened inflammatory response results from the assembly and activation of a cell-intrinsic defense platform known as the inflammasome.
>The researchers assessed the influence of the SARS-CoV-2 ORF3a, which is thought to be a protein with ion channel activity (viroporin) that activates the NLRP3 inflammasome. ORF3a also plays a role in virus replication and the development of the disease.
>Viroporins are a group of proteins that participate in many viral functions, such as promoting the release of viral particles from cells. These proteins also affect cellular functions, including membrane permeability, glycoprotein trafficking, and the cell vesicle system. Though not essential for virus replication, some of these small proteins can generate pores that facilitate ion transport across cell membranes. As a result, they ensure virus release that can activate inflammasomes.
>Inflammasomes gather and respond to invading organisms as a component of the innate immune system. Hence, they form the first line of defense against invading pathogens and infection.
>SARS-CoV-2 ORF3a protein primes and activates the inflammasome through the efflux of potassium ions and the kinase NEK7. They also found that though the coronavirus ORF3a protein has separated from its homologs in other coronaviruses, some of the newly divergent residues are crucial for the activation of the NLRP3 inflammasome. Further, they are conserved in virus isolates across continents.
>Overall, the team noted that an essential viroporin needed for the release of SARS-CoV-2 from infected cells could also activate the NLRP3 inflammasome.
https://archive.vn/EOarT
Shorter androgen receptor polyQ alleles protect against life-threatening SARS-2 disease in males.
>Using host whole-exome sequencing data, we compared extreme phenotypic presentations (338 severe versus 300 asymptomatic cases) of the entire (men and women) Italian GEN-COVID cohort of 1178 subjects infected with SARS-CoV-2. We then applied the LASSO Logistic Regression model on Boolean gene-based representation of the poly-amino acids variability. Findings Shorter polyQ alleles (≤22) in the androgen receptor (AR) conferred protection against a more severe outcome in COVID-19 infection. In the subgroup of males with age <60 years, testosterone was higher in subjects with AR long-polyQ (≥23), possibly indicating receptor resistance (p=0.004 Mann-Whitney U test). Inappropriately low testosterone levels for the long-polyQ alleles predicted the need for intensive care in COVID-19 infected men. In agreement with the known anti-inflammatory action of testosterone, patients with long-polyQ (≥23) and age>60 years had increased levels of C Reactive Protein (p=0.018)
https://www.medrxiv.org/content/10.1101/2020.11.04.20225680v1
Longitudinal testing for respiratory and gastrointestinal shedding of SARS-CoV-2 in day care centres in Hesse, Germany. Results of the SAFE KiDS Study
>We conducted a longitudinal study over a period of 12 weeks (18th of June 2020 to 10th of September, 2020) to screen attendees and staff from day care centres in the state of Hesse, Germany, for both respiratory and gastrointestinal shedding of SARS-CoV-2. 825 children (age range 3 months to 8 years) and 372 staff members from 50 day care centres, which were chosen representatively from throughout the state, participated in the study. Parents were asked to perform both a buccal mucosa and an anal swab on their children once a week. Staff were asked to self-administer the swabs. RT-PCRs for SARS-CoV-2 were performed in a multiple-swab pooling protocol. Findings 7,366 buccal mucosa swabs and 5,907 anal swabs were analysed. No respiratory or gastrointestinal shedding of SARS-CoV-2 was detected in any of the children. Shedding of SARS-CoV-2 could be detected in two staff members from distinct day care centres. One was asymptomatic at the time of testing, and one was symptomatic
https://www.medrxiv.org/content/10.1101/2020.11.02.20223859v1
>hypothermia like 30% of the cases describe what they call it having a "cold fever" rather than "hot fever"
>it seems like a case was reported with acute hypothermia back in june
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305886/
SLAMF7 engagement super-activates macrophages in acute and chronic inflammation
>Macrophages regulate protective immune responses to infectious microbes, but aberrant macrophage activation frequently drives pathological inflammation. To identify regulators of vigorous macrophage activation, we analyzed RNA-seq data from synovial macrophages and identified SLAMF7 as a receptor associated with a super-activated macrophage state in rheumatoid arthritis. We implicated IFN-gamma as a key regulator of SLAMF7 expression. Engaging this receptor drove an exuberant wave of inflammatory cytokine expression, and induction of TNF-alpha following SLAMF7 engagement amplified inflammation through an autocrine signaling loop. We observed SLAMF7-induced gene programs not only in macrophages from rheumatoid arthritis patients, but in gut macrophages from active Crohn's disease patients and lung macrophages from severe COVID-19 patients.
https://www.biorxiv.org/content/10.1101/2020.11.05.368647v1
Th1 Dominant Nucleocapsid and Spike Antigen-Specific CD4+ and CD8+ Memory T Cell Recall Induced by hAd5 S-Fusion + N-ETSD Infection of Autologous Dendritic Cells from Patients Previously Infected with SARS-CoV-2
>Recognition of hAd5 S-Fusion + N-ETSD vaccine antigens by T cells from previously SARS-CoV-2 infected patients, together with the ability of this vaccine candidate to elicit de novo immune responses in naive mice suggests that it re-capitulates the natural immune response to SARS-CoV-2 to activate both B and T cells towards viral neutralization and recognition of infected cells, critical for prevention of COVID-19 disease. Intriguingly, our hAd5 S-Fusion + N-ETSD T-cell biased vaccine has the potential to not only provide protection for uninfected individuals, but also to be utilized as a therapeutic for already infected patients to induce rapid clearance of the virus by activating T cells to kill the virus-infected cells, thereby reducing viral replication and lateral transmission.
https://www.medrxiv.org/content/10.1101/2020.11.04.20225417v1
Effectiveness of an Ozone Disinfecting and Sanitizing Cabinet to Decontaminate a Surrogate Virus for SARS-CoV-2 on N-95 Masks
https://www.medrxiv.org/content/10.1101/2020.11.04.20226233v1
Vascular Thrombosis in SARS-2: A Potential Association with Antiphospholipid Antibodies. A Rapid Systematic Review
>Hospitalized patients with COVID-19 showed a higher prevalence of lupus anticoagulant compared to non-COVID-19 patients. Temporally, lupus anticoagulant was generally positive early in the course of illness, whereas anti-cardiolipin and anti-β2-glycoprotein-1 antibodies appeared to emerge later in the disease.
>Some patients who were aPL-negative at an early time-point after disease onset became aPL-positive at a later time-point. Lupus anticoagulant was independently associated with thrombosis in 60 COVID-19 patients in New York had who had 32 thrombotic events (8 arterial and 24 venous).
>In 88 patients in Wuhan, who had more than 20 each of arterial and venous thrombotic events, medium/high positivity for multiple aPL was significantly associated with arterial thrombosis.
>However, the association of aPL with thrombosis was not evident in reports that had an overall lower number of or predominantly venous thrombotic events. Analysis of pooled patients revealed that aPL were significantly more frequent in COVID-19 patients with stroke than stroke patients in the general population.
>Furthermore, injection of IgG aPL fractions from COVID-19 patients into mice accelerated venous thrombosis.
https://www.medrxiv.org/content/10.1101/2020.11.02.20224642v1
https://clinicaltrials.gov/ct2/show/NCT04391179
https://stm.sciencemag.org/content/early/2020/11/02/scitranslmed.abd3876
CSF of SARS-CoV-2 patients with neurological syndromes reveals hints to understand pathophysiology
>Our results do not show obvious SARS-CoV-2 infection of the central nervous system, but point to a mild inflammatory reaction reflecting an astrocytic reaction
https://www.medrxiv.org/content/10.1101/2020.11.01.20217497v1
Neuropathological Changes in Autopsied Brain Tissue of Patients With SARS-2
>post-mortem case series
>median age, 76 years
>Ischemic lesions in the brain were documented in 6 (14%) patients, and astrogliosis in 37 (86%) patients in the studied regions of the brain.
>Activation of microglia and infiltration by cytotoxic T lymphocytes were most pronounced in the brainstem and cerebellum. Meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. Study researchers observed a high degree of astrogliosis and microgliosis in the olfactory bulb, but only minor infiltration by cytotoxic T lymphocytes.
>SARS-CoV-2 RNA or proteins were detected in brain tissues of 21 (53%) patients, and both were identified in 8 (20%) patients. SARS-CoV-2 viral proteins were found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem.
>There was no association observed between the presence of SARS-CoV-2 virus in the central nervous system and the severity of neuropathological changes in the brain.
https://www.neurologyadvisor.com/topics/general-neurology/neuropathological-changes-in-autopsied-brain-tissue-of-patients-with-covid-19/
Dopamine-release mechanisms in the brain may play a major role in SARS-CoV-2 infection
>it is possible that after the initial binding or attachment of the SARS-CoV2 to ACE2 receptors, the spike protein of the virus binds to dopaminergic receptors of adjacent cells. Since the brain has dopamine receptors, it plays an integral regulatory role in local immunity, such as the release of lymphocytes and cytokines
>dopamine at certain concentrations can disrupt lymphocytic function. When there is an influx of dopamine, it further decreases both innate and adaptive immunity. This causes neural symptoms, including fatigue, dizziness, encephalopathy, and loss of consciousness
>Dopamine is also a regulator of immune function. The virus may manipulate the immune system by elevating the levels of dopamine to help them enter cells
>Further, the elevated production and release of D1-like receptors cause increased expression of cAMP, which causes a lowered innate immune response. On the other hand, the elevated expression of D2-like receptors causes a cytokine storm, which lowers the adaptive immune response
>research team also revealed that elevated dopamine levels reduce oxygen levels, which is often seen in patients with COVID-19. Dopamine can blunt the ventilatory response of the human basal carotid body activity to hypoxia
>SARS-CoV-2 and dopamine could be responsible for impaired ventilation in patients
>researchers noted three drugs among the ten tested drugs in a study that influences dopamine secretion. One of the drugs was shown to have the most beneficial outcome after Chinese researchers tested over 2,000 drugs in vitro. All the medicines that act as dopamine antagonists showed the potential to interact with the coronavirus.
https://archive.vn/MEUZK
Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies
>We measured anti- Spike antibody levels with the S-Flow assay and mapped SARS-CoV-2 Spike- and N-targeted regions by Luminex. Neutralization, complement deposition and Antibody-Dependent Cellular Cytotoxicity (ADCC) were evaluated using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC and trigger complement deposition. Antibody levels and activities are slightly lower in asymptomatic individuals. The different functions of the antibodies are correlated, independently of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction, with minor variations
>asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells. - Sera from convalescent COVID-19 patients activate the complement and kill infected cells by ADCC. - Asymptomatic and symptomatic SARS-CoV-2-infected individuals harbor polyfunctional antibodies. - Antibody levels and functions are slightly lower in asymptomatic individuals - The different antiviral activities of anti-Spike antibodies are correlated regardless of disease severity. - Functions of anti-Spike antibodies have similar kinetics of induction and contraction.
https://www.medrxiv.org/content/10.1101/2020.11.12.20230508v1
https://www.medrxiv.org/content/10.1101/2020.11.12.20230508v1.full.pdf
Preliminary Data from Real-World Study Demonstrate T-cell Testing Outperforms Antibody Testing in Identifying Past SARS-CoV-2 Infections
>Data support mounting evidence that measuring T-cells is necessary to fully characterize immune responses to SARS-CoV-2 across the population
>Additional supporting data to be published soon
https://archive.vn/NKLoM
Heating, ventilation and air-conditioning systems in the context of SARS-CoV-2: first update
>Four bundles of non-pharmaceutical interventions (NPIs) should be considered to reduce potential airborne transmission of SARS-CoV-2 in closed spaces: the control of SARS-2 sources in closed spaces; engineering controls in mechanically ventilated (by HVAC systems) and naturally ventilated closed spaces; administrative controls; and personal protective behaviour.
https://www.ecdc.europa.eu/en/publications-data/heating-ventilation-air-conditioning-systems-covid-19
Study comparing age matched COVID-19 +ve & -ve men (N=181, median age 38) found +ve men had ~half the ratio of testosterone:LH (p<0.0001), an indicator of early stage hypogonadism.
>"Testes may run high risk of damage and dysregulation under COVID-19."
https://www.medrxiv.org/content/10.1101/2020.03.21.20037267v1
[chink study] Impaired spermatogenesis in SARS-2 patients
[!] Funding
>This study was supported by Ministry of Science and Technology of China Plan, Hubei Science and Technology Plan, National Key Research and Development Program of China, HUST COVID-19 Rapid Response Call, China and National Natural Science Foundation of China; these funding bodies are public institutions, and they had no role in study conception, design, interpretation of results, and manuscript preparation.
>1st study: The age of the COVID-19 and control patients ranges from 51 to 83 (69.3±11.5) and 56 to 85 years (69.0±9.4)
>2nd study: The age of COVID-19 patients and controls ranges from 27 to 55 years old (40.8±8.5) and 30 to 54 years (40.1±5.8)
>Autopsied testicular and epididymal specimens of COVID-19 showed the presence of interstitial edema, congestion, red blood cell exudation in testes, and epididymides. Thinning of seminiferous tubules was observed. The number of apoptotic cells within seminiferous tubules was significantly higher in COVID-19 compared to control cases. It also showed an increased concentration of CD3+ and CD68+ in the interstitial cells of testicular tissue and the presence of IgG within seminiferous tubules. Semen from COVID-19 inpatients showed that 39.1% (n=9) of them have oligozoospermia, and 60.9% (n=14) showed a significant increase in leucocytes in semen. Decreased sperm concentration, and increased seminal levels of IL-6, TNF-α, and MCP-1 compared to control males were observed.
>Impairment of spermatogenesis was observed in COVID-19 patients, which could be partially explained as a result of an elevated immune response in testis
>However, no obvious difference of these parameters was observed between the mild cases and ordinary cases, or between the cases with or without a history of high fever (≥39 °C), maybe due to the limited size of patients
https://archive.vn/iqnXG
SARS-CoV-2 causes a different cytokine response compared to other cytokine storm-causing respiratory viruses in severely ill
https://www.medrxiv.org/content/10.1101/2020.11.14.20231878v1
https://www.medrxiv.org/content/10.1101/2020.11.14.20231878v1.full.pdf
Severe SARS-2 Is Fueled by Disrupted Gut Barrier Integrity
>Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback.
>SARS-2 severity and associated mortality are linked to higher tight junction permeability and higher translocation of bacterial and fungal products to the blood
>This intestinal disruption and microbial translocation correlate strongly with increased systemic inflammation and complement activation, lower gut metabolic function, and higher mortality
>Zonulin is the only known physiological mediator of tight junction permeability in the digestive tract, where higher levels of zonulin drive increases in tight junction permeability.
>hospitalized individuals with higher plasma levels of zonulin were more likely to die compared to those with lower levels of zonulin
>We also found higher levels of β-glucan, a polysaccharide cell wall component of most fungal species and a marker of fungal translocation, in individuals with severe SARS-2 compared to those with mild SARS-2 or controls
https://www.medrxiv.org/content/10.1101/2020.11.13.20231209v1
https://www.medrxiv.org/content/10.1101/2020.11.13.20231209v1.full.pdf
Goblet cells are prime target for SARS-CoV-2, study finds
>in the airway of patients with chronic obstructive pulmonary disease (COPD), a type of airway epithelial cell – called a goblet cell – presents a prime target for the virus and plays a vital role in promoting viral replication in this tissue.
>The lowest expression of ACE2 is in the blood, spleen and bone marrow, as well as the brain, blood vessels and muscle tissue.
>In the lungs, which are the primary site of the disease, the type II alveolar cells are chiefly observed to express ACE2, which is also found on ciliated cells. Goblet cells are also found abundantly in the bronchial epithelium, and these cells primarily produce mucin. Mucin is vital to trap disease-causing germs, dust and particles, which are then cleared away by the body’s cilia.
>Goblet cells in the nose and subsegmental bronchi also show ACE2 expression – at higher levels than on ciliated cells, in fact. This could explain how SARS-CoV-2 infects these cells preferentially, like the influenza A virus. This could also be why SARS-CoV-2 RNA (viral genetic material) is found in sputum, and why it can spread more rapidly between people than the earlier SARS-CoV that infected only ciliated cells
>COPD is an important risk factor for severe COVID-19, which prompted the current study on airway epithelium using both healthy and COPD-affected lung cells.
>Goblet cells show a rapid growth in number in COPD patients as well
>ACE2 and TMPRSS2 were expressed at higher levels in COPD epithelium because of the goblet cell hyperplasia (increased proliferation of goblet cells).
>researchers found that the virus preferentially infects goblet cells, because of their high expression of both ACE2 and TMPRSS2. The extent of infection was therefore greater in COPD epithelium compared to healthy epithelium
https://archive.vn/0r7sw
SARS-CoV-2 infection suppresses ACE2 function and antiviral immune response in the upper respiratory tract of infected patients
https://www.biorxiv.org/content/10.1101/2020.11.18.388850v1
SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues
https://www.thailandmedical.news/news/latest-research-shows-that-sars-cov-2-suppresses-ace2-activity-in-covid-19-patients-while-inducing-expression-of-the-interferon-stimulated-genes-isgs
Research in monkeys and cell cultures suggests that a common enzyme called catalase may be effective in treating SARS-2
https://web.archive.org/web/20201005195635/https://www.medicalnewstoday.com/articles/could-a-common-antioxidant-enzyme-help-treat-covid-19
How the SARS-2 Vaccine Can Destroy Your Immune System
https://www.europereloaded.com/how-the-covid-19-vaccine-can-destroy-your-immune-system/
SARS-2 vaccines designed to elicit neutralizing antibodies may sensitize vaccine recipients to more severe disease than if they were not vaccinated. Vaccines for SARS, MERS and RSV have never been approved, and the data generated in the development and testing of these vaccines suggest a serious mechanistic concern: that vaccines designed empirically using the traditional approach (consisting of the unmodified or minimally modified coronavirus viral spike to elicit neutralizing antibodies), be they composed of protein, viral vector, DNA or RNA and irrespective of delivery method, may worsen COVID‐19 disease via antibody‐dependent enhancement (ADE). This risk is sufficiently obscured in clinical trial protocols and consent forms for ongoing COVID‐19 vaccine trials that adequate patient comprehension of this risk is unlikely to occur, obviating truly informed consent by subjects in these trials.
>Conclusions drawn from the study and clinical implications
The specific and significant COVID‐19 risk of ADE should have been and should be prominently and independently disclosed to research subjects currently in vaccine trials, as well as those being recruited for the trials and future patients after vaccine approval, in order to meet the medical ethics standard of patient comprehension.
https://onlinelibrary.wiley.com/doi/10.1111/ijcp.13795
>One of the first spectroscopic imaging-based studies of neurological injury in COVID-19 patients has been reported by researchers at Massachusetts General Hospital (MGH) in the American Journal of Neuroradiology. Looking at six patients using a specialized magnetic resonance (MR) technique, they found that COVID-19 patients with neurological symptoms show some of the same metabolic disturbances in the brain as other patients who have suffered oxygen deprivation (hypoxia) from other causes, but there are also notable differences.
>Magnetic Resonance Spectroscopy (MRS) can identify neurochemical abnormalities even when structural imaging findings are normal. COVID-19 patients’ brains showed N-acetyl-aspartate (NAA) reduction, choline elevation and myo-inositol elevation, similar to what is seen with these metabolites in other patients with white matter abnormalities (leukoencephalopathy) after hypoxia without COVID. One of the patients with COVID-19 who showed the most severe white matter damage (necrosis and cavitation) had particularly pronounced lactate elevation on MRS, which is another sign of brain damage from oxygen deprivation.
https://archive.vn/QJcDH
>Scientists have unraveled one of the mysteries of Covid-19, why the virus strikes down older people while seeming to leave children untouched. The breakthrough could pave the way for new treatments to combat the pandemic.
>Researchers at Vanderbilt University Medical Center figured out that children have lower levels of a receptor protein that SARS-CoV-2 – the virus that causes Covid-19 – needs to invade the lungs.
https://www.rt.com/news/506707-scientists-decode-children-spared-covid19/
Infection by the new coronavirus SARS-CoV-2 (COVID-19 infection) is a multi-systemic illness [1]. Cardiac injury has been reported in 20% to 30% of hospitalised patients
https://archive.is/lcfoc
Pathophysiological mechanisms of liver injury in COVID‐19
https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.14730
SARS-CoV-2-Related Kidney Injury: Current Concern and Challenges
>Many studies have confirmed that comorbidities are important risk factors for the severity and outcome of SARS-CoV-2 infection [1]. Chronic kidney disease (CKD) [2] is not uncommon and represents one of the chronic diseases witnessed during COVID-19 ranging from 8.5 to 9.8% so far reported
https://archive.is/lWjQ9
These SARS-2 symptoms could last for months
>In research done by the CDC at the end of July, over 30 percent of COVID-19 patients had not returned to normal health conditions two or three weeks after testing. Out of respondents between the ages of 18 and 34, who typically have milder cases of illness, one in four still hadn’t full recovered weeks after testing. Even some children were still feeling the infection take a toll on their health months after infection. And the symptoms were far-ranging, from depression to myocarditis.
>“The fact that 78% of ‘recovered’ [patients] had evidence of ongoing heart involvement means that the heart is involved in a majority of patients, even if Covid-19 illness does not scream out with the classical heart symptoms, such as anginal chest pain,” Valentina Puntmann, a University Hospital Frankfurt cardiologist and author of the study, told STAT News.
>Natalie Lambert, a health researcher at Indiana University School of Medicine, found after surveying over 1,500 “long-haulers” on Facebook that hundreds of respondents struggled with anxiety, concentration, and depression.
>Even without physical symptoms, mental health consequences can take a serious toll on both survivors and anyone currently feeling overwhelmed by the state of the pandemic. For this symptom in particular, we all are at risk whether our bodies have been healthy or sick.
https://newsopener.com/science/these-covid-symptoms-could-last-for-months/
Rescue therapy with inhaled nitric oxide and almitrine in SARS-2 patients with severe acute respiratory distress syndrome
>In this pilot study of severe C-ARDS patients, iNO–almitrine combination was associated with rapid and significant improvement of oxygenation
https://archive.is/j53rj
>In dry indoor places i.e., less humidity (< 40% RH), the chances of airborne transmission of SARS-CoV-2 are higher than that of humid places (i.e., > 90% RH).
https://aaqr.org/articles/aaqr-20-06-covid-0302
>our findings suggest that declines in absolute humidity are likely to contribute to increased transmission of SARS-CoV-2
https://www.medrxiv.org/content/10.1101/2020.10.30.20223446v1
Estimated Airborne Decay of SARS-CoV-2 Calculator
https://www.dhs.gov/science-and-technology/sars-airborne-calculator
https://www.medrxiv.org/content/10.1101/2020.11.13.20231472v1
Airborne SARS-CoV-2 particles found up to 50M in a hospital ventilation system
>A study from Sweden investigated the potential of long-distance aerosol transmission of SARS-CoV-2 in a hospital setting via its ventilation system. The group tested for SARS-CoV-2 virus particles across a sample of ventilation system air filters located at various distances away from COVID-19 wards. The study concluded … “Here we present further evidence for SARS-CoV-2 ability to disperse from patients to ward vent openings as well as detection of viral RNA in ventilation exhaust filters located at least 50 meters from patient room vent openings. Although we could not conclude that the viral samples in this collection retained infective ability, the distance at which we detected RNA suggests that there may be a risk for airborne dissemination and transmission, especially at much closer distances to contagious persons in confined spaces, both in and outside hospital environments.”
https://archive.vn/Qriik
SARS-CoV-2-specific IgM / IgG responses accurately predict SARS-2 outcome
>The team found that high level of IgM against ORF7b at the time of hospitalization is an independent predictor of patient survival, while IgG response levels to 6 non-structural proteins - NSP4, NSP7, NSP9, NSP10, RdRp (NSP12), NSP14 - and 1 accessory protein - ORF3b - is a significant predictor of patient mortality.
>These results were accurate even after adjustments for comorbidities, demographics, and common lab markers for disease severity. Spline regression analysis showed that the correlation between NSP9 IgG, ORF7b IgM, and NSP10 IgG and COVID-19 mortality risk is linear. Their areas under curve for predictions were determined using computational cross-validations and were 0.74, 0.66, and 0.68, respectively.
https://archive.vn/HHYI8
Neo7Logix SARS-2 Treatment Reduces Viral Infection by More Than 99% in Preclinical Study
>the company has developed an approach to design highly effective specific-matched Anti-Viral Peptide (AVP) sequences that can be used for the treatment and prevention of novel pathogen diseases. A patent-pending method is used to design a pool of synthetic peptides that act in a multi-mechanistic approach to inhibit virus entry points, prevent viral endocytosis (membrane engulfing), block viral unpacking and replication and stimulate the long-term immune response and eradication of the virus.
>This “Precision-Based Immuno-Molecular Augmentation (PBIMA)” design method uses artificial intelligence to guide the design of anti-viral peptides based on the target viral genome sequences and available data on the human population HLA (human leukocyte antigen) susceptibility. Neo7Logix has recently completed a preclinical study that demonstrated greater than 99% reduction of viral load in mice infected with mutant coronavirus HCoV-229E using anti-HCoV-229E (COVID-19) PBIMA-SOLVx with no adverse effects. This proof of concept study also revealed remarkable immunomodulatory stimulation of T and B cells for the immune response. Dr. Catanzaro added, “to our knowledge, there currently is no other highly effective treatment for COVID-19.”
>The AVP had no Antibody-Dependent Enhancement (ADE) problem because it induced only CD8+/CD4+ response unlike some current prophylactic vaccines in clinical trials. Existing preclinical data along with computational results show that the AVP designs are non-toxic, non-allergenic and thermostable.
https://archive.vn/iXO0X
Israeli study about long-term effects on smell and taste.
https://www.medrxiv.org/content/10.1101/2020.09.25.20201343v2.full.pdf
>The most recent version of this unique organoid is based entirely on human stem cells, known to repair the deepest parts of our lungs. When the researchers exposed it to SARS-CoV-2, the results were illuminating.
>Known as alveoli, these balloon-like sacs have shown diffuse damage in fatal cases of COVID-19, and while this havoc is often attributed to a storm of immune cells called cytokines.
>The unique organoid includes just one type of lung stem cell, known as an alveolar type 2 epithelial cell (AT2), which has the ability to self-renew, differentiate into other lung cells, keep the sac open with surfactants, and directly bind to viruses.
When the SARS-CoV-2 virus was introduced into this organoid's dish, researchers say the virus quickly infected the AT2 cells and spread throughout the alveoli-like structure.
>The infection also triggered an inflammatory response in the organoid, reducing the production and proliferation of surfactant and inducing cell death, sometimes in surrounding areas that hadn't even yet been touched by the virus.
>"It was thought cytokine storm happened due to the large influx of immune cells, but we can see it also happens in the lung stem cells themselves,"
researchers found that administering low doses of interferons before infection slowed the spread of the virus, whereas reducing interferons before infection worsened the damage.
>This suggests interferons are somehow mediating the immune response in our alveoli, slowing the cascade of cell death as the lung tries to get ahead of the infection
https://archive.vn/zdcj4
CRISPR-Based Screen Identifies Host Factors for SARS-CoV-2
>top-ranked genes—those whose loss reduces viral infection substantially—clustered into a handful of protein complexes, including vacuolar ATPases, Retromer, Commander, Arp2/3, and PI3K. Many of these protein complexes are involved in trafficking proteins to and from the cell membrane
>While researchers performed the CRISPR screen using human lung cells, the team also explored whether the expression of required host genes was lung-specific or more broadly expressed. Among the top-ranked genes, only ACE2, the receptor known to be responsible for binding the SARS-CoV-2 viral protein Spike, showed tissue-specific expression, with the rest of the top gene hits broadly expressed across many tissues, suggesting that these mechanisms may function independent of cell or tissue type
>several of the top-ranked host genes directly interact with the virus’s own proteins, highlighting their central role in the viral lifecycle
>Using a recently-developed technology that couples large-scale CRISPR editing with single-cell RNA-sequencing (ECCITE-seq), the team identified that loss of several top-ranked genes results in upregulation of cholesterol biosynthesis pathways and an increase in cellular cholesterol. Using this insight, they studied the effects of amlodipine, a drug that alters cholesterol levels.
>amlodipine, a calcium-channel antagonist, upregulates cellular cholesterol levels and blocks SARS-CoV-2 infection. Since recent clinical studies have also suggested that patients taking calcium-channel blockers have a reduced COVID-19 case fatality rate, an important future research direction will be to further illuminate the relationship between cholesterol synthesis pathways and SARS-CoV-2
https://archive.vn/rcwTM
https://archive.vn/fqwHN
SARS-CoV-2 might attack red marrow and block new erythrocytes formation
> the virus might attack red marrow, thus being detrimental not only for erythrocytes in the bloodstream but also for the process of the formation of the new ones
>Lost of erythrocytes might cause damage to the brain neurons, blood vessels, and internals, considering they get not enough oxygen. In the most severe cases, multiple organ failure can occur, and without his own red blood cells, the patient starts to suffocate. Artificial ventilation doesn't help following there is no one who transports oxygen within the body. Effective therapy for such patients is to administer erythrocyte mass and vitamin B12
>Early breakdown of red blood cells is the initial reaction of the body to the SARS COV-2 virus, which scales up gradually. The patient can learn about the pathology by feeling the taste of iron. That occurs because hemoglobin released from erythrocytes in the bloodstream is get in saliva.
>everyone who has low hemoglobin is at risk. First of all, these are elderly people, patients with high blood pressure, people with obesity and diabetes mellitus, pregnant women, patients with primary and acquired immunodeficiency, with inhibition of hematopoietic function, HIV- and cancer patients.
>SARS-2 also induces destruction of white pulp in the spleen, the very tissue producing cells responsible for infectious immunity like T-cells, and B-lymphocytes. For this exact reason, secondary infections comorbid to SARS-2 are dangerous to humans. The body simply has nothing to fight back. A patient can survive only through large doses of antibiotics, while the main thing is not to be late
https://archive.vn/GK9ET
>Major new lineages of SARS-CoV-2 emerge and spread in South Africa during lockdown.
https://www.medrxiv.org/content/10.1101/2020.10.28.20221143v1
Study shows how exercise stalls cancer growth through the immune system
>Physical activity changes the metabolism of the immune system's cytotoxic T cells and thereby improves their ability to attack cancer cells. The study is published in the journal eLife.
>researchers divided mice with cancer into two groups and let one group exercise regularly in a spinning wheel while the other remained inactive. The result showed that cancer growth slowed and mortality decreased in the trained animals compared with the untrained.
>Next, the researchers examined the importance of cytotoxic T cells by injecting antibodies that remove these T cells in both trained and untrained mice. The antibodies knocked out the positive effect of exercise on both cancer growth and survival, which according to the researchers demonstrates the significance of these T cells for exercise-induced suppression of cancer.
>The researchers also transferred cytotoxic T cells from trained to untrained mice with tumors, which improved their prospects compared with those who got cells from untrained animals.
>To examine how exercise influenced cancer growth, the researchers isolated T cells, blood and tissue samples after a training sessions and measured levels of common metabolites that are produced in muscle and excreted into plasma at high levels during exertion. Some of these metabolites, such as lactate, altered the metabolism of the T cells and increased their activity. T cells isolated from an exercised animal showed an altered metabolism compared to T cells from resting animals.
>researchers examined how these metabolites change in response to exercise in humans. They took blood samples from eight healthy men after 30 minutes of intense cycling and noticed that the same training-induced metabolites were released in humans.
https://archive.vn/QEnT4
Some Coronavirus Long Haulers Have Skin Problems, ‘COVID Toes’ Months After Infection
>Researchers looked at nearly 1,000 patients with skin issues and said the data emphasizes the long-term effects the virus can have on the body.
>Skin problems are just one of the challenges faced by COVID-19 “long haulers,” who seem unable to fully recover from the virus.
>Redness and swelling of the hands and feet – popularly referred to as “COVID toes,” typically lasted about 15 days, but researchers found that six long haulers had toe symptoms lasting more than 60 days. Two confirmed coronavirus patients had COVID toes for over 130 days, according to the study.
>“Our findings reveal a previously unreported subset of patients with long-standing skin symptoms from COVID-19, in particular those with COVID toes. This data adds to our knowledge about the long-term effects of COVID-19 in different organ systems,” said study author Dr. Esther E. Freeman, director of Global Health Dermatology at MGH. “The skin is potentially a visible window into inflammation that could be going on in the body.”
https://archive.vn/wzSne
>SARS-2 heart changes raise death risk; virus may be lead killer of young adults during surges
https://archive.vn/vPAS2
>It’s now known that SARS-CoV-2 will leave a portion of the more than 23 million people it’s infected with a litany of physical, cognitive and psychological impairments, like scarred lungs, post-viral fatigue and chronic heart damage. What’s still emerging is the extent to which the enduring disability will weigh on health systems and the labor force. That burden may continue the pandemic’s economic legacy for generations, adding to its unprecedented global cost -- predicted by Australian National University scholars to reach as much $35.3 trillion through 2025 as countries try to stop the virus’s spread.
Global macroeconomic scenarios of the COVID-19
https://cama.crawford.anu.edu.au/sites/default/files/publication/cama_crawford_anu_edu_au/2020-06/62_2020_mckibbin_fernando_0.pdf
What it's like to be a SARS-2 'long-hauler' with symptoms that last for months
>A big challenge long-haulers face may be sustaining employment. Ultimately, it is too early to classify long-haulers as having a disability. Anthony Fauci reported that “it will take months to a year or more to know whether lingering COVID-19 symptoms in young people could be chronic illnesses.”
>Economics is a big driver of health, and the link between employment and health care in America further exacerbates the need to maintain employment to protect health. Employers need to be ready to make accommodations to keep long-haulers working. The stress of being sick long-term, combined with the possibility of job loss, can also contribute to mental health issues.
https://archive.vn/r8ZyJ
[]
Notably the WHO and Cornell group documented it and “they calculated risk of reinfection:
>reinfection risk estimated at 0.01% (95% CI: 0.01-0.02%)
>incidence rate of reinfection was estimated at 0.36 (95% CI: 0.28-0.47) per 10,000 person-weeks.”
An incidence rate of reinfection of 0.36 per 10k person-weeks equals:
>reinfection per 30k person weeks
>1 reinfection per 1000 recovered patients followed for 30 weeks.
>1 reinfection per 10k recovered patients followed for 3 weeks
For a case to be officially reported as reinfection, the current standard requires obtaining distinct genomic sequences of the virus for the first and second infections.
>But genomic sequencing is expensive and therefore is not usually conducted for viral samples.
>The percentage of people who have been confirmed as infected is still very low, e.g., about 8M/330M = 2.4% in the US.
>Assuming independence of the two instances of infection, the probability that someone in the US has been infected twice is 0.024 × 0.024 = 0.00058.
>Many patients did not even get a PCR test during the initial wave. So, we have missed many cases between January 2020 and May 2020.
>If the infecting viral load is not too high, many reinfections tend to be milder since the acquired immune response from a first infection seems to last for a few months.
>So, many reinfections are either not detected b/c asymptomatic, or not reported & tested b/c mild.
https://archive.vn/1K9f4
[]
SARS-CoV-2 hinders the innate and adaptive immune responses via dopamine-mediated disruption of intracellular biosynthesis
https://www.sciencedirect.com/science/article/pii/S165836122030158X
SARS-CoV-2 may induce long-term autoimmune disorder due to self-glycan antibody production
https://www.azolifesciences.com/news/20201020/SARS-CoV-2-may-induce-long-term-autoimmune-disorder-due-to-self-glycan-antibody-production.aspx
>The hypothalamus: target and culprit of immune dysregulation: The brain, the hypothalamus in particular, could also contribute to the immune dysregulation
>>In conclusion, the neurological manifestations of COVID-19 constitute a major public health challenge not only for the acute effects on the brain, but also for the long-term harm to brain health that may ensue. These delayed manifestations are anticipated to be significant since they are likely to also affect patients who did not show neurological symptoms in the acute phase.
https://www.sciencedirect.com/science/article/pii/S0092867420310709
Feinstein Institutes researchers find effective COVID-19 ‘cytokine storm’ treatment
>Some immune systems have responded to coronavirus disease 2019 (COVID-19) infections by going into overdrive, resulting in an overzealous inflammatory response referred to as a cytokine storm. In a retrospective study of nearly 6,000 patients, researchers from The Feinstein Institutes for Medical Research and Northwell COVID-19 Research Consortium have identified the most effective immunomodulatory therapies to treat patients with evidence of this cytokine storm and improve patient survival.
>The results show that the most effective treatment was the combination of corticosteroids – such as dexamethasone – with tocilizumab when compared to standard of care. Additionally, there was an improvement if corticosteroids were used alone, or in combination with tocilizumab or anakinra when compared with standard of care.
https://archive.vn/geVaS
FDA Approves First Ebola Treatment: What to Know
>The Food and Drug Administration approved a new treatment for Ebola virus disease, which could help control ongoing and new outbreaks.
>The treatment is called Inmazeb and made by Regeneron Pharmaceuticals.
>It’s a combination of three monoclonal antibodies.
>The monoclonal antibodies included in Inmazeb target a glycoprotein on the surface of the Ebola virus.
>The virus uses this glycoprotein to attach to human cells and fuse its own membrane with that of the host cell. This allows the virus to enter the cell and cause an infection.
>By binding to the glycoprotein, the three antibodies can block the virus from attaching to and entering the host cell.
>Leah Lipsich, PhD, who heads Regeneron’s global program for infectious diseases, told the Associated Press that using three monoclonal antibodies reduces the risk that the virus will become resistant to the drug.
>The drug, which is given as a single intravenous dose, was tested alongside three other drugs in a randomized, controlled trial conducted during a 2018-19 Ebola outbreak in the Democratic Republic of Congo (DRC).
>Of 155 people given Inmazeb, 33.5 percent died after 28 days, compared with 51.3 percent of 154 people who received another experimental triple monoclonal antibody drug.
>The most common symptoms experienced by those who received Inmazeb included fever, chills, fast heart rate, fast breathing, and vomiting. These are also common symptoms of an Ebola infection.
>Another group of participants received a single monoclonal antibody derived from an Ebola survivor. Of 174 people who received this drug, 35.1 percent survived after 28 days.
>A fourth group of participants received Gilead Sciences’ broad-spectrum antiviral remdesivir. About half of them died from Ebola.
https://web.archive.org/web/20201020225428/https://www.healthline.com/health-news/fda-approves-first-ebola-treatment-what-to-know
>Covid-19 patients FIVE TIMES more likely to die in hospital than those with flu, are at higher risk for 17 complications – CDC
https://www.rt.com/usa/504078-coronavirus-deadly-flu-cdc/
>a series of large online questionnaires focusing on COVID-19 recovery found that less than one percent of surveyed patients were symptom-free 79 days after the infection – which suggests the high likelihood of PCNS in over 90 per cent infected people.
https://pursuit.unimelb.edu.au/articles/what-is-post-covid-19-neurological-syndrome
AstraZeneca SARS-2 vaccine trial volunteer has died, Brazil health authority says
>Brazilian health authority Anvisa said on Wednesday that a volunteer in a clinical trial of the COVID-19 vaccine developed by AstraZeneca AZN.L and Oxford University has died, stating it had received data from an investigation into the matter.
>The regulator said testing of the vaccine would continue after the volunteer’s death. It provided no further details, citing medical confidentiality of those involved in trials.
>The Federal University of Sao Paulo, which is helping coordinate phase 3 clinical trials in Brazil, separately said that the volunteer was Brazilian but did not say where the person lived.
>AstraZeneca shares turned negative and were down 1.7%.
>The federal government already has plans to purchase the UK vaccine and produce it at its biomedical research center FioCruz in Rio de Janeiro, while a competing vaccine from China's Sinovac SVA.O is being tested by Sao Paulo state's research center Butantan Institute.
>Brazil has the second deadliest outbreak of coronavirus, with more than 154,000 killed by COVID-19, following only the United States. It is the third worst outbreak in terms of cases, with more than 5.2 million infected, after the United States and India.
https://archive.vn/UyfKD
Cognitive deficits in people who have recovered from SARS-2 relative to controls: An N=84,285 online study
>People who had recovered, including those no longer reporting symptoms, exhibited significant cognitive deficits when controlling for age, gender, education level, income, racial-ethnic group and pre-existing medical disorders. They were of substantial effect size for people who had been hospitalised, but also for mild but biologically confirmed cases who reported no breathing difficulty. Finer grained analyses of performance support the hypothesis that COVID-19 has a multi-system impact on human cognition
https://www.medrxiv.org/content/10.1101/2020.10.20.20215863v1
https://www.medrxiv.org/content/10.1101/2020.10.20.20215863v1.full.pdf
https://yaledailynews.com/blog/2020/10/22/ynhh-opens-neurocovid-clinic-to-treat-long-term-neurological-symptoms-associated-with-covid-19/
>YNHH opens neuroCOVID clinic to treat long-term neurological symptoms associated with COVID-19
[]
SARS-2 fucks with ferritin
http://archive.is/YKpLD
ferroptosis triggered by SARS-2:
https://www.researchgate.net/publication/341055648_COVID-19_iron_ferroptosis_parafibrin
Case report: Fatal lymphocytic cardiac damage in SARS-2: autopsy reveals a ferroptosis signature
https://archive.vn/prYO1
[]
> Excessive G–U transversions in novel allele variants in SARS-CoV-2 genomes
https://peerj.com/articles/9648.pdf
Trondheim strain
https://www.nrk.no/trondelag/ny-koronavariant-oppdaget-i-trondheim-1.15206064
the attack may still be ongoing
https://www.sbs.com.au/news/health-officials-investigate-mystery-coronavirus-strain-on-cargo-ship-off-queensland-coast
https://www.biorxiv.org/content/10.1101/2020.09.28.317685v1
>SARS-CoV-2 D614G Variant Exhibits Enhanced Replication ex vivo and Earlier Transmission in vivo
https://www.thailandmedical.news/news/v483g-mutation-warning-about-growing-prevalence-of-new-sars-cov-2-mutant-strain-v483g-that-is-antibody-resistant-and-even-more-infectious
>Antibody resistant AND more infectious.
>>>D614G strain with a I472V mutation on it that is also fast growing in the US and Europe. Not only antibody resistant but also more infectious, and there are are now studies underway that might indicate that it's also T-cell resistant
https://www.thailandmedical.news/news/breaking-covid-19-news-mutated-sars-cov-2-strain-d839y-n-e-with-super-antigens-inserts-identified-as-cause-of-multi-inflammatory-syndrome-mis-c-and-mi
>mutilates T-cells
https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31174-8
>SARS-CoV-2 ORF3b Is a Potent Interferon Antagonist Whose Activity Is Increased by a Naturally Occurring Elongation Variant
>Deletion polymorphism in intron 16 of the angiotensin I-converting enzyme(ACE) gene has been found to be associated with a risk of essential hypertension in some black American populations. Among some caucasian populations, however, this same polymorphism has been found to be associated with an increased risk for myocardial infarction. In an on-going family study in black Americans, we compared the frequency of the ACE deletion polymorphism in 21 hypertensive probands with 28 normotensive healthy controls drawn from the same clinic. The frequency of the deletion allele in hypertensive probands was significantly higher than in normotensive controls, 0.738 versus 0.571 with p<0.01. This suggests that polymorphism in or near the ACE gene might contribute to an increased risk of essential hypertension in blacks
https://archive.vn/ZXS3P
Preventing SARS-2: UCHealth Asking People Exposed To Virus To Try Regeneron Antibody Treatment
https://archive.vn/PJDez
>Remdesivir, now called Veklury, is the first coronavirus treatment to receive full approval from the Food and Drug Administration.
https://archive.vn/gs9AO
Stay-at-home orders reduced SARS-2 cases, deaths, study finds
>a modeling analysis using data from 131 countries published Thursday by The Lancet Infectious Diseases found the "least comprehensive" measures -- bans on public events and gatherings of more than 10 people -- cut disease transmission by nearly 30%, while more comprehensive, full-lockdown approaches led to a 52% reduction
https://archive.vn/qxRe3
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2772155
US: A vaccine isn’t expected to be authorized until late November or December — and there won’t be sufficient quantities for a release to the general public until at least the middle of 2021
https://www.mercurynews.com/2020/10/16/california-readies-its-covid-19-vaccine-distribution-plan/
[Peru] Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized SARS-2 patients:
>Among 5683 patients eligible for analysis, 200 received hydroxychloroquine or chloroquine within 48 hours of hospital admission, 203 received ivermectin, 1600 received azithromycin, 692 received hydroxychloroquine or chloroquine plus azithromycin, 358 received ivermectin plus azithromycin and 2630 received standard of care.
> AZIT + HCQ group was associated with 84% higher all-cause mortality hazard rate compared to standard care (wHR = 1.84, 95% CI: 1.12-3.02). Consistently, AZIT + HCQ treatment was associated with survival without transfer to ICU (wHR = 1.49, 95% CI: 1.01-2.19) and survival without oxygen prescription (wHR = 1.70, 95% CI: 1.07-2.69). HCQ treatment was associated with 77% higher all-cause mortality or oxygen prescription hazard rate compared to standard treatment (wHR = 1.77, 95% CI: 1.01-3.11).
>Surprisingly, we observed that IVM treatment was associated with less survival rate without transfer to ICU in the weighted analysis (wHR = 1.58, 95% CI:1.11-2.25) By last, we did not find evidence of effect on reduce all-cause mortality or increase survival rate without transfer to ICU or survival rate without oxygen prescription for AZIT group neither AZIT + IVM group in all analyses.
>The results of our target trial emulation match with previous findings of randomized clinical trials and observational studies, which showed no beneficial effects of hydroxychloroquine, ivermectin, azithromycin, or their combinations.
https://www.medrxiv.org/content/10.1101/2020.10.06.20208066v1
[Pre-print] SARS-CoV-2 mutations rundown and their effect on the severity of SARS-2 disease
>The researchers found 141 mutations, which had a significant correlation with the clinical outcome.
>Mutations related to mild disease
>Looking only at mutations observed in 2% or more of the samples, they found 64 samples correlated to 6 mutations in the ORF8, ORF3a, nsp4, nsp6, and the L and N proteins.
>Mutations associated with severe disease
>In samples from patients with moderate to severe disease, they found 9 mutations related to seven genes, including the D614G and L54F in the spike protein, one in the RdRp, and others in other structural and non-structural proteins.
>They also explored all mutations that were present in 10 or more severely ill patients. This showed two more mutations in the spike protein and the nsp7 gene, present in 28 and 11 severely ill patients.
>Overall, the prevalence of mutations correlated with a mild outcome was lower than with severe outcomes, at ~1,500 vs. 6,700 mutations. There were over 5,000 mutations that were not linked to any clinical outcome.
https://archive.vn/IR1UM
>Systematic review of EEG findings in 617 patients diagnosed with COVID-19
https://www.seizure-journal.com/article/S1059-1311(20)30332-0/fulltext
Singapore's first SARS-2 T cell trial to include severe cases
>Singapore's first Covid-19 specific T cell clinical trial is ready to recruit its first patients.Conducted by a research team from KK Women's and Children's Hospital (KKH), this human trial of a potential coronavirus treatment received approval from the Health Sciences Authority in July.
>The trial is targeting patients with severe Covid-19 disease as well as those at risk of developing severe disease.
>There are five hospitals where patients can receive this T cell treatment.Patients who develop severe Covid-19 disease were found to have low levels of T cells
>For this study, Covid-19 specific T cells were harvested from blood donated by six recovered Covid-19 patients.Around 350ml to 450ml of blood was collected from the first batch of donors in April.
>The T cells harvested from this blood, sufficient to treat 40 patients, are currently stored in a cell bank.
>Patients with severe Covid-19 will be treated with the T cells intravenously. Infected patients at risk of developing severe disease - such as those above the age of 65, or obese individuals - will be treated pre-emptively.
>The two main objectives of the trial are to prove that the T cells are safe to use, and that this treatment method is effective.
>For instance, to measure the efficacy of this trial, the clinical response in terms of time taken to recover from a Covid-19 infection would be measured.Patients will also be monitored for six months to a year to look out for side effects and to ensure that the trial is safe.
https://archive.vn/bSdGl
>"Compared to its older relative, the new coronavirus had acquired an 'extra piece' on its surface proteins, which is also found in the spikes of many devastating human viruses, including Ebola, HIV, and highly pathogenic strains of avian influenza, among others," says Olli Vapalahti, also a virologist from the University of Helsinki.
https://www.sciencealert.com/a-second-key-used-by-sars-cov-2-to-enter-cells-could-explain-why-it-s-so-infectiouse
Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study
> Comparing the ∆382-variant only group with the wild-type only group, those infected with the ∆382 variant were younger overall, with only one (3%) patient aged 65 years or older, in contrast to ten (11%) in the wild-type only group
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31757-8/fulltext
Study shows how exercise stalls cancer growth through the immune system
>Physical activity changes the metabolism of the immune system's cytotoxic T cells and thereby improves their ability to attack cancer cells. The study is published in the journal eLife.
>researchers divided mice with cancer into two groups and let one group exercise regularly in a spinning wheel while the other remained inactive. The result showed that cancer growth slowed and mortality decreased in the trained animals compared with the untrained.
>Next, the researchers examined the importance of cytotoxic T cells by injecting antibodies that remove these T cells in both trained and untrained mice. The antibodies knocked out the positive effect of exercise on both cancer growth and survival, which according to the researchers demonstrates the significance of these T cells for exercise-induced suppression of cancer.
>The researchers also transferred cytotoxic T cells from trained to untrained mice with tumors, which improved their prospects compared with those who got cells from untrained animals.
>To examine how exercise influenced cancer growth, the researchers isolated T cells, blood and tissue samples after a training sessions and measured levels of common metabolites that are produced in muscle and excreted into plasma at high levels during exertion. Some of these metabolites, such as lactate, altered the metabolism of the T cells and increased their activity. T cells isolated from an exercised animal showed an altered metabolism compared to T cells from resting animals.
>researchers examined how these metabolites change in response to exercise in humans. They took blood samples from eight healthy men after 30 minutes of intense cycling and noticed that the same training-induced metabolites were released in humans.
https://archive.vn/QEnT4
>Coronavirus can knock eight points off your IQ: Virus causes 'brain fog' that can cause mental damage similar to the mind aging a decade, research suggests
>Some survivors even recorded the equivalent of an 8.5-point drop in their IQ
COVID Can Age the Brain by a Decade, Study Suggests
>COVID-19 may cause some people's brains to age by around 10 years when compared with those who have not had the disease,
>Participants who said they had COVID-19 performed worse on cognitive tests than those from the control group.
>The link was particularly strong for those with severe COVID-19, but was also apparent in those had a mild form of the disease.
>A mild COVID-19 case was defined in the study as someone who did not have breathing problems.
>Patients aged 20 to 70 years old who were hospitalized and put on a ventilator to help with their breathing saw their thinking skills decline to the level of a person 10 years their senior, on average. brains of some with COVID-19 aged approximately 10 years compared to those without the disease "is much worse" than what is seen in other people who have recovered from other viruses.
https://www.newsweek.com/covid-age-brain-decade-study-1542374
>Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants
https://elifesciences.org/articles/61312
The compelling link between physical activity and the body's defense system
>Acute exercise is an immune system adjuvant that improves defense activity and metabolic health.
>Data support a clear inverse relationship between moderate exercise training and illness risk.
>Exercise training has an anti-inflammatory influence mediated through multiple pathways.
>Illness risk is increased in athletes during periods of intensified training and competition.
>Increased carbohydrate and polyphenol intake is an effective nutritional strategy for immune support.
>Habitual exercise improves immune regulation, delaying the onset of age-related dysfunction.
https://archive.vn/jVhFl
https://time.com/5903423/plasma-coronavirus-risk-of-dying/
Researchers in India report that COVID-19 patients who received convalescent plasma from recovered patients did not see a lower risk of dying from the disease.
“This study had a large sample size and it showed that when plasma is infused in patients who have moderate COVID-19 (similar to severe in other countries), it did not reduce mortality or progression to more critical COVID-19,”
https://www.the-scientist.com/news-opinion/sars-cov-2-disables-key-components-of-human-cells-defense-system-68073
. To the team’s surprise, Guttman says, as many as four proteins bound specifically to structural noncoding RNAs that make up the cell machinery in charge of coordinating those processes.
We want to understand how the virus can disrupt host cell machinery and yet be able to engage ribosomes, be able to engage the trafficking machinery—all these things that have been shut off.
team predicted that infection with SARS-CoV-2 would drastically reduce splicing, translation, and protein transport in human cells and would consequently suppress the interferon response, which relies on boosting these three processes. Indeed, lung epithelial cells infected with the virus showed just that, the researchers report.
“What are the signals being presented by the viral mRNAs to basically give it a ticket to ride on all of those machines?”
Preliminary data indicate that distinctive loops in the structure of SARS-CoV-2 mRNAs could be acting as those signals,
Some SARS2 Survivors Have Antibodies That Attack the Body, not Virus
>Some survivors of SARS2 carry worrying signs that their immune system has turned on the body, reminiscent of potentially debilitating diseases like lupus and rheumatoid arthritis, a new study has found.
>At some point, the body’s defense system in these patients shifted into attacking itself, rather than the virus, the study suggests. The patients are producing molecules called “autoantibodies” that target genetic material from human cells, instead of from the virus.
>This misguided immune response may exacerbate severe SARS2. It may also explain why so-called “long haulers” have lingering problems months after their initial illness has resolved and the virus is gone from their bodies.
>The findings carry important implications for treatment: Using existing tests that can detect autoantibodies, doctors could identify patients who might benefit from treatments used for lupus and rheumatoid arthritis. There is no cure for these diseases, but some treatments decrease the frequency and severity of flare-ups.
>“You never really cure lupus — they have flares, and they get better and they have flares again,” she said. “And that may have something to do with autoantibody memory.”
>Dr. Marshak-Rothstein, Dr. Iwasaki and dozens of other teams are closely studying the immune response to SARS2. Given the ease of testing for autoantibodies, it may soon become clear whether the antibodies were identified only because the researchers went looking for them, or whether they represent a more permanent alteration of the immune system.
>“It’s not clear to me what it all means at this point,” Dr. Pepper said. “It’s going to take a little bit of time to understand if this is something that’s going to lead to downstream pathology.”
https://archive.is/SUX5V
To study virus transmission, Herfst and his colleagues stacked two ferret containers on top of one another, connected only by a 15 cm–wide duct made of PVC pipe with four 90-degree turns. They infected each of three groups of four ferrets, called “donor ferrets,” with a different virus. One set received SARS-CoV-2; another group got SARS-CoV, the virus responsible for the 2003 SARS outbreak; and a third was infected with H1N1 influenza, the virus behind the 2009 flu pandemic, as a positive control. “The proof for airborne transmission in humans is super limited, and you can’t do those experiments in humans for obvious reasons,”
researchers placed each donor ferret by itself in the bottom of the two-cage apparatus and a single healthy ferret, called the “indirect recipient ferret,” in the top cage, with a steel grate closing both ends of the duct to trap any food, feces, or other large particles. A fan carried air from the bottom cage to the top cage at 100 liters per minute.
The researchers swabbed the ferrets’ noses and throats every other day to measure the amounts of viral RNA and infectious virus present. By the end of the 13-day experiment, all indirect recipient ferrets in the influenza and SARS-CoV groups had caught the viruses from the donor ferrets, while two of the four SARS-CoV-2 recipients were infected. The four donor and four recipient ferrets infected with SARS-CoV became seriously ill, exhibiting breathing difficulties and less activity than usual, while those infected with SARS-CoV-2 were fully asymptomatic.found that the virus transmits effectively through the air, he says he hopes to next tackle how long infectious virus can be detected in the air around infected ferrets, which would help answer how long individuals remain contagious
https://medicalxpress.com/news/2020-10-percent-patients-recovered-covid-virus.html
Close to 17 percent of patients recovered from COVID-19 could still carry virus. close to 17 percent of patients considered fully recovered from COVID-19 tested positive for the virus in follow-up screening. Patients who continued to have respiratory symptoms, especially sore throat and rhinitis, were more likely to have a new positive test result. This suggests the persistence of these two symptoms should not be underestimated and should be adequately assessed in all patients considered recovered from COVID-19.
Twenty-two (16.7 percent) of the patients tested positive again. Theree was no significant difference between patients with positive and negative test results in terms of age or sex.findings indicate that a noteworthy rate of recovered patients with COVID-19 could still be asymptomatic carriers of the virus.
"The main question for the containment of SARS-CoV-2 pandemic infection that still needs to be answered is whether persistent presence of virus fragments means the patients is still contagious. The RT-PCR test looks for small fragments of viral RNA. A positive swab test can reveal if patients are still shedding viral fragments, but it is not able to discern whether they are or aren't infectious."
>we observe a consistent and rapid growth of this variant in multiple countries and its frequency is above 50% in some localities.
>Its frequency in the UK has continued to increase even after quarantine-free travel was discontinued and the main summer travel period ended.
>Thus this variant might transmit faster than competing variants.
>Notably, case numbers across Europe started to rise rapidly around the same time the 20A.EU1 variant started to dominate in Spain, Switzerland and the UK (limited sequence data are available for other countries and we can not draw clear conclusions), see Fig. S2.
>However, this acceleration of transmission also coincided with the arrival of fall and seasonal factors are an alternative or compounding explanation.
https://www.medrxiv.org/content/10.1101/2020.10.25.20219063v1
https://medicalxpress.com/news/2020-10-sars-cov-variant-europe-summer.html
[chink pre-print] Furin cleavage site and D614G on SARS-CoV-2 spike evolved to balance infectivity, stability, cytopathicity
>For this study, they looked at the S gp expression on the genetic makeup of the virus and the "association, glycosylation, and incorporation" of these sequences onto lentivirus and vesicular stomatitis virus (VSV) and other SARS-CoV-2 virus-like particles (VLPs).
>this furin cleavage site of the SARS-CoV-2 S glycoprotein reduced the virus stability and infectivity but raised its ability to form lethal syncytia. They noted that the D614G change seen in the present strains of SARS-CoV-2 restores its infectivity and enhances its affinity towards the ACE2 receptor and susceptibility to an antibody-containing serum. The D614G change also strengthens the association of the S1 subunit with the trimer.
>The team writes, "Apparently, two unique features of the SARS-CoV-2 S glycoprotein, the furin cleavage site, and D614G, have evolved to balance virus infectivity, stability, cytopathicity, and antibody vulnerability."
>They also noted that the endodomain (cytoplasmic tail) of the S2 subunit decreased the virus entry or syncytium formation. They also found that the protease inhibitors prevent proteases from breaking the S gp and suppress the S glycoprotein function. Matrix metalloprotease inhibitors also decrease the S-mediated cell-cell fusion but do not affect the cell's virus entry
>Synergy between inhibitors of matrix metalloproteases and TMPRSS2 suggest that both proteases can activate the S glycoprotein during the process of syncytium formation
https://archive.vn/9ZpHA
APS technique shows how SARS-CoV-2 virus camouflages itself inside the human body
>SARS-CoV-2 virus uses some unique ways to camouflage its messenger ribonucleic acid (RNA), the single-stranded molecule that carries the genetic code for synthesizing proteins, to mimic those of the host cell. The immune system cannot differentiate it from the body's own messenger RNA, so it doesn't fight the virus off.
>It is a little like wearing a blue-collared shirt for Best Buy. You may not work there, but people will treat you like you do, in the same way, that a host cell's immune system will treat the virus-like it belongs.
>"The virus uses the classical mechanism of camouflaging and exploiting the host machinery for its own protein synthesis," he said. "It goes inside the host cell and its messenger RNA looks the same as the host messenger RNA."
>Gupta said this process was thought to be similar to those seen in previous coronaviruses, but his team observed some unique features in the SARS-CoV-2 protein. Understanding how this particular virus uses this protein to avoid detection will help with designing new treatments. What's needed, he said, is a drug that targets the virus, not the host, and knowing more about the camouflage mechanism will help develop one.
https://archive.vn/hFKr3
https://archive.vn/dca0C
New drug candidate for the treatment of SARS-2
>approved protease inhibitor aprotinin displayed activity against SARS-CoV-2, the coronavirus that causes COVID-19, in concentrations that are achieved in patients. Aprotinin inhibits the entry of SARS-CoV-2 into host cells and may compensate for the loss of host cell protease inhibitors that are downregulated upon SARS-CoV-2 infection.
>Aprotinin aerosols are approved in Russia for the treatment of influenza and could be readily tested for the treatment of COVID-19.
>Professor Martin Michaelis said: 'The aprotinin aerosol has been reported to be tolerated extremely well in influenza patients. Hence, it may have a particular potential to prevent severe COVID-19 disease when applied early after diagnosis.'
https://archive.vn/wxCFa
Symptoms and outcomes of 3.32 million people tested for SARS-CoV-2
>Most of the participants were adults below 64 years, with 20% to 48% being over 65, depending on the study. The proportion of women varied from 52% to 64% in almost every study included. The positives usually had a higher prevalence of chronic illness, specifically heart disease and hypertension, at ~42% and ~60% in the positive group vs. 19% and ~20% in the tested group. Obesity was also more common among the positives, at ~44%, versus 31% in the tested group.
>Earlier studies have also shown that hypertension, heart disease, and diabetes are more common among those with COVID-19.
>Symptoms most commonly reported in the tested group were cough, fever, and shortness of breath. Their prevalence was still higher in the positives, and patients hospitalized for any cause.
>At 30 days from diagnosis, ~4% to ~38% of positives had been hospitalized in various studies. The proportion of deaths in this period ranged from ~9% to ~11%. Outcomes tended to improve over time.
>The 45% rate of hospitalization in March 2020 declined to ~14% by May, and the 30-day death rate from 11% to ~1% in the same period. Positives with pneumonia in this period made up ~4% to ~22% of the whole, while 1% to 12% developed acute respiratory distress syndrome (ARDS).This agrees with other reports, such as those from the US Centers for Disease Control and Prevention (CDC).
>Patients who tested positive for COVID-19 had a risk of sepsis ranging from 0.6% to ~5%. In this group, the most frequently occurring kidney complication was acute kidney injury, at up to ~8%, with dialysis being required in 1.5%.
>When the total composite cardiovascular event outcome is considered, 0.2% to 5% of these patients were affected. Venous thromboembolism (VTE) was observed in 0.2% to ~2%.
https://archive.vn/BHoMr
https://archive.vn/YDW1H
[Pre-print] Researchers in the UK have conducted a study showing that a high proportion of patients admitted to intensive care units (ICU) with SARS-2 acquire a secondary bacterial co-infection during their hospital stay.
>The retrospective cohort study of patients admitted to seven ICUs in England up to May 18th, 2020 found that the longer the ICU stay, the more significant the proportion of patients who developed nosocomial (hospital-acquired) infections.
>While bacterial co-infection within 48 hours of ICU admission was uncommon, the proportion of pathogens detected started to increase after 48 hours. The pathogens mostly consisted of Gram-negative bacteria, particularly Klebsiella pneumoniae and Escherichia coli.
>Patients who developed these infections were significantly more likely to die in ICU than those without co-infections.
>“This pragmatic multicenter study provides novel data on both community-acquired and nosocomial co-infection in patients with COVID-19 requiring ICU care in England," writes Vadsala Baskaran Nottingham University Hospital NHS Trust and colleagues.
>The researchers say the finding that co-infection among COVID-19 patients is uncommon early on during hospitalization supports the recommendations that empirical antibiotics should not be used at the point of admission unless a bacterial infection is suspected.
>It is possible that reducing unnecessary exposure to such antibiotics could lower the risk of patients later acquiring Gram-negative infections that are potentially resistant to antibiotics, they add.
>Gram-positive bacteria are more susceptible to treatment with antibiotics than Gram-negative bacteria since they have a single-layered cell wall that is more easily penetrated than the double-layered cell wall of Gram-negative bacteria.
https://archive.vn/jAkhL
https://www.medrxiv.org/content/10.1101/2020.10.27.20219097v1
Plasma irradiation efficiently inactivates the coronaviruses
>Treatment of SARS-CoV-2 in culture medium with a plasma discharge resulted in 95.17% viral inactivation after plasma irradiation after 1 hour, 99.54% inactivation after 2 hrs and 99.93% inactivation after 3 hrs
https://www.biorxiv.org/content/10.1101/2020.11.13.381319v1
https://www.biorxiv.org/content/10.1101/2020.11.13.381319v1.full.pdf
Nanobodies: unharnessed potential in SARS-2 treatment
>The current study deals with the quest to develop nanobodies (Nbs) or VHHs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which are a novel class of proteins based on antibody fragments with only one domain. They are derived from the heavy chain variable domains of camelids such as camels, llamas and alpacas, lacking a light chain component.
>The Nb domains have full antigen-binding potential, with high affinity for their antigens. These have the smallest intact antigen-binding domain (about 15 kDa) and are only about 110 residues in length.
>Nb domains have immense potential as therapeutic proteins for several reasons: their small size, stability, high solubility, cost-effective production in a yeast vector and high tissue penetration due to their low molecular weight. However, at present, they cannot be administered systemically because of low gut absorption.
Antiviral advantages of Nbs
>Nbs have been explored as antiviral agents in many respiratory illnesses, such as Middle East respiratory syndrome (MERS), influenza type A, and respiratory syncytial virus infections. Recently, a pair of VHHs from a llama immunized with the stabilized prefusion form of the receptor-binding domain (RBD) of the coronavirus spike protein was found to neutralize both MERS and SARS coronaviruses. The VHH directed against the spike RBD bound to the spike with high affinity.
>Three other VHHs have been found which bind to the RBD of SARS-CoV-2 and inhibit the RBD-ACE2 interaction that is essential for viral entry into the host cell, a finding which is important in view of the current pandemic.
>Several researchers have reported the anti-inflammatory capabilities of Nbs too, which could help reduce cytokine production and the risk of a cytokine storm
Diagnostic applications
>Nbs are also potentially useful for diagnostic applications.
https://archive.vn/PzifQ
>melatonin usage is significantly associated with a 28% reduced likelihood of a positive laboratory test result for SARS-CoV-2 confirmed by reverse transcription–polymerase chain reaction assay. Using a PS matching user active comparator design, we determined that melatonin usage was associated with a reduced likelihood of SARS-CoV-2 positive test result compared to use of angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (OR = 0.69, 95% CI 0.52–0.90). Importantly, melatonin usage (OR = 0.48, 95% CI 0.31–0.75) is associated with a 52% reduced likelihood of a positive laboratory test result for SARS-CoV-2 in African Americans after adjusting for age, sex, race, smoking history, and various disease comorbidities using PS matching. In summary, this study presents an integrative network medicine platform for predicting disease manifestations associated with COVID-19 and identifying melatonin for potential prevention and treatment of COVID-19
https://archive.vn/WFGGi
Diabetes raises SARS-2 mortality by 7 percent
https://archive.vn/iwtJZ
Uncaria tomentosa – a woody vine native to South America known of as "Cat's claw" - hydroalcoholic extract inhibits replication of SARS-CoV-2 in vitro
https://archive.vn/3XF85
https://www.biorxiv.org/content/10.1101/2020.11.09.372201v1
Children hardest hit by Covid-19 are ‘regressing' back into nappies and forgetting how to use a knife and fork
>Youngsters have lapsed back into nappies and forgotten how to eat with a knife and fork, while older children now lack “stamina” in reading and writing due to the coronavirus pandemic, Ofsted has warned.
>A series of reports from the watchdog suggest that children hardest hit by nursery and school closures have regressed in some basic skills and learning.
>Some children have fallen behind with their mathematics and are struggling with literacy, while school leaders have reported a rise in older pupils self-harming or suffering from eating disorders, according to Ofsted.
>The report into the impact of the pandemic is based on more than 900 visits to education and social care providers across England since September.
>Inspectors found children’s experiences were not necessarily determined by privilege or deprivation. Rather, those children who are coping well have good support structures around them, the report found.
>The report found some pupils’ concentration, or their mental and physical stamina, had reduced during the pandemic, with headteachers reporting that students were finding it difficult to write for long periods of time.
>“Some leaders said pupils were fatigued, ‘disconnected’ from learning or struggling to stay awake and alert,” it adds.
https://archive.vn/EObjk
Synthetic Mini-Antibody Could Combat SARS-CoV-2
>synthetic mini-antibodies are based on a unique type of small antibody called nanobodies that can be found in the blood of Camelids, the family of animals that includes camels, llamas, alpacas, and vicuñas. Nanobodies are around one-tenth of the size of a conventional antibody found in other mammals and have proved to be a promising agent against viruses thanks to their size and versatility. Most interestingly, research from earlier this year also showed that nanobodies from a llama are capable of binding to SARS-CoV-2, halting the virus from invading a cell.
>Scientists don’t always have to drain these nanobodies straight out of the llama’s blood, with new technology allowing researchers to select synthetic nanobodies, called sybodies, with relative ease. In a new study, reported in Nature Communications, researchers from the European Molecular Biology Laboratory Hamburg in Germany sifted through a recently developed library of sybodies and attempted to pinpoint those that target the spike protein of SARS-CoV-2.
https://archive.vn/l0uMj
Genetic association analysis of SARS-CoV-2 infection in 455,838 UK Biobank participants
https://www.medrxiv.org/content/10.1101/2020.10.28.20221804v1
https://www.medrxiv.org/content/10.1101/2020.10.28.20221804v1.full.pdf
>delirium could be an early symptom of SARS-2
https://archive.vn/UXyf0
https://www.heraldopenaccess.us/openaccess/delirium-in-severe-acute-respiratory-syndrome-coronavirus-2-infection-a-point-of-view
Antiviral activity of plant juices and green tea against SARS-CoV-2 and influenza virus in vitro
>We found that black chokeberry (Aronia melanocarpa) juice, pomegranate (Punica granatum) juice, and green tea (Camellia sinensis) have virucidal activity against both viruses, suggesting that oral rinsing may reduce viral loads in the oral cavity thereby lowering virus transmission
https://www.biorxiv.org/content/10.1101/2020.10.30.360545v1
>dexamethasone, which is used to reduce inflammation in other diseases such as arthritis, reduced death rates by around a third among the most severely ill of COVID-19 patients admitted to hospital
https://archive.vn/uswWd
COVID Symptom Study app research highlights delirium as a key sign of COVID-19 in older people
>The study included 322 hospitalised patients admitted with COVID-19 and 535 users of the COVID Symptom Study app who reported having had a positive test result.
>Dr Claire Steves from King’s College London said: “Knowing that delirium is a symptom in frail, elderly people will help families and carers spot the signs earlier of COVID-19 and act appropriately and put in place infection control measures such as isolation, increased hygiene and personal protective equipment to protect this highly vulnerable group.”
>They found that older adults admitted to hospital who were classified as frail according to a standard scale were more likely to have had delirium as one of their symptoms than people of the same age who were not classed as frail. Delirium, along with tiredness and breathlessness, were also more common in frailer users of the COVID Symptom Study app with COVID-19, compared with fitter people of the same age.
>A third of app users experiencing delirium did not report suffering the ‘classic’ COVID-19 symptoms of cough and fever, while delirium was the only symptom for around one in five (18.9%) of hospitalised patients.
https://archive.vn/e3sl7
High Virus Concentrations Found In Stamford, Bridgeport Sewage
>A spike in COVID-19 infections may coincide with an increase in the virus being detected in sewage in Stamford and Bridgeport, according to Yale researchers.
>“Discouraging news from New Haven this morning. A sharp increase in the concentration of SARS-CoV-2 RNA concentration in the wastewater from metro New Haven," he wrote. "This has been shown to be a leading indicator of a spike in cases, hospitalizations, and deaths.”
>“A general rule of thumb is that a virus concentration value between 1,000 to 2,000 RNA copies per mL roughly equates to 1 new daily case per 100,000 population. For example, a virus RNA value of 6,000 genome copies per mL in New Haven’s facility, would roughly equate to 3 to 6 new cases/100K that day for the population (New Haven, Hamden, East Haven, part of Woodbridge) served by this treatment facility.”
https://news.yahoo.com/high-virus-concentrations-found-stamford-165538699.html
Pandemic to increase heating costs, natural gas use this winter
>Natural gas use is expected to rise this winter as more people stay at home because of the coronavirus pandemic.
>Residential natural gas consumption from October to March is forecast to average 21.1 billion cubic feet per day, a 5 percent increase compared with last winter, according to the Energy Information Administration.The forecast will be a boon to shale gas producers during the pandemic, which has depressed gas prices. The average retail price for residential natural gas this winter is expected to average $9.55 per thousand cubic feet, down 2 percent from last winter, according to the EIA.
>But the bump in natural gas use is expected to offset the lower gas prices
https://www.mrt.com/business/energy/article/Pandemic-to-increase-residential-consumption-of-15693639.php
Risk of Stroke in Hospitalized SARS-CoV-2 Patients: A Meta-Analysis
>The overall stroke risk in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is 0.5%. Independent predictors of stroke among this population are mechanical ventilation and history of ischemic heart disease, according to data from a multinational meta-analysis published in EBioMedicine.
>The meta-analysis included 17,799 hospitalized patients from 99 tertiary centers from 11 countries. Of the 156 patients (0.9%) who had a stroke, 123 patients (79%) presented with an ischemic stroke, 27 patients (17%) presented with an intracerebral or subarachnoid hemorrhage, and 6 patients (4%) presented with a cerebral sinus thrombosis. The median National Institutes of Health Stroke Scale (NIHSS) scores upon presentation for patients with an acute ischemic stroke and intracerebral or subarachnoid hemorrhage were 9.5 (range, 6.0-19.0) and 3.0 (2.0-4.0), respectively.
>According to the data, the risk of subsequent stroke in infected patients is 156/17,799 (non-weighted simple pooled analysis, 0.9%). The meta-analysis of data from 43 regions suggested an overall stroke risk to be 0.5%
https://archive.vn/vlWv5
>Regeneron halts trial of antibody treatment in seriously ill Covid patients
https://archive.vn/7LXqq
>Regeneron's antibody drug likely to be in short supply because it's grown in live cells
https://archive.vn/UOky0
Co-infections: testing macrolides for added benefit in patients with SARS-2
>for the management of co-infections, macrolide antibiotics are particularly useful. Although azithromycin is actively being pursued,1 we would also like to suggest josamycin as a worthwhile alternative. Both macrolides are indicated for the treatment of a variety of respiratory infections including pharyngolaryngitis, acute bronchitis, and pneumonia, and the minimum inhibitory concentration of these drugs for the treatment of these infections are rapidly reached in the lungs.2 With regards to COVID-19, macrolides are well known for their anti-inflammatory and immunomodulatory effects, observed in pulmonary inflammatory disorders such as diffuse panbronchiolitis, asthma, and cystic fibrosis.
>josamycin could be a good choice for patients with COVID-19, as these patients often develop fibrosis-related comorbidities and serious inflammatory symptoms
https://archive.vn/6xez7
>researchers found that T3, a thyroid hormone that the body produces, is absent in the lungs of patients who died of ARDS — respiratory distress that can prove fatal in COVID-19 and other illnesses.
>The doctors obtained approval to test the T3 therapy even before the novel coronavirus was discovered in China. They have administered the drug directly to the lungs of two severe COVID-19 patients, and both of them survived.
>The FDA has cleared the project for a Phase 2 study, aiming to prove the drug is effective in coronavirus-induced ARDS.
https://archive.vn/04nQD
>Autoimmune antibodies as the new cause of blood clots
https://www.thailandmedical.news/news/covid-19-latest-university-of-michigan-and-nih-study-identifies-autoimmune-antibodies-as-new-cause-of-covid-19-blood-clots
The wide spectrum of neuropsychiatric complications in SARS-2 patients within a multidisciplinary hospital context
>We conducted a retrospective, observational study on all patients showing neurological or psychiatric symptoms in the context of Covid-19 seen in the Department of Neurology and Psychiatry of the APHP-Sorbonne University. We collected demographic data, medical and treatment history, comorbidities, symptoms, date of onset, and severity of Covid-19 infection, neurological and psychiatric symptoms, neurological and psychiatric examination data and, when available, results from cerebrospinal fluid (CSF) analysis, brain magnetic resonance (MRI) imaging, 18-fluorodesoxyglucose-position emission computed tomography (FDG-PET/CT)), electroencephalography (EEG) and electroneuromyography (ENMG). Results: 245 patients were included in the analysis. One-hundred fourteen patients (47%) were admitted to the intensive care unit (ICU) and 10 (4%) died. The most frequently reported neuropsychiatric symptoms were motor deficit (41%), cognitive disturbance (35%), impaired consciousness (26%), psychiatric disturbance (24%), headache (20%) and behavioral disturbance (18%).
>The most frequent syndromes diagnosed were encephalopathy (43%), critical illness polyneuropathy and myopathy (26%), isolated psychiatric disturbance (18%), and cerebrovascular disorders (16%). No patients showed evidence of SARS-CoV-2 in their CSF. Encephalopathy was associated with greater age and higher risk of death. Critical illness neuromyopathy was associated with an extended stay in the ICU
https://archive.is/xjyXi
Modelling the Anatomical Distribution of Neurological Events in SARS-2 Patients: A Systematic Review
>We identified 35 articles consisting of 123 patients that assessed the spatial distribution of small neurological events among COVID-19 patients. Of these, 91 patients had grey matter changes, 95 patients had white matter changes and 72 patients had confirmed cerebral microbleeds. White matter events were observed within 14 of 42 white matter bundles from the IIT atlas. The highest proportions (26%) of events were observed within the bilateral corticospinal tracts. The splenium and middle of the corpus callosum were affected in 14% and 9% of the cases respectively. Grey matter events were spatially distributed in the 41 brain regions within the Desikan-Killiany atlas. The highest proportions (~10%) of the events were observed in areas including the bilateral superior temporal, precentral, and lateral occipital cortices. Sub-cortical events were most frequently identified in the Pallidum.
https://archive.vn/mAdL0
https://www.medrxiv.org/content/10.1101/2020.10.21.20215640v1.full.pdf
Regeneron paused dosing of garetosmab (REGN2477) in trial in patients with the ultra-rare genetic disorder fibrodysplasia ossificans progressiva (FOP). The decision was based on reports of _fatal serious adverse events_ in the trial during the open-label extension, during which all patients received active treatment.
https://archive.vn/kuVAa
> Prothrombotic antiphospholipid antibodies in SARS-2
> suggest that a significant percentage of patients with COVID-19 become at least transiently positive for aPL and that these aPL are potentially pathogenic
> While both anticoagulation and corticosteroids have shown some promise to date in treatment of COVID-19, plasmapheresis has not been systematically explored. One wonders if this could provide benefit in the subgroupof COVID-19 patients with high titers of aPL. At the same time, convalescent plasma is receiving increasing attention as an approach to treating severe cases of COVID-19.
> Defining the extent to which these samples may contain aPL or other autoantibodies, in addition to protective anti-SARS-CoV-2antibodies, is another potential area for future investigation
https://www.medrxiv.org/content/10.1101/2020.06.15.20131607v2
Ultrapotent SARS-2 Vaccine Designed via Computer: Innovative Nanoparticle Vaccine Spurs Extremely High Levels of Protective Antibodies
https://archive.vn/V4e7Q
https://www.cell.com/cell/pdf/S0092-8674(20)31450-1.pdf
>Trump Promised a Vaccine by Election Day—None Have Even Applied for Approval
https://archive.vn/WNPwk
>New-onset refractory status epilepticus (NORSE) in post SARS-CoV-2 autoimmune encephalitis: a case report
https://archive.is/TGZ46
Exposure to environmental immunotoxicants may worsen outcome of SARS-CoV-2 infection
https://web.archive.org/web/20201104172450/https://www.news-medical.net/news/20201102/Exposure-to-environmental-immunotoxicants-may-worsen-outcome-of-SARS-CoV-2-infection.aspx
Case study details leukemia patient who shed infectious SARS-CoV-2 for at least 70 days
>Researchers report November 4 in the journal Cell an unusual case of one woman with leukemia and a low antibody count who was infected with the coronavirus for at least 105 days, and infectious for at least 70, while remaining asymptomatic the entire time.
>"At the time we started this study, we really didn't know much about the duration of virus shedding," says senior author Vincent Munster, a virologist at the National Institute of Allergy and Infectious Diseases. "As this virus continues to spread, more people with a range of immunosuppressing disorders will become infected, and it's important to understand how SARS-CoV-2 behaves in these populations."
>Munster, an expert in emerging infectious diseases, began publishing research on SARS-CoV-2 in January. He was contacted in April by infectious disease specialist Francis Riedo, a study co-author, about a patient in Kirkland, Washington, who had been infected very early in the COVID-19 pandemic. Riedo's patient had had numerous positive PCR tests for the virus over a period of weeks, and he wanted to know if she was still shedding virus.
>The patient, a 71-year-old woman, was immunocompromised due to chronic lymphocytic leukemia and acquired hypogammaglobulinemia. She never showed any symptoms of COVID-19. She was found to be infected with the virus when she was screened after being admitted to the hospital for severe anemia and her doctors recognized that she had been a resident of a rehabilitation facility experiencing a large outbreak.
https://archive.vn/cQjSZ
>COVID-19 Paper of the month: Neurological manifestations in 404 COVID‑19 patients in Washington State
>The study reported 73.0% patients in total with neurological symptoms. Authors found that female and Asian patients were more likely to have neurological features of COVID-19 infection but these data did not reach statistical significance.
https://www.eanpages.org/2020/11/01/covid-19-paper-of-the-month-neurological-manifestations-in-404-covid‑19-patients-in-washington-state/
Long-term symptoms of COVID-19 ‘really concerning’, says WHO chief
https://news.un.org/en/story/2020/10/1076562
>The Latest Scientific Theories Around SARS-2 Brain Fog
>Jason studies chronic fatigue syndrome, which is also known as myalgic encephalomyelitis. He says that the symptoms and timelines of ME/CFS appear to closely resemble those associated with post-Covid syndrome.
>For a recent study published in the Journal of Infection, a group of doctors followed up with 120 former Covid-19 patients three months after hospital discharge. Roughly 1 in 3 said that memory loss was a persistent issue, and 28% said they still had problems concentrating.
>Another report, published in July by researchers at Indiana University, surveyed more than 1,500 people who’d had Covid-19 and were still experiencing health problems months later. Concentration and memory impairments were some of the most common symptoms among these Covid-19 “long-haulers.”
>Natalie Lambert, PhD, is author of that report and an associate research professor at the Indiana University School of Medicine. She has continued to collect data on long-haul symptoms, and is getting ready to publish a larger report based on 4,000 respondents. “More than half of the respondents said they have difficulty concentrating or focusing, and 39% said they have memory problems,” she says.
>according to an app-based survey of more than 4 million people — led by researchers at Massachusetts General Hospital, Harvard Medical School, and King’s College London — roughly 1 in 20 people who get Covid-19 still experience lingering symptoms, including brain fog, eight weeks after infection
https://elemental.medium.com/the-latest-scientific-theories-around-covid-19-brain-fog-6a7c76d7a060
Study on the merits of PET brain scans to detect and monitor coronachan and her symptoms:
>a large fraction of patients with severe COVID-19 presented with abnormal brain magnetic resonance imaging (MRI), and lesions compatible with brain encephalopathy
>Early PET findings detected FDG hypometabolism in multiple brain areas, including the bilateral gyrus rectus, prefrontal and orbitofrontal cortices, and cerebellar vermis, of COVID-19 patients.
>Alterations in oxygen metabolism were also found in the brain of COVID-19 patients [1]. In fact, SARS-CoV-2 is likely to induce oxygen dysmetabolism in neuronal cells. In this context, the PET radiotracer O2 may help us to examine the prevalence of hypoxia in the brain of COVID-19 patients.
>Based on the high density of hACE2 in glutamatergic neurons, it seems reasonable to hypothesize that excitotoxicity might be implicated in COVID-19 and possibly some of its neurological manifestations.
>The serotoninergic system might be a particularly intriguing target for research in the context of COVID-19, in part, due to its involvement in mood disorders and social cognition.
>Furthermore, inflammatory CNS syndromes, including encephalitis, acute disseminated encephalomyelitis, and myelitis have been found in COVID-19 patients. Neuroinflammatory changes can be assessed, for instance, using PK11195, a widely used radiotracer to track microglial activation, and DED, a radiotracer for detecting reactive astrogliosis.
https://doi.org/10.1016/j.tins.2020.10.010