Reports the identification and characterization of (nCoV-2019). Full-length genome sequences were obtained from patients, and were found to share 79.5% sequence identify to SARS-CoV, and to be 96% identical at the whole genome level to a bat coronavirus. Study confirmed that virus uses the same cell entry receptor, ACE2, as SARS-CoV.
Stochastic simulations of early outbreak trajectories revealed that transmission characteristics were similar in magnitude to SARS-CoV and the 1918 influenza pandemic. Findings underlie importance of surveillance and early control in controlling viral transmission.
Bronchoalveolar lavage was collected from 7 workers at the Wuhan seafood market. Next generation metagenomic RNA sequencing identified an RNA virus of family Coronaviridae, called at the time WH-Human-1 coronavirus. Phylogenetic analyis showed 89.1% similarity to SARS-like coronaviruses previously sampled from bats in China.
Proposed that novel coronavirus has higher transmissibility than SARS between humans.
SARS-CoV-2 shows discordant clustering with the Bat-SARS-like coronavirus sequences. Almost half of the virus’ genome is of a distinct lineage within the betacoronavirus, suggesting that spontaneous emergence of SARS-CoV-2 is unlikely.
Based on models studying the movement of people, this study posits a possibility of assymptomatic transmission. It is also one of the first studies advocating the importance of testing.
This study found that CR3022, a SARS-CoV-specific human monoclonal antibody, binds potently with SARS-CoV-2. Therefore, CR3022 may be a potential candidate for therapeutics; in contrast to other anti-SARS-CoV antibodies that fail to neutralize SARS-CoV-2.
Using the travel history of cases detected outside Wuhan, authors first estimated the mean incubation period to be 6.4 days, ranging from 2.1 to 11.1 days. They first suggested using these values for case definition.
The study found a viral isolate different from other 2019-nCoVs. An analysis of genomic sequences tenatively suggests that at least two different viral strains of 2019-nCoV may be involved in the outbreak. Caveat: confirmation of genomic sequences are necessary.
Using an interactive model, authors analyzed the impact of travel screening programs on coronavirus spread. They estimated that around half of infected travelers will be missed by screening programs, generally consisting of those who have not yet developed symptoms and are unaware of exposure.
SARS-CoV-2 enters cells via SARS-coronavirus receptor, ACE2, and cellular protease TMPRSS2. TMPRSS2 inhibitor and serum from convalescent SARS patient prevented entry of SARS-CoV-2. This highlights the similarities between SARS-CoV-2 and SARS-coronavirus infections and could identify a potential target for antiviral intervention.
Single-cell transcriptomes of lung, esophagus, gastric, ileum and colon showed that ACE2 is highly expressed in the respiratory tract and in absorptive enterocytes from ileum and colon; indicating that the digestive system may be another route for 2019-nCov infection.
The study generated a novel recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. Fusion proteins potently neutralized SARS-CoV and 2019-nCoV in vitro.
The study found specific expression of ACE2 in cholangiocytes (epithelial cells of the bile duct), tentatively suggesting that the liver damage observed in some infected patients may be caused by cholangiocyte dysfunction. Further studies will be needed to reinforce the relationship between SARS-CoV-2 and liver injury before these findings are incorporated into the clinical management of COVID-19 patients.
Authors evaluated the preparedness and vulnerability of African countries against the risk of importation of 2019-nCoV based on travel volumes from infected provinces in China to African countries. Authors identified countries with highest (Egypt, Algeria, and South Africa) and moderate risk with high vulnerabilities (Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, and Kenya), and called for intensifying surveillance and capacity building.
This work developed a coronavirus database (CoVdb)- an online genomics and proteomics analysis platform. The database annotates the genome of every strain and identifies possible ORFs of all strains available in Genebank. It also provides population genetics analysis, functional analysis and structural analysis on a historical and global scale. Accessed freely at http://covdb.popgenetics.net.
The authors suggest that ACE2-expressing small intestinal epithelium cells might be vulnerable to 2019-nCoV infection, and that diarrhea may serve as an indicator for infection. The authors suggest that clinicians should pay more attention to patients with diarrhea during the outbreak of pneumonia.
The study used hACE2 transgenic mice to study the pathogenicity of SARS-CoV-2. They define histopathology in the lungs, specific to transgenic mice and not observed in wild type mice. They propose this mouse model may facilitate the development of therapeutics and vaccines against SARS-CoV-2.
Initially, the basic reproductive number (R0) was estimated to be 2.2 to 2.7. This study integrates new estimates and high-resolution real-time human travel and infection data with mathematical models, and re-estimates the R0 value as being between 4.7 and 6.6.
Reviewed by the Mount Sinai Immunology review project
3.5 Å-resolution cryo-EM structure of the 2019-nCoV S trimer in the prefusion conformation; now published in Science at https://science.sciencemag.org/content/367/6483/1260
Early suggestion that the Iran likely had a large, undetected outbreak, which could complicate global containment.
Analysis of time course and prevalence of viral loads. Active replication of the virus in upper respiratory tract. No infectious virus from stool. Now published at Nature as https://www.nature.com/articles/s41586-020-2196-x#disqus_thread
Decay kinetics for the virus on various surfaces in varied environmental conditions, including plastic, metal and cardboard; now published as https://www.nejm.org/doi/10.1056/NEJMc2004973
Report of a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV). This cross-neutralizing antibody targets a communal epitope on these viruses and offers potential for prevention and treatment of COVID-19.
Modelling suggests that 1-1.5% of COVID-19 cases in China were fatal
Rhesus macaques previously infected with SARS-CoV-2 could not be reinfected with virus within a period of 28 days after symptoms were alleviated. Conclusions highly exploratory and based on preliminary data gathered from 4 rhesus macaques.
Models suggest that COVID-19 Infectiousness peaks at or before symptom onset, and 44% of transmissions could happen before symptom onset.
Debunked by Elizabeth Bik: https://scienceintegritydigest.com/2020/03/24/thoughts-on-the-gautret-et-al-paper-about-hydroxychloroquine-and-azithromycin-treatment-of-covid-19-infections/. Additional data from the lab behind this paper continues to be suspicious (https://twitter.com/houndcl/status/1248294470837133312)
Development and validation of serological assays for SARS-CoV-2 by comparing them to plaque reduction neutralisation assay (PRNT). Confirming S1 as specific antigen for SARS-CoV-2 testing, relative to S2 antigen.
Screening FDA-approved drugs for antiviral activity; See also: https://www.biorxiv.org/content/10.1101/2020.03.25.008482v1
The authors tested 19 epitope-HLA-binding prediction tools to assess 777 unique SARS-CoV-2 epitopes, that could bind 11 HLA allotypes. An in vitro assay showed that 174 epitopes formed a stable epitope-HLA complex: 48 were related to SARS and the remaining 126 were novel.
Massive collaborative effort to generate a SARS-CoV-2-human PPI map via affinity purification-ms; uncovered interactions with protein trafficking, translation, transcription and ubiquitination pathways; shared interactions with other viruses; 69 FDA-approved drugs that target/alter some of these interactions
Using modelling, the authors concluded that intermittent interventions for epidemic control in the United States may be needed until 2022 to keep prevalence within healthcare capacities.
The authors identified host transcriptional signatures in response to different modalities of SARS-CoV-2 infection, revealing similarities to and differences from other coronaviridiae and influenza infections
Characterisation of monoclonal antibodies from B cells of 8 human patients - display specific binding and neutralising activity for the virus; don’t cross-react with MERS/SARS coronavirus spike proteins; also covered here: https://twitter.com/davidrliu/status/1243377007016251400?s=20
Main results suggest that the higher evolutionary rate observed for genes encoding nucleocapsid, viral replicase and spike proteins, could represent a major barrier in the development of antiviral therapeutics 2019-nCoV.
Analysis of 535 preprints related to COVID-19 highlights the need for improved data sharing and reporting practices.
Suggests that high levels of the enzyme lactate dehydrogenase is a risk factor for severe COVID
An epidemiological study has found that differences in COVID-19 impact could potentially be attributed to the BCG vaccine offering a broader protection on respiratory infections than previously thought. Countries without universal BCG vaccinations (Italy and USA) are hit comparably worse by the corona virus than countries with universal long-standing BCG policies (Iran and China). [Credit: Tasha Aley (@tasha_aley), UCL/MRC LMCB - relayed to GD]
Site-specific mass spectometry reveals patterns of glycosylation on the SARS-CoV2 spike protein. Preprint related to: https://www.biorxiv.org/content/10.1101/2020.03.28.013276v1
The shortage of nucleic acid extraction kits for SARS-CoV-2 testing has led Danish scientists Anna S Fomsgaard and Maiken W. Rosenstierne to test alternatives. They found that the best approach is heating samples to 98 degrees Celsius for 5 minutes prior to RT-qPCR, which results in a 97.4% sensitivity and 100% specificity of SARS-CoV-2 detection. [Credit: Patricia Pascual-Vargas (@ppascualvargas), UCL - relayed to GD]
The seasonality of the virus will have a massive impact on isolation and social distancing policies around the world following the first wave of infections this winter. This paper suggests that there is currently no evidence that infection rates are lower in regions with higher temperatures.
In a study of 1099 confirmed COVID-19 patients, 12.3% of current smokers required mechanical ventilation, were admitted to an ICU, or died, compared to only 4.7% of non-smokers. This report shows that this effect might be due to upregulated levels of the ACE2 receptor caused by cigarette smoke.
Second report dealing with neutralising antibodies in convalescent serum, this time 25 samples from Singapore patients. Of the two immunodominant regions in the spike protein, one appears to be specific to SARS-CoV2 and one shared amongst coronaviruses
Intestinal human defensin (HD) 5, but not HD6, binds to ACE2 with a high affinity and blocks SARS-CoV-2 spike 1 protein (S1) binding. HD5 “cloak” on ACE2 binding domain was validated by molecular dynamic simulations, and HD5 preventative effect on SARS-CoV-2 binding was confirmed in intestinal epithelial cells.
The authors developed a single-enzyme RT-qPCR assay using thermostable reverse transcriptase (RT) /DNA polymerase (RTX) as a comparable alternative to commercial COVID-19 RT-qPCR assays that may be in short supply.
Authors used data from 117,000 confirmed COVID-19 patients world-wide to build a machine-learning model that predicts mortality in COVID-19 patients (“accuracy” = 93%). The model identified age and co-morbidity as key factors. Caveats: more interactions and other factors will be needed for this tool to aid in medical decision-making.
The authors summarise Risk Factors for COVID-19 by looking across multiple studies. Table 1 gives an especially useful overview of these patient characteristics along with the authors, patient pool sizes, and regions where these studies were conducted.
Suggests that higher levels of IL-6 may be predictive of patients who need ventillation. Follows similar work showing LDH levels may be predictive of disease severity
The authors use models that suggest that “herd immunity” is unfeasable, and call for strategies to “flatten the curve”.
Optimal design of 5’ and 3’ UTRs for potential SARS-CoV-2 mRNA vaccines
ACE2 has become an important research topic in relation to COVID-19 pathogenesis. This study mined around 7000 exosome from Italian genomes looking for variants of the ACE2 receptor, which has been proposed as the main host receptor for SARS-COV-2. Among three common missense changes, unreported in Easter Asia population, p.Asn720Asp is predicted to affect cleavage-dependent virion intake. Additional 30 missense variants were identified, some of which are predicted to affect the interaction with the spike protein. Caveats to this paper: the variants discovered that could change the way the virus interacts with the ACE2 receptor are rare. As these variants are so rare, they may notexplain the heterogeneity in disease outcomes in the general public. No correlations with patient data , all predictions from computational studies. Consequently, the hypothesis that these variants might explain higher mortality rates in Italy compared to China is probably over-stretched. [Additional credit: Giulia Paci, @giulia_paci, UCL LMCB]
Suggests that widespread use of facemasks is not supported by the evidence. However, use in high-risk situations (e.g. hospital settings) is beneficial
The authors themselves highlight some key limitations within their preprint. However, this data still supports the prevailing notions that testing and bed capacity are essential
Authors seek to provide 4 key clinical characteristics of severe COVID-19 by examining viral shedding, serological features, inflammatory response, and lung-lesions.
Authors evaluate levels of neutralising antibodies (NAbs) from recovered patients with clinical manifestations. Tentative results suggest correlation between humoral response and cellular immune response; with the caveat that experiments were only performed using plasma from patients with mild symptoms; further tests are needed for advanced cases to confirm correlation.
With an acute shortage of ventilators that are essential in the treatment of COVID-19 patients, this study describes a model whereby two patients can be ventilated using a single machine.
Using calculated basic reproduction numbers, the authors propose an exit strategy from lockdown: short periods of work interspersed with lockdown intervals. This strategy is designed to restrict spread and ensure that infected individuals are under lockdown when at their most infectious.
Negative results are often difficult to publish. However, when it is essential to understand what does not work as much as what does work, these negative results are highly important and very welcome. This study is an in vitro evaluation of the efficacy of HIV protease inhibitor darunavir (DRV) as potential antiviral treatment of COVID-19. In human caco-2 cells, clinically relevant concentrations of DRV didn’t show activity against SARS-COV-2. Antiviral activity was evaluated as cytopathogenic effect, scored by two methods. Most experiments were carried out in triplicate. Conflict of interest: Funding for this study was provided by Janssen Pharmaceutica. [Credit Giulia Paci (@giulia_paci), UCL LMCB]
Monoclonal antibodies isolated in 2003 from a SARS survivor neutralize the SARS-CoV-2 virus, and recognize a glycan-containing epitope that is conserved across the sarbecovirus subgenus (that includes SARS-CoV-1 and SARS-CoV-2)
There has been some evidence that suggests the BCG vaccine may provide a degree of immunity against COVID-19. This preprint suggests that another childhood vaccine, MMR may also be beneficial in providing protection against COVID-19
Comprehensive analysis of the characteristics of 4103 lab-confirmed COVID-19 patients in NYC. Strong associations with age, obesity, heart failure, and kidney disease with severe cases; weaker with race, tobacco usage, pulmonary disease. At early stages of hospitalisation, hypoxia even in the presence of supplemental oxygen and high levels of inflammation correlated strongly with severe disease states.
It has been suggested that ACE inhibitors used to treat hypertension or diabetes could upregulate ACE-2 and thereby exacerbate COVID-19 pathophysiology. Initial results on this small cohort (looking at outcomes for those who were receiving ACE inhibitors just before hospitalisation) suggest that this is not the case; the cohort was not large enough to look for positive outcomes, if any.
Supports the hypothesis that there is no strong benefit of CQ treatment, and that doses should be kept low to avoid a potentially adverse impact; a good example of how to cautiously interpret data in the middle of a swirling controversy
Doudna and colleagues share their experience, from ensuring regulatory compliance to cross-validating RT-PCR results against testing benchmarks, of converting an academic research lab to a COVID-19 testing facility within the duration of approximately one month.
Antibodies to the receptor-binding domain (RBD) of the viral spike protein were highly effective against SARS-CoV-1; immunisation with the SARS-CoV-2 RBD produced potent neutralising antibodies in rats. Importantly, these did not result in antibody-dependent enhancement of viral entry, a potential concern in the way of constructing an RBD-based vaccine.
Computational tool to model the effect of various knockdowns and perturbations on the host cell SARS-CoV-2 response network (https://covid.pages.uni.lu/map_curation); tool available at http://hipathia.babelomics.org/covid19/
Founder mutations in 90% of SARS-CoV-2 sequences from geographically unrelated countries (USA, China and Australia), of which 63% of mutations are missense. Computational analysis of primer sets predict potential consequences on amplification efficiency–and therefore, performance–of RT-qPCR tests.
The study suggests environmental temperature may affect number of COVID-19 cases. By comparing different regions across 5 countries, this study correlates differential daily temperature correlated with average daily cumulative cases of COVID-19. An important caveat is that this preprint has not explored other potential differences that might have existed between the regions examined, like differences in policies or population density between the regions.
A method has been developed to decontaminate N95 filtering facepiece respirators (FFRs) for reuse by healthcare workers. Applying a heat and humidity procedure for up to five cycles of did not affect filtration efficiency or mask fitting. Further work is required to confirm viral inactivation of SARS-CoV-2, along with its scalability using larger equipment.
Hydroxychloroquine (HCQ) displayed no clinical benefit, in this study emulating a target trial across 4 French hospitals including 181 patients with SARS-CoV-2 pneumonia. Primary endpoints for this study were transfer to ICU and/or death.
Preliminary data shows FDA-approved anti-rheumatoid drug, auranofin, inhibited SARS-CoV-2 replication and pro-inflammtory cytokine production in a human cell line at low micro molar concentrations. This drug has not previously been known for antiviral properties and the mechanism remains unclear, therefore, further studies are required to evaulate the use of this drug for treatment of COVID-19.
Serological (antibody) studies are desparately needed to better identify the true percentage of the population that have been infected. However, caution should be applied to interpreting the results of this study for mulitple reasons, see https://twitter.com/DiseaseEcology/status/1251225273871134721?s=19 for a detailed deconstruction
Due to the time needed to conduct immunlogical studies, there is a dearth of information relating to SARS-CoV-2 immunity. This review summarises current knowledge in other coronaviruses, and suggests how it may be applied to COVID-19.
The increasing calls from governments around the world for people to wear facemasks in public may exacerbate the shortage of PPE for frontline workers. This preprint investigates the protective ability of cloth face coverings, and tentatively concludes that they may indeed offer a certain amount of protection.
This work describes an isothermal assay platform for rapid detection and surveillance of SARS-CoV2 infection. A whole-transcriptome survey of over 450 viral, host and environmental samples in New York City (NYC) was also performed to identify phylogenetics of NYC COVID infections and host risk factors.
Authors found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19. An association of increased overall mortality was identified in patients treated with hydroxychloroquine alone (however this did not hold true when compared to the control group).
Self-collected saliva samples provided similar, if not more sensitive and consistent results compared to patient-matched nasopharyngeal swabs for the detection of SARS-CoV-2. More data are required to determine efficacy in mild/asympotomatic cases with lower viral load. Supports recent study: https://www.medrxiv.org/content/10.1101/2020.04.11.20062372v1
The authors perform single-cell RNA sequencing (scRNA-seq) to peripheral blood mononuclear cells of 7 patients hospitalized with confirmed COVID-19 and 6 healthy controls. This is a powerful technique and the first scRNA-seq study looking at blood immune cells. Due to the novelty surrounding these findings, further validation of this technique will be needed.
TwinsUK study collected data in the C-19 Covid symptom tracker app (https://covid.joinzoe.com/) and claimed to find heritability for susceptibility to infection and severity of symptoms. Although this app is a useful resource, many caveats have been identified in this study, as discussed here: https://twitter.com/bristimtom/status/1254030253854543872.
Comparison of COVID-19 and seasonal influenza raw count deaths, as opposed to CDC-adjusted estimations, shows 21.1x-21.4x more COVID-19 deaths in New York City from Feb 1st to April 18th 2020. Limitations include: under- or over-reporting of deaths, lags in reporting, and differential peaks of each disease.
Japanese study testing for SARS-CoV-2 antibodies found prevalence of positivity at 2.7%, 396 to 858 fold higher than PCR confirmed cases of COVID. These results should be considered with caution due to the limitations discussed in preprint: (1) samples were obtained from clinic outpatients (2) potential test cross-reactivity with other viruses.
This study used observational data to compare epidemic trajectories before and after full lockdowns, and suggests that these measures may not have reduced deaths in Western Europe.
This retrospective study identifies an association between hydroxychloroquine use and decreased mortality, and corroborates the in vitro antiviral effects of hydroxychloroquine. Caveat: the approval of the study design has been questioned by other researchers (http://disq.us/p/28zsoh0)
Parsing the heterogeneity of individuals susceptible to COVID-19, the authors concluded that herd immunity may be achieved with a lower percentage of immune individuals than previous estimates suggest.
Development of a rapid, high-throughput, semi-automated mass spectrometry platform helps identify 27 biomarkers in plasma samples that are differentially expressed between mild and severe forms of COVID-19. Highlights potential therapeutic targets linked to IL-6 signaling.
In this multicenter prospective observational study, the authors found that chloroquine, even at low doses, decreased the time taken for viral RNA to reach undetectable levels and reduced the duration of fever in patients with COVID-19. Based on the results, the authors tentatively suggest chloroquine’s potential role in COVID-19 treatment, but emphasise the need for further studies for chloroquine’s efficacy and safety.
Using PCR and ELISA, the authors found that most confirmed COVID-19 patients seroconverted after infection, suggesting that COVID-19 patients may develop humoral immunity to reinfection.
In this study consisting of 8 weekly serosurveys spanning 1335 participants from 633 households, the authors found that Geneva, Switzerland is still far from achieving herd immunity.
Important study describing the factors influencing COVID-19 deaths. However, the interpretation of the results requires care: https://twitter.com/EpiEllie/status/1258607280133681155?s=19
OpenSAFELY is a new pseudoymised analytics platform created from NHS England primary care electronic health records. Preliminary data from this source (n = 17,425,445) suggest an increased risk of COVID-19 hospital death associated with male gender, older age, prior medical conditions (e.g. uncontrolled diabetes and severe asthma), non-white ethnicity (African-American or Asian origin), and deprivation.
In this retrospective observational study, the authors found that the addition of zinc sulfate to regimens with hydroxychloroquine and azithromycin reduced mortality and transition to hospice; benefits were mainly found in patients not requiring ICU level of care.
Comparison of nucleic acid amplification tests for SARS-CoV-2 suggest that the Abbot ID NOW COVID-19 test had a third more false negative results. Concerns have been raised that the collection methods and transport of these samples were not compatible with this test.
Tentative but promising results suggesting that injection of the SARS-Cov-2 spike protein ChAdOx1 can vaccinate monkeys and protect against lung damage. https://twitter.com/davidrliu/status/1260888279882268673?s=20
Authors quantify excess deaths (week by week, from March) in Sweden. COVID19 has taken 2-3 years from life expectancy in Sweden. Thread: https://twitter.com/NAChristakis/status/1262012815663149058?s=19
Approximately 10% of SARS-CoV-2 negative blood donors with recent HCoV infections displayed IgG cross-reactivity towards SARS-CoV-2 S protein. Limitations discussed in review: https://www.immunology.ox.ac.uk/covid-19/covid-19-immunology-literature-reviews/pre-existing-and-de-novo-humoral-immunity-to-sars-cov-2-in-humans
In this retrospective cohort study, the authors explored the use of hydroxychloroquine with antibiotics, or lopinavir or ritonavir with antibiotics; and compared these arms to a third conservative treatment control arm. The authors found that hydroxychloroquine with antibiotics led to better viral clearance, reduced hospital stay, and enhanced cough symptom resolution, but caution that toxicity was not measured in their study.
Infection fatality rates from seroprevalence studies are lower than original estimates made in the early days of the COVID-19 pandemic. Caveats: Concerns regarding the paper’s methodology have been raised by other researchers, such as https://twitter.com/GidMK/status/1262956011872280577
Tested over 15,000 SARS-CoV-2 genomes and found no evidence for strains acquiring mutations that make them more transmissible
Sequenced 112 genomes and found 1-10% of infected individuals are responsible for 80% of secondary infections using phylogenetic trees. Strong suggestions against the possibility of herd immunity
SARS-CoV-2 RNA concentration in primary sewage sludge highly correlated with COVID-19 epidemiological curve and local hospital admissions, with a seven- to three- day leading indication, respectively.
Preprints represent ~40% of the COVID19 literature
The authors identified a consensus peripheral blood immunological signature across a heterogeneous population. Implications extend to using certain components for prognosis, as well as boosting the understanding of the underlying pathogenesis of COVID-19.
The authors attributed the successful suppression of COVID-19 transmission in the first wave of the pandemic in Hong Kong to a combination of two key public health measures. The focus on early and near complete identification of cases interrupted transmission; while a complete lockdown was avoided with the implementation of more general physical distancing community measures.
Authors reported that a D614G mutation in the SARS-CoV-2 spike protein may increase its infectivity.
The authors showed that inhaled corticosteroid (ICS) administration attenuated pulmonary expression of ACE2 in various human and animal models. Because ACE2 has been reported to facilitate cellular entry of SARS-CoV-2, the authors suggest that ICS may modulate the clinical course of COVID-19.
Through the analysis of ACE2 levels, the authors concluded that COVID-19 may adversely affect colon adenocarcinoma (COAD) patient survival outcomes. Therefore, additional preventive measures may be needed to protect patients from COVID-19.
Authors’ findings support recent reports that a D614G mutation in the SARS-CoV-2 Spike (S) protein improves its ability to transduce host cells. Specifically, the G614 variant was more resistant to cleavage than the D614 variant, which may improve the ability of newly-assembled virions to include more receptor binding-capable S protein.
Using a lentiviral system, authors reported three key findings: 1) SARS-CoV-2-Spike (S) protein-mediated cell entry strongly depends on TMPRSS2 coexpression, 2) the SARS-CoV-2 D614G mutant exhibited activity for entry approximately 3.5x that of the wild type, and 3) despite the biological and structural changes, the antigenicity of the D614G mutant did not vary significantly from the wild type.
The authors designed a thermostable Spike (S) protein trimer, which they envision would be useful for research in vaccinology, diagnostics, and other scientific research involving SARS-CoV-2.
Using a quantitative deep mutational scanning approach, the authors determined the influence of mutations in the receptor binding domain (RBD) on the protein’s binding affinity to the ACE2 receptor. The authors identified mutations that increased binding affinity between the RBD, as well as patterns relating to the trade-off between protein stability and binding affinity.
In this preprint, the authors screened through 3,000 drugs in monkey (Vero), human hepatocyte (Huh7.5), and human lung epithelial (Calu-3) cells. They identified 9 antiviral candidates active against SARS-CoV-2 in the Calu-3 cells.
Using a Golden Syrian hamster in vivo model, the authors found that a single-dose of rVSV-∆Gspike vaccine was safe and efficacious in protecting against a SARS-CoV-2 challenge.
The authors sequenced SARS-CoV-2 isolates from symptomatic COVID-19 cases in a suburban and rural community in the southeastern US. Their results suggested that the SARS-CoV-2 Spike protein D614G mutant (associated with greater pathogenecity) is the dominant strain in the US.
This preprint is a preliminary report from the RECOVERY trial: dexamethasone reduced deaths in patients receiving mechanical ventilation as well as in patients receiving medical oxygen without mechanical ventilation, but did not reduce mortality in patients not receiving respiratory support at randomisation.
Using in situ cryo-electron tomography, the authors visualised double-stranded RNA within double-membrane vesicles. They found that membrane formation is influenced by the spike trimer and viral ribonucleoprotein complex recruitment into virion budding sites. These findings may have important implications for SARS-CoV-2 antiviral discovery.
Using a mouse model of ischemia-reperfusion lung injury, the authors showed that Fostamatnib induces the down-regulation and internalization of MUC1, and reduces the expression of MUC1 in the lung.
The authors describe an inexpensive, manually-powered diagnostic to detect COVID-19 RNA from saliva. This hardware is compatible with the LAMP assay described by Rabe and Cepko (2020).
By investigating the histology of various tissues isolated from post-mortems of fatal COVID-19 cases, the authors concluded that death from COVID-19 may mainly be attributed to the immune response rather than tissue-specific injury.
The authors found a decline in antibody titres a few months after patients were exposed to COVID-19. These findings may have important implications in preventing reinfection by SARS-CoV-2, as well as in vaccine development. On the other hand, they may also be natural–following challenge, antibody titres naturally decrease over time.
The authors established the mechanistic association between SARS-CoV-2 infection and clinical manifestation of COVID-19. The presence of antibodies targeting the viral spike protein from patient blood triggers a cytokine storm in activated human macrophages, which compromises the vascular endothelial barrier and promotes blood coagulation.
In this study, the authors investigated the effectiveness of convalescent plasma in treating COVID-19 in India.