COVID 19 Special Collection
COVID-19 (SARS-CoV-2) Special Collection
Latest COVID-19 Articles
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Research Article
Competitive SARS-CoV-2 Serology Reveals Most Antibodies Targeting the Spike Receptor-Binding Domain Compete for ACE2 Binding
With the emergence and continued spread of the SARS-CoV-2 virus, and of the associated disease, coronavirus disease 2019 (COVID-19), there is an urgent need for improved understanding of how the body mounts an immune response to the virus. Here, we developed a competitive SARS-CoV-2 serological assay that can simultaneously determine whether an individual has developed antibodies against the SARS-CoV-2 Spike protein receptor-binding domain (RBD) and measure the proportion of these antibodies that block interaction with the human angiotensin-converting enzyme 2 (ACE2) required for viral entry. Using this assay and 144 SARS-CoV-2 patient serum samples, we found that a majority of anti-RBD antibodies compete for ACE2 binding. These results not only highlight the need to design vaccines to generate such blocking antibodies but also demonstrate the utility of this assay to rapidly screen patient sera for potentially neutralizing antibodies.
16 September 2020, mSphere
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Minireview
Potential applications of human viral metagenomics and reference materials: considerations for current and future viruses
Viruses are ubiquitous particles comprised of genetic material that can infect bacteria, archaea, fungi, as well as human and other animal cells. Given that determining virus composition and function in association with states of human health and disease is of increasing interest, we anticipate that the field of viral metagenomics will continue to expand and be applied in a variety of areas ranging from surveillance to discovery, and will rely heavily upon the continued development of reference materials and databases. Information regarding viral composition and function readily translate into biological and clinical applications, including the rapid sequence identification of pathogenic viruses in various sample typ–es. However, viral metagenomic approaches often lack appropriate standards and reference materials to enable cross-study comparisons and assess potential biases which can be introduced at the various stages of collection, storage, processing, and sequence analysis. In addition, implementation of appropriate viral reference materials can aid in the benchmarking of current and development of novel assays for virus identification, discovery, and surveillance. As the field of viral metagenomics expands and standardizes, results will continue to translate into diverse applications.
Accepted Manuscript Posted 11 September 2020, AEM; Final Article Posted 28 October 2020
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Research Article
Serological Assays Estimate Highly Variable SARS-CoV-2 Neutralizing Antibody Activity in Recovered COVID19 Patients
The development of neutralizing antibodies (nAb) against SARS-CoV-2, following infection or vaccination, is likely to be critical for the development of sufficient population immunity to drive cessation of the COVID19 pandemic. A large number of serologic tests, platforms and methodologies are being employed to determine seroprevalence in populations to select convalescent plasmas for therapeutic trials, and to guide policies about reopening. However, tests have substantial variability in sensitivity and specificity, and their ability to quantitatively predict levels of nAb is unknown. We collected 370 unique donors enrolled in the New York Blood Center Convalescent Plasma Program between April and May of 2020. We measured levels of antibodies in convalescent plasma using commercially available SARS-CoV-2 detection tests and in-house ELISA assays and correlated serological measurements with nAb activity measured using pseudotyped virus particles, which offer the most informative assessment of antiviral activity of patient sera against viral infection. Our data show that a large proportion of convalescent plasma samples have modest antibody levels and that commercially available tests have varying degrees of accuracy in predicting nAb activity. We found the Ortho Anti-SARS-CoV-2 Total Ig and IgG high throughput serological assays (HTSAs), as well as the Abbott SARS-CoV-2 IgG assay, quantify levels of antibodies that strongly correlate with nAb assays and are consistent with gold-standard ELISA assay results. These findings provide immediate clinical relevance to serology results that can be equated to nAb activity and could serve as a valuable ‘roadmap’ to guide the choice and interpretation of serological tests for SARS-CoV-2.
Accepted Manuscript Posted 11 September 2020, JCM; Final Article Posted 18 November 2020
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Observation
Antiviral Activity of Type I, II, and III Interferons Counterbalances ACE2 Inducibility and Restricts SARS-CoV-2
Repurposing existing, clinically approved, antiviral drugs as COVID-19 therapeutics is a rapid way to help combat the SARS-CoV-2 pandemic. Interferons (IFNs) usually form part of the body’s natural innate immune defenses against viruses, and they have been used with partial success to treat previous new viral threats, such as HIV, hepatitis C virus, and Ebola virus. Nevertheless, IFNs can have undesirable side effects, and recent reports indicate that IFNs upregulate the expression of host ACE2 (a critical entry receptor for SARS-CoV-2), raising the possibility that IFN treatments could exacerbate COVID-19. Here, we studied the antiviral- and ACE2-inducing properties of different IFN types in both a human lung cell line model and primary human bronchial epithelial cells. We observed differences between IFNs with respect to their induction of antiviral genes and abilities to enhance the cell surface expression of ACE2. Nevertheless, all the IFNs limited SARS-CoV-2 replication, suggesting that their antiviral actions can counterbalance increased ACE2.
10 September 2020, mBio
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Research Article
Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2 Infected Syrian Hamsters
Syrian hamsters are in use as a model of disease caused by SARS-CoV-2. Pathology is pronounced in the upper and lower respiratory tract and disease signs and endpoints include weight loss, viral RNA and/or infectious virus in swabs and organs (e.g. lungs). However, a high dose of virus is needed to produce disease and the disease resolves rapidly. Here, we demonstrate that immunosuppressed hamsters are susceptible to low doses of virus and develop more severe and prolonged disease. We demonstrate the efficacy of a novel neutralizing monoclonal antibody using the cyclophosphamide transient suppression model. Furthermore, we demonstrate that RAG2 knockout hamsters develop severe/fatal disease when exposed to SARS-CoV-2. These immunosuppressed hamster models provide researchers new tools for evaluating therapies and vaccines, and understanding COVID-19 pathogenesis.
Accepted Manuscript Posted 8 September 2020, JVI; Final Article Posted 27 October 2020
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Research Article
An Early Pandemic Analysis of SARS-CoV-2 Population Structure and Dynamics in Arizona
As the COVID-19 pandemic swept across the United States, there was great differential impact on local and regional communities. One of the earliest and hardest hit regions was in New York, while at the same time Arizona (for example) had low incidence. That situation has changed dramatically, with Arizona now having the highest rate of disease increase in the country. Understanding the roots of the pandemic during the initial months is essential as the pandemic continues and reaches new heights. Genomic analysis and phylogenetic modeling of SARS-COV-2 in Arizona can help to reconstruct population composition and predict the earliest undetected introductions. This foundational work represents the basis for future analysis and understanding as the pandemic continues.
4 September 2020, mBio
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Research Article
A Direct Comparison of Enhanced Saliva to Nasopharyngeal Swab for the Detection of SARS-CoV-2 in Symptomatic Patients
The ongoing COVID-19 pandemic has resulted in shortages in nasopharyngeal swabs (NPS) and viral transport media, necessitating the search for alternate diagnostic specimens, such as saliva. We directly compared matched saliva and NPS specimens from symptomatic patients suspected of having COVID-19. An enhanced saliva specimen (ie strong sniff, elicited cough, and collection of saliva/secretions) was collected without transport media prior to NPS from 224 patients with symptoms deemed consistent with COVID-19. Both specimens were tested with the CDC 2019 nCoV Real-Time RT-PCR Diagnostic Panel (4 February 2020 version), with the NPS result used as the reference standard. Of the 216 patients included in the final analysis, there was a 100% Positive Percent Agreement (38/38 positive specimens) and 99.4% Negative Percent Agreement (177/178 negative specimens). The one discrepant specimen had the presence of SARS-CoV-2 confirmed in the saliva specimen using an alternate FDA EUA assay. The overall mean difference in crossing threshold (Ct) values for the positive NPS and saliva specimens was -3.61 (95% C.I. -5.78 to -1.44, p = 0.002). An enhanced saliva specimen performed as well as NPS for the qualitative detection of SARS-CoV-2 in symptomatic patients, albeit the overall mean viral load in saliva was lower.
Accepted Manuscript Posted 3 September 2020, JCM; Final Article Posted 21 October 2020
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Research Article
Evolution of Early SARS-CoV-2 and Cross-Coronavirus Immunity
A critical step to ending the spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the ability to detect, diagnose, and understand why some individuals develop mild and others develop severe disease. For example, defining the early evolutionary patterns of humoral immunity to SARS-CoV-2, and whether prevalent coronaviruses or other common infections influence the evolution of immunity, remains poorly understood but could inform diagnostic and vaccine development. Here, we deeply profiled the evolution of SARS-CoV-2 immunity, and how it is influenced by other coinfections. Our data suggest an early and rapid rise in functional humoral immunity in the first 2 weeks of infection across antigen-specific targets, which is negligibly influenced by cross-reactivity to additional common coronaviruses or common respiratory infections. These data suggest that preexisting receptor binding domain-specific immunity does not influence or bias the evolution of immunity to SARS-CoV-2 and should have negligible influence on shaping diagnostic or vaccine-induced immunity.
2 September 2020, mSphere
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Observation
A Simplified Quantitative Real-Time PCR Assay for Monitoring SARS-CoV-2 Growth in Cell Culture
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, is continuing to cause immense respiratory disease and social and economic disruptions. Conventional assays that monitor SARS-CoV-2 growth in cell culture rely on costly and time-consuming RNA extraction procedures, hampering progress in basic SARS-CoV-2 research and development of effective therapeutics. Here, we developed a simple quantitative real-time PCR assay to monitor SARS-CoV-2 growth in cell culture supernatants that does not necessitate RNA extraction and that is as accurate and sensitive as existing methods. In a proof-of-concept screen, we found that E64D, apilimod, EIPA, and remdesivir can substantially impede SARS-Cov-2 replication, providing novel insight into viral entry and replication mechanisms. In addition, we show that this approach is easily adaptable to numerous other RNA and DNA viruses. This simplified assay will undoubtedly expedite basic SARS-CoV-2 and virology research and be amenable to use in drug screening platforms to identify therapeutics against SARS-CoV-2.
2 September 2020, mSphere
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Research Article
Low Baseline Pulmonary Levels of Cytotoxic Lymphocytes as a Predisposing Risk Factor for Severe COVID-19
COVID-19 is caused by the highly contagious coronavirus SARS-CoV-2 and currently has detrimental human health, community, and economic impacts around the world. It is unclear why some SARS-CoV-2-positive individuals develop severe COVID-19 symptoms, which can be fatal, while others only develop mild symptoms. In the absence of an effective and widely available vaccine, it is of paramount importance that we identify risk factors for development of severe symptoms to be able to improve treatment approaches. The ACE2 gene encodes the receptor on human cells that the virus uses to infect these cells. This study finds that if the lungs of healthy individuals have high levels of ACE2, they typically have low levels of the immune cells that eliminate viruses. Therefore, some individuals may develop severe COVID-19 due to simultaneous high levels of the virus receptor and low levels of immune cells that eradicate the virus in their lungs.
1 September 2020, mSystems
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Research Article
Removal of remdesivir's metabolite GS-441524 by hemodialysis in a double lung transplant recipient with COVID-19
Remdesivir has reported efficacy against SARS-CoV-2 in vitro and in vivo. Drug-drug interactions limit therapeutic options in transplant patients. Remdesivir and its metabolite GS-441524 are excreted principally in urine. In ICU settings, in which multiple organ dysfunctions can occur rapidly, hemodialysis may be a viable option for maintaining remdesivir treatment, while improving tolerance, by removing both remdesivir's metabolite (GS-441524) and SEBCD. Additional studies may prove informative, particularly in the evaluations of therapeutic options for COVID-19.
Accepted Manuscript Posted 31 August 2020, AAC; Final Article Posted 20 October 2020
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Research Article
SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has caused a global pandemic of COVID-19 resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >20 million people worldwide with >5 million cases in the US (August 11th, 2020). The development of diagnostic and research tools to determine infection and vaccine efficacy are critically needed. We have developed multiple serologic assays using newly designed SARS-CoV-2 reagents for detecting the presence of receptor-binding antibodies in sera. The first assay is SPR-based and can quantitate both antibody binding to the SARS-CoV-2 spike protein and blocking to the Angiotensin-converting enzyme 2 (ACE2) receptor in a single experiment. The second assay is ELISA-based and can measure competition and blocking of the ACE2 receptor to the SARS-CoV-2 spike protein with anti-spike antibodies. The assay is highly versatile, and we demonstrate the broad utility of the assay by measuring antibody functionality of sera from small animals and non-human primates immunized with an experimental SARS-CoV-2 vaccine. In addition, we employ the assay to measure receptor-blocking of sera from SARS-CoV-2 infected patients. The assay is shown to correlate with pseudovirus neutralization titers. This type of rapid, surrogate neutralization diagnostic can be employed widely to help study SARS-CoV-2 infection and for assessing efficacy of vaccines.
Accepted Manuscript Posted 27 August 2020, JCM; Final Article Posted 21 October 2020
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Genome Sequences
Four SARS-CoV-2 Genome Sequences from Late April in Stockholm, Sweden, Reveal a Rare Mutation in the Spike Protein
Here, we report four coding-complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences from Stockholm, Sweden, sampled in late April 2020. A rare variant at bp 23463 of the SARS-CoV-2 genome was found, which corresponds to the S1 subunit of the spike protein, changing an arginine (R) residue to histidine (H).
27 August 2020, MRA
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Letter to the Editor
High incidence of false positive results in patients with other acute infections, using the LIAISON® SARS-CoV-2 commercial chemiluminescent micro-particle immunoassay for detection of IgG anti SARS-CoV-2 antibodies
Coronavirus disease 19 (COVID-19), caused by SARS-CoV-2 is a major pandemic (2).…
Accepted Manuscript Posted 26 August 2020, JCM; Final Article Posted 21 October 2020
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Research Article
Development of a fluorescence based, high-throughput SARS-CoV-2 3CLpro reporter assay
The COVID-19 pandemic has already led to more than 700,000 deaths and innumerable changes to daily life worldwide. Along with development of a vaccine, identification of effective antivirals to treat infected patients is of the highest importance. However, rapid drug discovery requires efficient methods to identify novel compounds that can inhibit the virus. In this work, we present a method for identifying inhibitors of the SARS-CoV-2 main protease, 3CLpro. This reporter-based assay allows for antiviral drug screening in human cell culture at biosafety level-2 (BSL2) with high-throughput compatible sample processing and analysis. This assay may help identify novel antivirals to control the COVID-19 pandemic.
Accepted Manuscript Posted 26 August 2020, JVI; Final Article Posted 27 October 2020