COVID 19 Special Collection
COVID-19 (SARS-CoV-2) Special Collection
Latest COVID-19 Articles
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Opinion/Hypothesis
Can Unconventional Immunomodulatory Agents Help Alleviate COVID-19 Symptoms and Severity?
Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce increased levels of a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines, including interleukin-1 (IL-1), IL-6, CCL2 protein, and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes the following four unconventional but commercially accessible immunomodulatory agents that can be employed in clinical trials to evaluate their effectiveness at alleviating disease symptoms and severity: low-dose oral interferon alpha, microdose DNA, low-dose thimerosal, and phytocannabinoids.
13 May 2020, mSphere
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Minireview
COVID-19: Learning from Lessons To Guide Treatment and Prevention Interventions
Coronavirus disease 2019 (COVID-19) is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and first emerged in December 2019 in Wuhan, Hubei province, China. Since then, the virus has rapidly spread to many countries. While the outbreak in China appears to be in decline, the disease has spread across the world, with a daily increase in the number of confirmed cases and infection-related deaths. Here, we highlight (i) the lessons that have been learnt so far and how they will benefit reducing the impact of COVID-19 disease and (ii) an update on the status of drug treatment and vaccine development to prevent COVID-19 and potential future related pandemics. Although the mortality rate is clearly higher than for influenza, the rate does seem to vary from country to country, possibly reflecting differences in how rapidly local health authorities respond to isolate and effectively care for the affected population. Drugs are urgently needed for both prophylaxis and the treatment of severely ill patients; however, no proven effective therapies for SARS-CoV-2 currently exist. A number of drugs that have been approved for other diseases are being tested for the treatment of COVID-19 patients, but there is an absence of data from appropriately designed clinical trials showing that these drugs, either alone or in combination, will prove effective. There is also a global urgency to develop a vaccine against COVID-19, but development and appropriate testing will take at least a year before such a vaccine will be globally available. This review summarizes the lessons learnt so far from the COVID-19 pandemic, examines the evidence regarding the drugs that are being tested for the treatment of COVID19, and describes the progress made in efforts to develop an effective vaccine.
13 May 2020, mSphere
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Research Article
Open Development and Clinical Validation Of Multiple 3D-Printed Nasopharyngeal Collection Swabs: Rapid Resolution of a Critical COVID-19 Testing Bottleneck
The SARS-CoV-2 pandemic has caused a severe international shortage of the nasopharyngeal swabs that are required for collection of optimal specimens, creating a critical bottleneck blocking clinical laboratories' ability to perform high-sensitivity virological testing for SARS-CoV-2. To address this crisis, we designed and executed an innovative, cooperative, rapid-response translational-research program that brought together healthcare workers, manufacturers, and scientists to emergently develop and clinically validate new swabs for immediate mass production by 3D printing. We performed a multi-step preclinical evaluation on 160 swab designs and 48 materials from 24 companies, laboratories, and individuals, and shared results and other feedback via a public data repository (http://github.com/rarnaout/Covidswab/). We validated four prototypes through an institutional review board (IRB)-approved clinical trial that involved 276 outpatient volunteers who presented to our hospital's drive-through testing center with symptoms suspicious for COVID-19. Each participant was swabbed with a reference swab (the control) and a prototype, and SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) results were compared. All prototypes displayed excellent concordance with the control (K=0.85-0.89). Cycle-threshold (Ct) values were not significantly different between each prototype and the control, supporting the new swabs' non-inferiority (Mann-Whitney U [MWU] p>0.05). Study staff preferred one of the prototypes over the others and the control swab overall. The total time elapsed between identification of the problem and validation of the first prototype was 22 days. Contact information for ordering can be found at http://printedswabs.org. Our experience holds lessons for the rapid development, validation, and deployment of new technology for this pandemic and beyond.
Accepted Manuscript Posted 11 May 2020, JCM; Final Article Posted 23 July 2020
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Commentary
Understanding, verifying and implementing Emergency Use Authorization molecular diagnostics for the detection of SARS-CoV-2 RNA
The SARS-CoV-2 pandemic has brought a new wave of challenges to health care, particularly in the area of rapid diagnostic test development and implementation. Acute diagnosis of COVID-19 infection is critically dependent on detection of SARS-CoV-2 RNA from clinical specimens (e.g. nasopharyngeal swabs). While laboratory-developed testing for SARS-CoV-2 is an essential component of diagnostic testing for this virus, the majority of clinical microbiology laboratories are dependent on commercially available SARS-CoV-2 molecular assays. In contrast to assays approved or cleared by the Food and Drug Administration for in vitro diagnostic use, assays for the detection of SARS-CoV-2 nucleic acids have Emergency Use Authorization (EUA) from the FDA. Outside of highly specialized academic and commercial laboratory settings, clinical microbiology laboratories are likely unfamiliar with EUA classification and thus assay verification can be daunting. Further compounding anxiety for laboratories are major issues with supply chain that are dramatically affecting the availability of test reagents and requiring laboratories to implement multiple commercial EUA tests. Here, we describe guidance for the verification of assays with EUA for the detection of SARS-CoV-2 nucleic acid from clinical specimens.
Accepted Manuscript Posted 7 May 2020, JCM; Final Article Posted 23 July 2020
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Research Article
Comparison of Two High-Throughput Reverse Transcription-Polymerase Chain Reaction Systems for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as the cause of a worldwide pandemic. Many commercial SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) assays have received Emergency Use Authorization from the United States Food and Drug Administration. However, there are limited data describing their performance, in particular the performance of high-throughput SARS-CoV-2 RT-PCR systems. We analyzed the diagnostic performance of two high-throughput systems: cobas 6800 and Panther Fusion, and their associated RT-PCR assays with a collection of 389 nasopharyngeal specimens. The overall percent agreement between the platforms was 96.4% (375/389). Cohen's kappa analysis rated the strength of agreement between the two platforms as “almost perfect” (K = 0.922; standard error, 0.051). Furthermore, there was no significant difference between corresponding cycle threshold values generated on the two systems (P value = 0.88; Student's t test). Taken together, these data imply both platforms can be considered comparable in terms of their clinical performance. We believe this information will be useful for those who have already adopted these platforms or are seeking to implement high-throughput RT-PCR testing to stem the SARS-CoV-2 pandemic.
Accepted Manuscript Posted 7 May 2020, JCM; Final Article Posted 23 July 2020
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Research Article
Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence in Boise, Idaho
Coronavirus disease-19 (COVID19), the novel respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with severe morbidity and mortality. The rollout of diagnostic testing in the United States was slow, leading to numerous cases that were not tested for SARS-CoV-2 in February and March 2020, necessitating the use of serological testing to determine past infections. Here, we evaluated the Abbott SARS-CoV-2 IgG test for detection of anti-SARS-CoV-2 IgG antibodies by testing 3 distinct patient populations. We tested 1,020 serum specimens collected prior to SARS-CoV-2 circulation in the United States and found one false positive, indicating a specificity of 99.90%. We tested 125 patients who tested RT-PCR positive for SARS-CoV-2 for which 689 excess serum specimens were available and found sensitivity reached 100% at day 17 after symptom onset and day 13 after PCR positivity. Alternative index value thresholds for positivity resulted in 100% sensitivity and 100% specificity in this cohort. We tested 4,856 individuals from Boise, Idaho collected over one week in April 2020 as part of the Crush the Curve initiative and detected 87 positives for a positivity rate of 1.79%. These data demonstrate excellent analytical performance of the Abbott SARS-CoV-2 IgG test as well as the limited circulation of the virus in the western United States. We expect the availability of high-quality serological testing will be a key tool in the fight against SARS-CoV-2.
Accepted Manuscript Posted 7 May 2020, JCM; Final Article Posted 23 July 2020
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Genome Sequences
Near-Complete Genome Sequence of a 2019 Novel Coronavirus (SARS-CoV-2) Strain Causing a COVID-19 Case in Peru
A near-complete genome sequence was obtained for a novel coronavirus (SARS-CoV-2) strain obtained from an oropharyngeal swab from a Peruvian patient with coronavirus syndrome (COVID-19) who had contact with an individual who had returned to Peru from travel to Italy.
7 May 2020, MRA
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Research Article
Inhibition of SARS-CoV-2 infection by the cyclophilin inhibitor Alisporivir (Debio 025)
Cyclophilins play a key role in the lifecycle of coronaviruses. Alisporivir (Debio 025) is a non-immunosuppressive analogue of cyclosporin A with potent cyclophilin inhibition properties. Alisporivir reduced SARS-CoV-2 RNA production in a dose-dependent manner in VeroE6 cell line, with an EC50 of 0.46±0.04 µM. Alisporivir inhibited a post-entry step of the SARS-CoV-2 lifecycle. These results justify that a proof-of-concept Phase 2 trial be rapidly conducted with alisporivir in patients with SARS-CoV-2 infection.
Accepted Manuscript Posted 6 May 2020, AAC; Final Article Posted 23 June 2020
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Research Article
Design of potent membrane fusion inhibitors against SARS-CoV-2, an emerging coronavirus with high fusogenic activity
The COVID-19 pandemic caused by SARS-CoV-2 presents a serious global public health emergency in urgent need of prophylactic and therapeutic interventions. The S protein of coronaviruses mediates viral receptor-binding and membrane fusion thus being considered a critical target for antivirals. Herein, we report that the SARS-CoV-2 S protein evolves a high activity to mediate cell-cell fusion, significantly differing from the S protein of the previously emerged SARS-CoV. In comparison, the HR1 sequence in the fusion protein of SARS-CoV-2 adopts a much higher helical stability and can interact with the HR2 site to form a six-helical bundle structure more efficiently, underlying the mechanism of the enhanced fusion capacity. Also importantly, the design of membrane fusion inhibitors with high potencies against both SARS-CoV-2 and SARS-CoV has provided potential arsenals to combat the pandemic and tools to exploit the fusion mechanism.
Accepted Manuscript Posted 6 May 2020, JVI; Final Article Posted 1 July 2020
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Observation
An Extensive Meta-Metagenomic Search Identifies SARS-CoV-2-Homologous Sequences in Pangolin Lung Viromes
Meta-metagenomic searches allow for high-speed, low-cost identification of potentially significant biological niches for sequences of interest.
6 May 2020, mSphere
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Observation
SARS-CoV-2 and ORF3a: Nonsynonymous Mutations, Functional Domains, and Viral Pathogenesis
At the surge of the coronavirus disease 2019 (COVID-19) pandemic, we detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. Our analysis showed that the functional domains were linked to virulence, infectivity, ion channel formation, and virus release in SARS-CoV-2 3a. Our study also revealed the functional importance of conserved domains across the species barrier. Observations reported in this study merit experimental confirmation.
5 May 2020, mSystems
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Research Article
Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs
Drug repositioning is the only feasible option to address the COVID-19 global challenge immediately. We screened a panel of 48 FDA-approved drugs against SARS-CoV-2 which were pre-selected by an assay of SARS-CoV and identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low micromolar IC50s and in particular, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects.
Accepted Manuscript Posted 4 May 2020, AAC; Final Article Posted 23 June 2020
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Research Article
Multicenter Evaluation of the Cepheid Xpert Xpress SARS-CoV-2 Test
Nucleic acid amplification tests (NAATs) are the primary means of identifying acute infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Accurate and fast test results may permit more efficient use of protective and isolation resources and allow for rapid therapeutic interventions.
Accepted Manuscript Posted 4 May 2020, JCM; Final Article Posted 23 July 2020
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Letter to the Editor
An 81 nucleotide deletion in SARS-CoV-2 ORF7a identified from sentinel surveillance in Arizona (Jan-Mar 2020)
On January 26 2020, the first Coronavirus Disease 2019 (COVID-19) case was reported in Arizona (3rd case in the US) (1)....
Accepted Manuscript Posted 1 May 2020, JVI; Final Article Posted 1 July 2020
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Commentary
The Role of Antibody Testing for SARS-CoV-2: Is There One?
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) brought with it rapid development of both molecular and serologic assays for identification of COVID-19 infections. While Food and Drug Administration (FDA) emergency use authorization (EUA) is required for clinical application of SARS-CoV-2 molecular tests, submission for EUA is currently a voluntary process for manufacturers of serologic assays. The absence of FDA oversight of serologic tests is concerning, given that the commercially available serologic assays are highly variable, differing in their format, the antibody class detected, the targeted antigen and the acceptable specimen types. An added complication is the lack of a clear understanding for how such assays should be utilized and what the reported results ultimately indicate, or perhaps more importantly, what they do not indicate. Here, we provide a brief summary of the performance of a number of serologic assays reported in the literature, comment on what we do and do not know regarding our immune response to SARS-CoV-2, and provide a number of scenarios for which serologic testing will play a role in during our global response to this pandemic.
Accepted Manuscript Posted 29 April 2020, JCM; Final Article Posted 23 July 2020