COVID 19 Special Collection
COVID-19 (SARS-CoV-2) Special Collection
Latest COVID-19 Articles
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Opinion/Hypothesis
COVID-19 Hyperinflammation: What about Neutrophils?
COVID-19 is often related to hyperinflammation that drives lung or multiorgan injury. The immunopathological mechanisms that cause excessive inflammation are under investigation and constantly updated. Here, a gene network approach was used on recently published data sets to identify possible COVID-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-CoV-2 cellular receptors led to the mining of a neutrophil-response signature and relevant inflammatory genes. Second, analysis of RNA-seq data sets of lung cells infected with SARS-CoV-2 revealed that infected cells expressed neutrophil-attracting chemokines. Third, analysis of RNA-seq data sets of bronchoalveolar lavage fluid cells from COVID-19 patients identified upregulation of neutrophil genes and chemokines. Different inflammatory genes mined here, including TNFR, IL-8, CXCR1, CXCR2, ADAM10, GPR84, MME, ANPEP, and LAP3, might be druggable targets in efforts to limit SARS-CoV-2 inflammation in severe clinical cases. The possible role of neutrophils in COVID-19 inflammation needs to be studied further.
24 June 2020, mSphere
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Research Article
Rampant C→U Hypermutation in the Genomes of SARS-CoV-2 and Other Coronaviruses: Causes and Consequences for Their Short- and Long-Term Evolutionary Trajectories
The wealth of accurately curated sequence data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its long genome, and its low substitution rate provides a relatively blank canvas with which to investigate effects of mutational and editing processes imposed by the host cell. The finding that a large proportion of sequence change in SARS-CoV-2 in the initial months of the pandemic comprised C→U mutations in a host APOBEC-like context provides evidence for a potent host-driven antiviral editing mechanism against coronaviruses more often associated with antiretroviral defense. In evolutionary terms, the contribution of biased, convergent, and context-dependent mutations to sequence change in SARS-CoV-2 is substantial, and these processes are not incorporated by standard models used in molecular epidemiology investigations.
24 June 2020, mSphere
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Observation
Asymptomatic COVID-19 Patients Can Contaminate Their Surroundings: an Environment Sampling Study
Although it has been well recognized that the virus SARS-CoV-2, the causative agent of COVID-19, can be acquired by exposure to fomites, surprisingly, the contamination of patients’ surroundings by SARS-CoV-2 is largely unknown, as there have been few studies. We performed an environmental sampling study for 13 laboratory-confirmed COVID-19 patients and found extensive contamination of patients’ surroundings. In particular, we found that asymptomatic COVID-19 patients contaminated their surroundings and therefore imposed risks for other people. Environment cleaning should be emphasized in negative-pressure rooms. The findings may be useful to guide infection control practice to protect health care workers.
24 June 2020, mSphere
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Research Article
IMPACT OF GLUCOCORTICOID TREATMENT IN SARS-COV-2 INFECTION MORTALITY: A RETROSPECTIVE CONTROLLED COHORT STUDY
Evidence to support the use of steroids in COVID-19 pneumonia is lacking. We aim to determine the impact of steroid use in COVID-19 pneumonia in-hospital mortality. We performed a single-center retrospective cohort study in a University hospital in Madrid, Spain, during March 2020. To determine the role of steroids in in-hospital mortality, patients admitted with SARS-CoV-2 pneumonia and treated with steroids were compared to patients not treated with steroids, adjusting by a propensity-score for steroid treatment. Survival times were compared using log-rank test. Different steroid regimens were compared, and adjusted with a second propensity score.
Accepted Manuscript Posted 22 June 2020, AAC; Final Article Posted 20 August 2020
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Research Article
Analytical and Clinical Comparison of Three Nucleic Acid Amplification Tests for SARS-CoV-2 Detection
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first identified in December 2019 and has quickly become a worldwide pandemic. In response, many diagnostic manufacturers have developed molecular assays for SARS-CoV-2 under the Food and Drug Administration (FDA) Emergency Use Authorization (EUA) pathway. This study compared 3 of these assays: the Hologic Panther Fusion SARS-CoV-2 assay (Fusion), the Hologic Aptima SARS-CoV-2 assay (Aptima) and the BioFire Defense COVID-19 test (BioFire), to determine analytical and clinical performance, as well as workflow. All 3 assays showed a similar limit of detection (LOD) using inactivated virus, with 100% detection ranging from 500-1,000 genome equivalents/ml, whereas use of a quantified RNA transcript standard showed the same trend, but had values ranging from 62.5 to 125 copies/ml, confirming variability in absolute quantification of reference standards. The clinical correlation found that the Fusion and BioFire assays had a positive percent agreement (PPA) of 98.7%, followed by the Aptima assay at 94.7% when compared to the consensus result. All three assays exhibited 100% negative percent agreement (NPA). Analysis of discordant results revealed that all 4 samples missed by the Aptima assay had Ct values >37 on the Fusion assay. In conclusion, while all three assays showed similar relative LODs, we showed differences in absolute LODs depending on which standard was employed. In addition, the Fusion and BioFire assays showed better clinical performance, while the Aptima assay showed a modest decrease in overall PPA. These findings should be kept in mind when making platform testing decisions.
Accepted Manuscript Posted 22 June 2020, JCM; Final Article Posted 24 August 2020
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Research Article
Identification of common deletions in the spike protein of SARS-CoV-2
The spike protein determines the infectivity and host range of coronaviruses. SARS-CoV-2 has two unique features in its spike protein, the receptor binding domain and an insertion of twelve nucleotides at the S1/S2 boundary resulting a furin-like cleavage site. Here, we identified two deletion variants of SARS-CoV-2 that either directly affect the furin-like cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN) and investigated these deletions in cell isolates and clinical samples. The absence of the polybasic cleavage site in SARS-CoV-2 did not affect virus replication in Vero or Vero-E6 cells. Our data indicate the PRRAR and its flanking sites are not fixed in vitro, thus there appears to be distinct selection pressures on SARS-CoV-2 sequences in vitro and in vivo. Further investigation of the mechanism of generating these deletion variants and their infectivity in different animal models would improve our understanding of the origin and evolution of this virus.
Accepted Manuscript Posted 22 June 2020, JVI; Final Article Posted 17 August 2020
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Opinion/Hypothesis
Could an Unrelated Live Attenuated Vaccine Serve as a Preventive Measure To Dampen Septic Inflammation Associated with COVID-19 Infection?
We propose the concept that administration of an unrelated live attenuated vaccine, such as MMR (measles, mumps, rubella), could serve as a preventive measure against the worst sequelae of coronavirus disease 2019 (COVID-19). There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing “trained” nonspecific innate immune cells for improved host responses against subsequent infections. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19. Following the lead of other countries conducting clinical trials with the live attenuated Mycobacterium bovis BCG (BCG) vaccine under a similar concept, a clinical trial with MMR in high-risk populations may provide a “low-risk–high-reward” preventive measure in saving lives during this unprecedented COVID-19 pandemic.
19 June 2020, mBio
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Letter to the Editor
When to re-test: An examination of repeat COVID PCR patterns in an ambulatory population
Healthcare facilities have limited supplies for SARS-CoV-2 amplification/detection, putting them under pressure to optimize reagent use.…
Accepted Manuscript Posted 17 June 2020, JCM; Final Article Posted 24 August 2020
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Letter to the Editor
The Nucleocapsid Protein of SARS–CoV-2: a Target for Vaccine Development
During the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2), there has been an unprecedented level of global collaboration that has led to a rapid characterization of SARS–CoV-2.…
16 June 2020, JVI
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Letter to the Editor
Protections against the Risk of Airborne SARS-CoV-2 Infection
Dietz at al. (1) call attention to issues that affect the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the built environment.…
16 June 2020, mSystems
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Author Reply
Reply to McDonald, “Protections against the Risk of Airborne SARS-CoV-2 Infection”
We thank Dr. McDonald (1) for his close reading of our paper (2) and acknowledge that he makes important arguments for exercising precautions in order to prevent built environment-mediated transmission of SARS-CoV-2.…
16 June 2020, mSystems
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Genome Sequences
Complete Genome Sequence of a Novel Coronavirus (SARS-CoV-2) Isolate from Bangladesh
The complete genome sequence of a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) isolate obtained from a nasopharyngeal swab from a patient with COVID-19 in Bangladesh is reported.
11 June 2020, MRA
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Minireview
Comparative pathogenesis of bovine and porcine respiratory coronaviruses in the animal host species and SARS-CoV-2 in humans
Discovery of bats with severe acute respiratory syndrome (SARS)-related coronaviruses (CoVs) raised the spector of potential future outbreaks of zoonotic SARS-CoV-like disease in humans, which largely went unheeded. Nevertheless, the novel SARS-CoV-2 of bat ancestoral origin emerged to infect humans in Wuhan, China in late 2019 and then became a global pandemic. Less than 5 months after its emergence, millions of people worldwide have been infected asymptomatically or symptomatically and at least 360,000 have died. Coronavirus disease 2019 (COVID-19) in severely affected patients includes atypical pneumonia characterized by a dry cough, persistent fever, and progressive dyspnea and hypoxia, sometimes accompanied by diarrhea and often followed by multiple organ failure, especially, the respiratory and cardiovascular systems. In this mini-review, we focus on two endemic respiratory CoV infections of livestock: Bovine coronavirus (BCoV) and porcine respiratory coronavirus (PRCV). Both animal respiratory CoVs share some common features with SARS-CoV and SARS-CoV-2. BCoV has a broad host range including wild ruminants and a zoonotic potential. BCoV also has a dual tropism for the respiratory and gastrointestinal tracts. These aspects, their interspecies transmission and certain factors that impact disease severity in cattle parallel related facets of SARS-CoV or SARS-CoV-2 in humans. PRCV has a tissue tropism for the upper and lower respiratory tracts and a cellular tropism for type 1 and 2 pneumocytes in lung, but is generally a mild infection unless complicated by other exacerbating factors, such as bacterial or viral co-infections and immunosuppression (corticosteroids).
Accepted Manuscript Posted 10 June 2020, JCM; Final Article Posted 23 July 2020
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Research Article
Culture-based virus isolation to evaluate potential infectivity of clinical specimens tested for COVID-19
Real-time reverse transcription (RT)-PCR is currently the most sensitive method to detect severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, the correlation between detectable viral RNA and culturable virus in clinical specimens remains unclear. Here, we performed virus culture for 60 specimens that were confirmed to be positive for SARS-CoV-2 RNA by real-time RT-PCR. The virus could be successfully isolated from 12 throat and nine nasopharyngeal swabs, and two from sputum specimens. The lowest copy number required for virus isolation was determined to be 5.4, 6.0, and 5.7 log10 genome copies/mL sample for detecting the nsp12, E, and N gene, respectively. We further examined the correlation of genome copy number and virus isolation in different regions of the viral genome, demonstrating that culturable specimens are characterized by high copy numbers with a linear correlation observed between copy numbers of amplicons targeting structural and non-structural regions. Overall, these results indicate that in addition to the copy number, the integrity of the viral genome should be considered when evaluating the infectivity of clinical SARS-CoV-2 specimens.
Accepted Manuscript Posted 9 June 2020, JCM; Final Article Posted 23 July 2020
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Research Article
Evaluation of COVID-19 IgG/IgM Rapid Test from Orient Gene Biotech
While the COVID-19 pandemic has peaked in many countries already, the current challenge is to assess population immunity on large scale. Many serological tests are available and require urgent independent validation. Here we report performance characteristics of Orient Gene (OG) COVID-19 IgG/IgM Rapid Test Cassette compare it Abbott SARS-CoV-2 IgG immunoassay (ASIA). Patients (n=102) with a positive SARS-CoV-2 RT-PCR were tested. They were asymptomatic (n=2), had mild (n=37) or severe symptoms requiring hospitalization in medical (n=35) or intensive care unit (n=28). Specificity was evaluated on 42 patients with previous viral and parasitic diseases as well as high level of rheumatic factor. Sensitivity of OG was 95.8% (CI95% 89.6-98.8) for samples collected ≥10 days after onset of symptoms which was equivalent to sensitivity of ASIA of 90.5% (IC95% 82.8-95.6). OG uncovered 6 false negative of ASIA, of which two had only IgM with OG. Specificity was 100% (CI95% 93.4-100) with both tests on samples including patients infected with endemic coronavirus. Overall, OG performance characteristics indicate that the test is suitable for routine use in clinical laboratories and performance is equivalent to immunoassay. Testing OG on a larger asymptomatic population may be needed to confirm these results.
Accepted Manuscript Posted 9 June 2020, JCM; Final Article Posted 23 July 2020