COVID 19 Special Collection
COVID-19 (SARS-CoV-2) Special Collection
Latest COVID-19 Articles
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Research Article
SARS-CoV-2 and three related coronaviruses utilize multiple ACE2 orthologs and are potently blocked by an improved ACE2-Ig
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the currently uncontrolled coronavirus disease 2019 (COVID-19) pandemic. It is important to study the host range of SARS-CoV-2 because some domestic species might harbor the virus and transmit it back to humans. In addition, insight into the ability of SARS-CoV-2 and SARS-like viruses to utilize animal orthologs of the SARS-CoV-2 receptor ACE2 might provide structural insight into improving ACE2-based viral entry inhibitors. In this study, we found that ACE2 orthologs of a wide range of domestic and wild animals can support cell entry of SARS-CoV-2 and three related coronaviruses, providing insights into identifying animal hosts of these viruses. We also developed recombinant ACE2-Ig proteins that are able to potently block these viral infections, providing a promising approach to developing antiviral proteins broadly effective against these distinct coronaviruses.
Accepted Manuscript Posted 26 August 2020, JVI
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Research Article
Development and Clinical Application of a Rapid and Sensitive Loop-Mediated Isothermal Amplification Test for SARS-CoV-2 Infection
We developed a visual and rapid reverse transcription–loop-mediated isothermal amplification (RT-LAMP) assay targeting the S gene for SARS-CoV-2 infection. The strength of our study was that we validated the RT-LAMP assay using 481 clinical respiratory samples from two prospective cohorts of suspected COVID-19 patients and on the serial samples from an asymptomatic carrier. The developed RT-LAMP approach showed an increased sensitivity (88.89%) and high consistency (kappa, 0.92) compared with those of reverse transcription-quantitative PCR (RT-qPCR) for SARS-CoV-2 screening while requiring only constant-temperature heating and visual inspection, facilitating SARS-CoV-2 screening in well-equipped labs as well as in the field. The time required for RT-LAMP was less than 1 h from sample preparation to the result (more than 2 h for RT-qPCR). This study showed that the RT-LAMP assay was a simple, rapid, and sensitive approach for SARS-CoV-2 infection and can facilitate COVID-19 diagnosis, especially in resource-poor settings.
26 August 2020, mSphere
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Commentary
Evaluation of High Throughput Serological Tests for SARS-CoV-2
Serologic methods are an important part of a clinical laboratory's portfolio of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests and are essential to the broader response to coronavirus infectious disease 2019 (COVID-19) including epidemiological studies and vaccine development. There are currently a number of commercial SARS-CoV-2 antibody tests with Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration. In this issue of the Journal of Clinical Microbiology, H. E. Prince et al. (J Clin Microbiol 58:e01742-20, https://doi.org/10.1128/JCM.01742-20) report the results of their evaluation of the agreement of 4 high throughput EUA tests for SARS-CoV-2 IgG: Abbott Architect, Diasorin Liaison, Euroimmun, and Ortho VITROS. They showed excellent agreement between the tests, and rare false-positive reactivity for all tests.
Accepted Manuscript Posted 25 August 2020, JCM; Final Article Posted 21 October 2020
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Editorial
Can We Test Our Way Out of the COVID-19 Pandemic?
Frequent, low cost, universal testing for SARS-CoV-2 with quarantine of those with a positive result has been suggested as a strategy to address the COVID-19 pandemic in the United States. Specifically, home or community use of test that use paper-strip detection devices, which may have reduced sensitivity for SARS-CoV-2, has been advocated. There are several potential challenges or problems with this strategy, including the availability of such tests, consequences of incorrect test results, difficulties with adherence to testing, and the accuracy of such tests for detection of infectious people. Because of these, we think it is premature to strongly advocate for such a testing strategy, as the adverse consequences may outweigh any benefits. High-quality outcomes data demonstrating the efficacy of this testing strategy are needed before widespread implementation.
Accepted Manuscript Posted 25 August 2020, JCM; Final Article Posted 21 October 2020
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Research Article
Inactivation analysis of SARS-CoV-2 by specimen transport media, nucleic acid extraction reagents, detergents and fixatives
The COVID-19 pandemic has necessitated a multi-faceted rapid response by the scientific community, bringing researchers, health officials and industry together to address the ongoing public health emergency. To meet this challenge, participants need an informed approach for working safely with the etiological agent, the novel human coronavirus SARS-CoV-2. Work with infectious SARS-CoV-2 is currently restricted to high-containment laboratories, but material can be handled at a lower containment level after inactivation. Given the wide array of inactivation reagents that are being used in laboratories during this pandemic, it is vital that their effectiveness is thoroughly investigated. Here, we evaluated a total of 23 commercial reagents designed for clinical sample transportation, nucleic acid extraction and virus inactivation for their ability to inactivate SARS-CoV-2, as well as seven other common chemicals including detergents and fixatives. As part of this study, we have also tested five filtration matrices for their effectiveness at removing the cytotoxic elements of each reagent, permitting accurate determination of levels of infectious virus remaining following treatment. In addition to providing critical data informing inactivation methods and risk assessments for diagnostic and research laboratories working with SARS-CoV-2, these data provide a framework for other laboratories to validate their inactivation processes and to guide similar studies for other pathogens.
Accepted Manuscript Posted 24 August 2020, JCM; Final Article Posted 21 October 2020
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Research Article
Neutralizing antibodies correlate with protection from SARS-CoV-2 in humans during a fishery vessel outbreak with high attack rate
The development of vaccines against SARS-CoV-2 would be greatly facilitated by the identification of immunological correlates of protection in humans. However, to date, studies on protective immunity have only been performed in animal models and correlates of protection have not been established in humans. Here, we describe an outbreak of SARS-CoV-2 on a fishing vessel associated with a high attack rate. Predeparture serological and viral RT-PCR testing along with repeat testing after return to shore was available for 120 of the 122 persons on board over a median follow-up of 32.5 days (range 18.8 to 50.5 days). A total of 104 individuals had an RT-PCR positive viral test with Ct <35 or seroconverted during the follow-up period, yielding an attack rate on board of 85.2% (104/122 individuals). Metagenomic sequencing of 39 viral genomes suggested the outbreak originated largely from a single viral clade. Only three crewmembers tested seropositive prior to the boat's departure in initial serological screening and also had neutralizing and spike-reactive antibodies in follow-up assays. None of these crewmembers with neutralizing antibody titers showed evidence of bona fide viral infection or experienced any symptoms during the viral outbreak. Therefore, the presence of neutralizing antibodies from prior infection was significantly associated with protection against re-infection (Fisher's exact test, p=0.002).
Accepted Manuscript Posted 21 August 2020, JCM; Final Article Posted 21 October 2020
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Research Article
GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection
Targeting the main protease (Mpro) of SARS-CoV-2, we identified two indole-chloropyridinyl-ester derivatives, GRL-0820 and GRL-0920, active against SARS-CoV-2, employing RNA-qPCR and immunocytochemistry and show that the two compounds exerted potent activity against SARS-CoV-2. While GRL-0820 and remdesivir blocked SARS-CoV-2 infection, viral breakthrough occurred as examined with immunocytochemistry. In contrast, GRL-0920 completely blocked the infectivity and cytopathic effect of SARS-CoV-2 without significant toxicity. Structural modeling showed that indole and chloropyridinyl of the derivatives interacted with two catalytic dyad residues of Mpro, Cys145 and His41, resulting in covalent bonding, which was verified using HPLC/MS. The present data should shed light on the development of therapeutics for COVID-19, and optimization of GRL-0920 based on the present data is essential to develop more-potent anti-SARS-CoV-2 compounds for treating COVID-19.
20 August 2020, mBio
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Research Article
Antibiotic consumption and stewardship at a hospital outside of an early Coronavirus disease 2019 epicentre
There are scant data on impact of coronavirus disease (COVID)-19 on hospital antibiotic consumption, and no data from outside epicentres. At our non-epicentre hospital, antibiotic days of therapy (DOT) and bed days of care (BDOC) were reduced by 151.5/month and 285/month, respectively, for March-June 2020, compared to 2018-19 (P=0.001 and P<0.001). DOT/1,000 BDOC was increased (8.1/month, P=0.001). COVID-19 will impact antibiotic consumption, stewardship and resistance in ways that will likely differ temporally and by region.
Accepted Manuscript Posted 19 August 2020, AAC; Final Article Posted 20 October 2020
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Research Article
Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo
There are no FDA approved antivirals for any coronavirus, including SARS-CoV-2. Numerous drugs are already approved for human use that may have antiviral activity and therefore could potentially be rapidly re-purposed as antivirals. Here, we present data assessing the antiviral activity of 20 FDA approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV in vitro. We find 17 of these inhibit SARS-CoV-2, suggesting these may have pan-anti-coronaviral activity. We directly follow-up with seven of these and find they all inhibit infectious SARS-CoV-2 production. Moreover, we have evaluated chloroquine and chlorpromazine in vivo using mouse-adapted SARS-CoV. We find neither drug inhibited viral replication in the lungs, but both protected against clinical disease.
Accepted Manuscript Posted 19 August 2020, JVI; Final Article Posted 14 October 2020
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Research Article
Persistence of Bacteriophage Phi 6 on Porous and Nonporous Surfaces and the Potential for Its Use as an Ebola Virus or Coronavirus Surrogate
Understanding the persistence of enveloped viruses helps inform infection control practices and procedures in health care facilities and community settings. These data convey to public health investigators that enveloped viruses can persist and remain infective on surfaces, thus demonstrating a potential risk for transmission. Under these laboratory-simulated Western indoor hospital conditions, we assessed the suitability of phi 6 as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses.
18 August 2020, AEM
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Research Article
Detection of SARS-CoV-2 IgG Targeting Nucleocapsid or Spike Protein by Four High Throughput Immunoassays Authorized for Emergency Use
A total of 1200 serum samples that were tested for SARS-CoV-2 IgG antibody using the Abbott Architect immunoassay targeting the nucleocapsid protein were run in 3 SARS-CoV-2 IgG immunoassays targeting spike proteins (DiaSorin Liaison, Ortho VITROS, and Euroimmun). Consensus-positive and consensus-negative interpretations were defined as qualitative agreement in at least 3 of the 4 assays. Agreement of the 4 individual assays with a consensus-negative interpretation (N=610) ranged from 96.7% to 100%, and agreement with a consensus-positive interpretation (N=584) ranged from 94.3% to 100%. Laboratory-developed inhibition assays were utilized to evaluate 49 consensus-negative samples positive in only one assay; true-positive reactivity was confirmed in only 2 of these 49 (4%) samples. These findings demonstrate very high levels of agreement among 4 SARS-CoV-2 IgG assays authorized for emergency use, regardless of antigen target or assay format. Although false-positive reactivity was identified, its occurrence was rare (no more than 1.7% of samples for a given assay).
Accepted Manuscript Posted 18 August 2020, JCM; Final Article Posted 21 October 2020
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Research Article
Oscillatory Dynamics in Infectivity and Death Rates of COVID-19
The infectivity and death rates for COVID-19 have been observed in many countries around the world as well as in the collective data of the whole world. These oscillations show distinct circaseptan periodicity, which could be associated with numerous biological reasons as well as with improper reporting of the data collected. Since very different results are observed in different countries and even continents, such as Sweden (very significant oscillations) or India (almost no oscillations), these data provide a very important message about different conditions under which the disease is spread or is reported, which, in turn, could serve as guidance tools in future epidemics. It is necessary that follow-up studies track the observed differences and fully reliably address their origins.
18 August 2020, mSystems
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Review
Convalescent Plasma Therapy for COVID-19: State of the Art
Convalescent plasma (CP) therapy has been used since the early 1900s to treat emerging infectious diseases; its efficacy was later associated with the evidence that polyclonal neutralizing antibodies can reduce the duration of viremia. Recent large outbreaks of viral diseases for which effective antivirals or vaccines are still lacking has renewed the interest in CP as a life-saving treatment. The ongoing COVID-19 pandemic has led to the scaling up of CP therapy to unprecedented levels. Compared with historical usage, pathogen reduction technologies have now added an extra layer of safety to the use of CP, and new manufacturing approaches are being explored. This review summarizes historical settings of application, with a focus on betacoronaviruses, and surveys current approaches for donor selection and CP collection, pooling technologies, pathogen inactivation systems, and banking of CP. We additionally list the ongoing registered clinical trials for CP throughout the world and discuss the trial results published thus far.
12 August 2020, CMR
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Research Article
Low-Cost Polyester-Tipped 3-Dimensionally-Printed Nasopharyngeal Swab for the Diagnosis of Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2)
Case identification, isolation and contact tracing are fundamental strategies used to control the spread of Coronavirus Disease 2019 (COVID-19). This has led to widespread testing that resulted in the interruption of the supply chain for testing materials around the world. A prospective study was conducted to compare cheap and easily sourced 3-dimensionally printed polylactic acid and polyester nasopharyngeal swabs to commercially manufactured swabs, in detecting severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). During the study period, 287 laboratory-confirmed hospitalized COVID-19 patients, at multiple stages of their illness, were enrolled. The median age for the study population was 47.6 years (IQR: 34.4-56.6 years) and two-thirds (67.6%) of the subjects were male. The median duration of hospitalization, at the time of sampling, was 13 days (IQR 10-16 days). Overall concordance between the prototype and control swabs was 80.8% (Cohen's kappa coefficient = 0.61). Most discrepant results were due to prototype-positive control-negative results. When considering all positive results to be true positives, the prototype swab had a higher sensitivity (90.6% vs 80.8%, 95%CI 85.7-94.0% and 74.7-85.7%, respectively, p < 0.015). The cost to produce the prototype swab was estimated to be 0.05 USD per swab. Polylactic acid 3D-printed polyester-tipped swabs were shown to be effective for nasopharyngeal sample collection. We believe that this design can easily be adopted in countries where commercial swabs are not readily available and can play a vital role in public health efforts for disease control in low-income countries.
Accepted Manuscript Posted 12 August 2020, JCM; Final Article Posted 21 October 2020
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Commentary
Challenges and Controversies Related to Testing for COVID-19
The coronavirus disease (COVID)-19 pandemic has placed the clinical laboratory and testing for SARS-CoV-2 front-and-center in the worldwide discussion of how to end the outbreak. Clinical laboratories have responded by developing, validating and implementing a variety of molecular and serologic assays to test for SARS-CoV-2 infection. This has played an essential role in identifying cases, informing isolation decisions and helping to curb the spread of disease. However, as the demand for COVID-19 testing has increased, laboratory professionals have faced a growing list of challenges, uncertainties and, in some situations, controversy, as they have attempted to balance the need for increasing test capacity with maintaining a high-quality laboratory operation. The emergence of this new viral pathogen has raised unique diagnostic questions for which there have not always been straightforward answers. In this commentary, the author addresses several areas of current debate, including 1) the role of molecular assays in defining the duration of isolation/quarantine, 2) whether the PCR cycle threshold value should be included on patient reports, 3) if specimen pooling and testing by research staff represent acceptable solutions to expand screening, and 4) whether testing a large percentage of the population is feasible and represents a viable strategy to end the pandemic.
Accepted Manuscript Posted 12 August 2020, JCM; Final Article Posted 21 October 2020