COVID 19 Special Collection
COVID-19 (SARS-CoV-2) Special Collection
Latest COVID-19 Articles
-
Brief Case
The Brief Case: “Not Positive” or “Not Sure”—COVID-19-Negative Results in a Symptomatic Patient
A previously healthy 35-year-old male presented to our hospital in mid-March 2020 with an acute subarachnoid hemorrhage (SAH)....
23 July 2020, JCM
-
Brief Case
Closing the Brief Case: “Not Positive” or “Not Sure”—COVID-19-Negative Results in a Symptomatic Patient
Which of the following best describes potential reasons for false-negative molecular testing for SARS-CoV-2?...
23 July 2020, JCM
-
Commentary
The COVID-19 Diagnostic Dilemma: a Clinician's Perspective
In this commentary, we provide a broad overview of how the rapidly evolving coronavirus disease 2019 (COVID-19) diagnostic landscape has impacted clinical care during the COVID-19 pandemic. We review aspects of both molecular and serologic testing and discuss the logistical challenges faced with each. We also highlight the progress that has been made in the development and implementation of these assays as well as the need for ongoing improvement in diagnostic testing capabilities.
23 July 2020, JCM
-
Editorial
Special Issue on Diagnostic Testing for Severe Acute Respiratory Syndrome Coronavirus 2 and Lessons from This Pandemic
As I write this, near the end of May 2020, there have been over 5.8 million cases of confirmed coronavirus disease 2019 (COVID-19) worldwide, with over 1.7 million cases in the United States....
23 July 2020, JCM
-
Commentary
The First Quarter of SARS-CoV-2 Testing: the University of Washington Medicine Experience
In early March 2020, the University of Washington Medical Center clinical virology laboratory became one of the first clinical laboratories to offer testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). When we first began test development in mid-January, neither of us believed there would be more than 2 million confirmed SARS-CoV-2 infections nationwide or that we would have performed more than 150,000 real-time PCR (RT-PCR) tests, with many more to come. This article will be a chronological summary of how we rapidly validated tests for SARS-CoV-2, increased our testing capacity, and addressed the many problems that came up along the way.
23 July 2020, JCM
-
Research Article
Saliva sampling and its direct lysis, an excellent option to increase the number of SARS CoV2 diagnostic tests in settings with supply shortages
As part of any plan to lift or ease the confinement restrictions that are in place in many different countries, there is an urgent need to increase the capacity of laboratory testing for SARS CoV-2. Detection of the viral genome through RT-qPCR is the golden standard for this test, however, the high demand of the materials and reagents needed to sample individuals, purify the viral RNA, and perform the RT-qPCR test has resulted in a worldwide shortage of several of these supplies. Here, we show that directly lysed saliva samples can serve as a suitable source for viral RNA detection that is cheaper and can be as efficient as the classical protocol that involves column purification of the viral RNA. In addition, it surpasses the need for swab sampling, decreases the risk of the healthcare personnel involved in this process, and accelerates the diagnostic procedure.
Accepted Manuscript Posted 23 July 2020, JCM; Final Article Posted 22 September 2020
-
Observation
Can Dietary Fatty Acids Affect the COVID-19 Infection Outcome in Vulnerable Populations?
There is high mortality in coronavirus disease 2019 (COVID-19)-infected individuals with chronic inflammatory diseases, like obesity, diabetes, and hypertension. A cytokine storm in some patients after infection contributes to this mortality. In addition to lungs, the intestine is targeted during COVID-19 infection. The intestinal membrane serves as a barrier to prevent leakage of microorganisms and their products into the bloodstream; however, dietary fats can affect the gut microbiome and may increase intestinal permeability. In obese or diabetic individuals, there is an increase in the abundance of either Gram-negative bacteria in the gut or their product, endotoxin, in systemic circulation. We speculate that when the COVID-19 infection localizes in the intestine and when the permeability properties of the intestinal membrane are compromised, an inflammatory response is generated when proinflammatory endotoxin, produced by resident Gram-negative bacteria, leaks into the systemic circulation. This review discusses conditions contributing to inflammation that are triggered by microbially derived factors from the gut.
23 July 2020, mBio
-
Research Article
Evolutionary arms race between virus and host drives genetic diversity in bat SARS related coronavirus spike genes
Evolutionary arms race dynamics shape the diversity of viruses and their receptors. Identification of key residues which are involved in interspecies transmission is important to predict potential pathogen spillover from wildlife to humans. Previously, we have identified genetically diverse SARSr-CoV in Chinese horseshoe bats. Here, we show the highly polymorphic ACE2 in Chinese horseshoe bat populations. These ACE2 variants support SARS- and SARSr-CoV infection but with different binding affinity to different spike proteins. The higher binding affinity of SARSr-CoV spike to human ACE2 suggests that these viruses have the capacity of spillover to humans. The positive selection of residues at the interface between ACE2 and SARSr-CoV spike protein suggests a long-term and ongoing coevolutionary dynamics between them. Continued surveillance of this group of viruses in bats is necessary for the prevention of the next SARS-like disease.
Accepted Manuscript Posted 22 July 2020, JVI; Final Article Posted 29 September 2020
-
Research Article
Type I and Type III IFN Restrict SARS-CoV-2 Infection of Human Airway Epithelial Cultures
The current pandemic of respiratory illness, COVID-19, is caused by a recently emerged coronavirus named SARS-CoV-2. This virus infects airway and lung cells causing fever, dry cough, and shortness of breath. Severe cases of COVID-19 can result in lung damage, low blood oxygen levels, and even death. As there are currently no vaccines approved for use in humans, studies of the mechanisms of SARS-CoV-2 infection are urgently needed. Our research identifies an excellent system to model SARS-CoV-2 infection of the human airways, that can be used to test various treatments. Analysis of infection in this model system found that human airway epithelial cultures induce a strong pro-inflammatory cytokine response yet block the production of type I and III IFNs. to SARS-CoV-2. However, treatment of airway cultures with the immune molecules, type I or type III interferon (IFN) was able to inhibit SARS-CoV-2 infection. Thus, our model system identified type I or type III IFN as potential antiviral treatments for COVID-19 patients.
Accepted Manuscript Posted 22 July 2020, JVI; Final Article Posted 15 September 2020
-
Research Article
Discovery and Genomic Characterization of a 382-Nucleotide Deletion in ORF7b and ORF8 during the Early Evolution of SARS-CoV-2
During the SARS epidemic in 2003/2004, a number of deletions were observed in ORF8 of SARS-CoV, and eventually deletion variants became predominant, leading to the hypothesis that ORF8 was an evolutionary hot spot for adaptation of SARS-CoV to humans. However, due to the successful control of the SARS epidemic, the importance of these deletions for the epidemiological fitness of SARS-CoV in humans could not be established. The emergence of multiple SARS-CoV-2 strains with ORF8 deletions, combined with evidence of a robust immune response to ORF8, suggests that the lack of ORF8 may assist with host immune evasion. In addition to providing a key insight into the evolutionary behavior of SARS-CoV-2 as the virus adapts to its new human hosts, the emergence of ORF8 deletion variants may also impact vaccination strategies.
21 July 2020, mBio
-
Perspective
COVID-19 and the Gut Microbiome: More than a Gut Feeling
Due to its fundamental role in the induction, training, and function of the immune system, it is critical to include characterizations of the gut microbiome in clinical trials and studies that aim to broaden our understanding of coronavirus disease 2019 (COVID-19). Understanding the “gut-lung axes,” where gut microbiome composition influences the lung’s susceptibility to viral infections and viral infections of the lung alter gut microbiome composition toward proinflammatory functional dysbiosis, will be critical in addressing COVID-19, including disease progression, the importance of preexisting conditions, and the risk for developing complications. These insights may further help to develop better intervention strategies for COVID-19 and other diseases caused by respiratory viruses.
21 July 2020, mSystems
-
Research Article
SARS-CoV-2 Titers in Wastewater Are Higher than Expected from Clinically Confirmed Cases
Wastewater-based surveillance is a promising approach for proactive outbreak monitoring. SARS-CoV-2 is shed in stool early in the clinical course and infects a large asymptomatic population, making it an ideal target for wastewater-based monitoring. In this study, we develop a laboratory protocol to quantify viral titers in raw sewage via qPCR analysis and validate results with sequencing analysis. Our results suggest that the number of positive cases estimated from wastewater viral titers is orders of magnitude greater than the number of confirmed clinical cases and therefore may significantly impact efforts to understand the case fatality rate and progression of disease. These data may help inform decisions surrounding the advancement or scale-back of social distancing and quarantine efforts based on dynamic wastewater catchment-level estimations of prevalence.
21 July 2020, mSystems
-
Research Article
A recurrent mutation at position 26,340 of SARS-CoV-2 is associated with failure of the E-gene qRT-PCR utilized in a commercial dual-target diagnostic assay
Control of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires accurate laboratory testing to identify infected individuals, while also clearing essential staff to continue work. At the current time a number of qRT-PCR assays have been developed to identify SARS-CoV-2, targeting multiple positions in the viral genome. While the mutation rate of SARS-CoV-2 is moderate, given the large number of transmission chains it is prudent to monitor circulating viruses for variants that might compromise these assays. Here we report the identification of a C-to-U transition at position 26,340 of the SARS-CoV-2 genome which is associated with failure of the cobas® SARS-CoV-2 E-gene qRT-PCR in eight patients. As the cobas® SARS-CoV-2 assay targets two positions in the genome, the individuals carrying this variant were still called as SARS-CoV-2 positive. Whole genome sequencing of SARS-CoV-2 showed all to carry closely related viruses. Examination of viral genomes deposited on GISAID showed this mutation has arisen independently at least four times. This work highlights the necessity of monitoring SARS-CoV-2 for the emergence of SNPs which might adversely affect RT-PCRs used in diagnostics. Additionally, it argues that two regions in SARS-CoV-2 should be targeted to avoid false negatives.
Accepted Manuscript Posted 20 July 2020, JCM; Final Article Posted 22 September 2020
-
Research Article
Modelling the inactivation of viruses from the Coronaviridae family in response to temperature and relative humidity in suspensions or surfaces
The prediction of the persistence of SARS-CoV-2 on fomites is essential to investigate the importance of contact transmission. This study collects available information on inactivation kinetics of coronaviruses in both solid and liquid fomites and creates a mathematical model for the impact of temperature and relative humidity on virus persistence. The predictions of the model can support more robust decision-making and could be useful in various public health contexts. Having a calculator for the natural clearance of SARS-CoV-2 depending on temperature and relative humidity could be a valuable operational tool for public authorities.
Accepted Manuscript Posted 17 July 2020, AEM; Final Article Posted 1 September 2020
-
Research Article
Discovery of M Protease inhibitors encoded by SARS-CoV-2
The COVID-19 pandemic caused by SARS-CoV-2 is a health threat worldwide. Viral main protease (Mpro, also called 3C-like protease, 3CLpro) is a therapeutic target for drug discovery. Herein, we report that GC376, a broad-spectrum inhibitor targeting Mpro in the picornavirus-like supercluster, is potent inhibitor for the Mpro encoded by SARS-CoV-2 with half-maximum inhibitory concentration (IC50) of 26.4±1.1 nM. In this study, we also show that GC376 inhibits SARS-CoV-2 replication with a half-maximum effective concentration (EC50) of 0.91±0.03 μM. Only a small portion of SARS-CoV-2-Mpro was covalently modified in the excess of GC376 as evaluated by mass spectrometry analysis; indicating that improved inhibitors are needed. Subsequently, molecular docking analysis revealing the recognition and binding groups of GC376 within the active site of SARS-CoV-2 Mpro provides important new information for the optimization of GC376. Given that sufficient safety and efficacy data are available for GC376 as an investigational veterinary drug, expedited development of GC376, or its optimized analogues, for treatment of SARS-CoV-2 infection in human is recommended.
Accepted Manuscript Posted 15 July 2020, AAC; Final Article Posted 20 August 2020