COVID 19 Special Collection
COVID-19 (SARS-CoV-2) Special Collection
Latest COVID-19 Articles
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Research Article
Analysis of Measles-Mumps-Rubella (MMR) Titers of Recovered COVID-19 Patients
COVID-19 has presented various paradoxes that, if understood better, may provide clues to controlling the pandemic, even before a COVID-19 vaccine is widely available. First, young children are largely spared from severe disease. Second, numerous countries have COVID-19 death rates that are as low as 1% of the death rates of other countries. Third, many people, despite prolonged close contact with someone who is COVID-19 positive, never test positive themselves. Fourth, nearly half of people who test positive for COVID-19 are asymptomatic. Some researchers have theorized that the measles-mumps-rubella (MMR) vaccine may be responsible for these disparities. The significance of our study is that it showed that mumps titers related to the MMR II vaccine are significantly and inversely correlated with the severity of COVID-19-related symptoms, supporting the theorized association between the MMR vaccine and COVID-19 severity.
20 November 2020, mBio
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Editorial
After COVID-19 We Will Need a New Research System. We Need To Start Planning Now
The world after COVID-19 will be significantly different than the one we thought we knew so well only months ago....
20 November 2020, mBio
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Research Article
Evaluation of Serological SARS-CoV-2 Lateral Flow Assays for Rapid Point of Care Testing
Rapid point-of-care tests (POCTs) for SARS-CoV-2-specific antibodies vary in performance. A critical need exists to perform head-to-head comparison of these assays. Performance of fifteen different lateral flow POCTs for the detection of SARS-CoV-2-specific antibodies was performed on a well characterized set of 100 samples. Of these, 40 samples from known SARS-CoV-2-infected, convalescent individuals (average of 45 days post symptom onset) were used to assess sensitivity. Sixty samples from the pre-pandemic era (negative control), that were known to have been infected with other respiratory viruses (rhinoviruses A, B, C and/or coronavirus 229E, HKU1, NL63 OC43) were used to assess specificity. The timing of seroconversion was assessed on five LFAs on a panel of 272 longitudinal samples from 47 patients of known time since symptom onset. For the assays that were evaluated, the sensitivity and specificity for any reactive band ranged from 55%-97% and 78%-100%, respectively. When assessing the performance of the IgM and the IgG bands alone, sensitivity and specificity ranged from 0%-88% and 80%-100% for IgM and 25%-95% and 90%-100% for IgG. Longitudinal testing revealed that median time post symptom onset to a positive result was 7 days (IQR 5.4, 9.8) for IgM and 8.2 days (IQR 6.3 to 11.3) for IgG. The testing performance varied widely among LFAs with most variation related to the sensitivity of the assays. The IgM band was most likely to misclassify pre-pandemic samples. The appearance of IgM and IgG bands occurred almost simultaneously.
Accepted Manuscript Posted 18 November 2020, JCM
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Observation
Handwashing and Detergent Treatment Greatly Reduce SARS-CoV-2 Viral Load on Halloween Candy Handled by COVID-19 Patients
The COVID-19 pandemic is leading to important tradeoffs between risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and mental health due to deprivation from normal activities, with these impacts being especially profound in children. Due to the ongoing pandemic, Halloween activities will be curtailed as a result of the concern that candy from strangers might act as fomites. Here, we demonstrate that these risks can be mitigated by ensuring that, prior to handling candy, the candy giver washes their hands and, after receipt, by washing candy with household dishwashing detergent. Even in the most extreme case, with candy deliberately coughed on by known COVID-19 patients, viral load was reduced dramatically after washing with household detergent. We conclude that with reasonable precautions, even if followed only by either the candy giver or the candy recipient, the risk of viral transmission by this route is very low.
17 November 2020, mSystems
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Letter to the Editor
Extraction-free methods for the detection of SARS-CoV-2 by RT-PCR: a comparison with the Cepheid Xpert Xpress SARS-CoV-2 assay across two medical centers
RT-PCR is the gold-standard for the diagnosis of SARS-CoV-2 infection, however, testing has been complicated by supply shortages and long turn-around times.…
Accepted Manuscript Posted 12 November 2020, JCM
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Minireview
Defensive Properties of Mucin Glycoproteins during Respiratory Infections—Relevance for SARS-CoV-2
Mucus plays a pivotal role in protecting the respiratory tract against microbial infections. It acts as a primary contact site to entrap microbes and facilitates their removal from the respiratory tract via the coordinated beating of motile cilia. The major components of airway mucus are heavily O-glycosylated mucin glycoproteins, divided into gel-forming mucins and transmembrane mucins. The gel-forming mucins MUC5AC and MUC5B are the primary structural components of airway mucus, and they enable efficient clearance of pathogens by mucociliary clearance. MUC5B is constitutively expressed in the healthy airway, whereas MUC5AC is upregulated in response to inflammatory challenge. MUC1, MUC4, and MUC16 are the three major transmembrane mucins of the respiratory tracts which prevent microbial invasion, can act as releasable decoy receptors, and activate intracellular signal transduction pathways. Pathogens have evolved virulence factors such as adhesins that facilitate interaction with specific mucins and mucin glycans, for example, terminal sialic acids. Mucin expression and glycosylation are dependent on the inflammatory state of the respiratory tract and are directly regulated by proinflammatory cytokines and microbial ligands. Gender and age also impact mucin glycosylation and expression through the female sex hormone estradiol and age-related downregulation of mucin production. Here, we discuss what is currently known about the role of respiratory mucins and their glycans during bacterial and viral infections of the airways and their relevance for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding the impact of microbe-mucin interaction in the respiratory tract could inspire the development of novel therapies to boost mucosal defense and combat respiratory infections.
12 November 2020, mBio
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Editorial
Too slow, less dough for SARS-CoV-2 tests? A Micro-Comic Strip
Laboratory testing for SARS-CoV-2 has been delayed in some laboratories due to high demand for testing and supply shortages. This has led to proposals and plans that reimbursement for delayed results be reduced or not paid at all (1, 2). Read the comic strip to find out more.
Accepted Manuscript Posted 11 November 2020, JCM
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Research Article
A Genome Epidemiological Study of SARS-CoV-2 Introduction into Japan
This study aimed to evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences from COVID-19 cases and to characterize their genealogical networks to demonstrate possible routes of spread in Japan. We found that there were at least two distinct SARS-CoV-2 introductions into Japan, initially from China and subsequently from other countries, including Europe. Our findings can help understand how SARS-CoV-2 entered Japan and contribute to increased knowledge of SARS-CoV-2 in Asia and its association with implemented stay-at-home/shelter-in-place/self-restraint/lockdown measures. This study suggested that it is necessary to formulate a more efficient containment strategy using real-time genome surveillance to support epidemiological field investigations in order to highlight potential infection linkages and mitigate the next wave of COVID-19 in Japan.
11 November 2020, mSphere
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Research Article
Daily Viral Kinetics and Innate and Adaptive Immune Response Assessment in COVID-19: a Case Series
This work is particularly important because it simultaneously assessed the virology, immunology, and clinical presentation of the same subjects, whereas other studies assess these separately. We describe the detailed viral and immune profiles of the first five patients infected by SARS-CoV-2 and quarantined in Geneva, Switzerland. Viral loads peaked at the very beginning of the disease, and infectious virus was shed only during the early acute phase of disease. No infectious virus could be isolated by culture 7 days after onset of symptoms, while viral RNA was still detectable for a prolonged period. Importantly, we saw that all patients, even those with mild symptoms, mount an innate response sufficient for viral control (characterized by early activated cytokines and monocyte responses) and develop specific immunity as well as cellular and humoral SARS-CoV-2-specific adaptive responses, which already begin to decline a few months after the resolution of symptoms.
11 November 2020, mSphere
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Research Article
Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives
The recent emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) in Wuhan, China in late 2019 and its subsequent spread to the rest of the world has created a pandemic situation unprecedented in modern history. While ACE2 has been identified as the viral receptor, cellular polysaccharides have also been implicated in virus entry. The SARS-CoV-2 spike glycoprotein (SGP) binds to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we report structure-based differences in anti-viral activity and affinity to SGP for several sulfated polysaccharides, including both well-characterized FDA-approved drugs and novel marine sulfated polysaccharides, which can be developed for prophylactic as well as therapeutic purposes.
Accepted Manuscript Posted 10 November 2020, JVI; Final Article Posted 13 January 2021
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Research Article
The Enzymatic Activity of the nsp14 Exoribonuclease Is Critical for Replication of MERS-CoV and SARS-CoV-2
The bifunctional nsp14 subunit of the coronavirus replicase contains 3′-to-5′ exoribonuclease (ExoN) and guanine-N7-methyltransferase domains. For the betacoronaviruses MHV and SARS-CoV, ExoN was reported to promote the fidelity of genome replication, presumably by mediating a form of proofreading. For these viruses, ExoN knockout mutants are viable while displaying an increased mutation frequency. Strikingly, we have now established that the equivalent ExoN knockout mutants of two other betacoronaviruses, MERS-CoV and SARS-CoV-2, are nonviable, suggesting an additional and critical ExoN function in their replication. This is remarkable in light of the very limited genetic distance between SARS-CoV and SARS-CoV-2, which is highlighted, for example, by 95% amino acid sequence identity in their nsp14 sequences. For (recombinant) MERS-CoV nsp14, both its enzymatic activities were evaluated using newly developed in vitro assays that can be used to characterize these key replicative enzymes in more detail and explore their potential as target for antiviral drug development.
9 November 2020, JVI
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Research Article
Type I Interferon Susceptibility Distinguishes SARS-CoV-2 from SARS-CoV
With the ongoing outbreak of COVID-19, differences between SARS-CoV-2 and the original SARS-CoV could be leveraged to inform disease progression and eventual treatment options. In addition, these findings could have key implications for animal model development as well as further research into how SARS-CoV-2 modulates the type I IFN response early during infection.
9 November 2020, JVI
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Research Article
Airborne disinfection by dry fogging efficiently inactivates SARS-CoV-2, mycobacteria and bacterial spores and shows the limits of commercial spore carriers for process control
Airborne disinfection is not only of crucial importance for the safe operation of laboratories and animal rooms where infectious agents are handled, but can also be used in public health emergencies like the current SARS-CoV-2 pandemic. We show that dry fogging a mixture of aPAA/HP is highly microbicidal, efficient, fast, robust, environmentally neutral, and a suitable airborne disinfection method. In addition, the low concentration of dispersed disinfectant, particularly for enveloped viral pathogens like SARS-CoV-2, entails high material compatibility. For these reasons and due to the relative simplicity of the procedure, it is an ideal disinfection method for hospital wards, ambulances, public conveyances and indoor community areas. Thus, we conclude that this method is an excellent choice for control of the current SARS-CoV-2 pandemic.
Accepted Manuscript Posted 6 November 2020, AEM
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Research Article
The SARS-CoV-2 conserved macrodomain is a mono-ADP-ribosylhydrolase
SARS-CoV-2 has recently emerged into the human population and has led to a worldwide pandemic of COVID-19 that has caused greater than 1.2 million deaths worldwide. With, no currently approved treatments, novel therapeutic strategies are desperately needed. All coronaviruses encode for a highly conserved macrodomain (Mac1) that binds to and removes ADP-ribose adducts from proteins in a dynamic post-translational process increasingly recognized as an important factor that regulates viral infection. The macrodomain is essential for CoV pathogenesis and may be a novel therapeutic target. Thus, understanding its biochemistry and enzyme activity are critical first steps for these efforts. Here we report the crystal structure of SARS-CoV-2 Mac1 in complex with ADP-ribose, and describe its ADP-ribose binding and hydrolysis activities in direct comparison to SARS-CoV and MERS-CoV Mac1 proteins. These results are an important first step for the design and testing of potential therapies targeting this unique protein domain.
Accepted Manuscript Posted 6 November 2020, JVI; Final Article Posted 13 January 2021
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Research Article
Long-Term Modeling of SARS-CoV-2 Infection of In Vitro Cultured Polarized Human Airway Epithelium
The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to >35 million confirmed cases and >1 million fatalities worldwide. SARS-CoV-2 mainly replicates in human airway epithelia in COVID-19 patients. In this study, we used in vitro cultures of polarized human bronchial airway epithelium to model SARS-CoV-2 replication for a period of 21 to 51 days. We discovered that in vitro airway epithelial cultures endure a long-lasting SARS-CoV-2 propagation with recurrent peaks of progeny virus release at an interval of approximately 7 to 10 days. Our study also revealed that SARS-CoV-2 infection causes airway epithelia damage with disruption of tight junction function and loss of cilia. Importantly, SARS-CoV-2 exhibits a polarity of infection in airway epithelium only from the apical membrane; it infects ciliated and goblet cells but not basal and club cells. Furthermore, the productive infection of SARS-CoV-2 requires a high viral load of over 2.5 × 105 virions per cm2 of epithelium. Our study highlights that the proliferation of airway basal cells and regeneration of airway epithelium may contribute to the recurrent infections.
6 November 2020, mBio