COVID 19 Special Collection
COVID-19 (SARS-CoV-2) Special Collection
Latest COVID-19 Articles
-
Commentary
Coordinating and Assisting Research at the SARS-CoV-2/Microbiome Nexus
Although the COVID-19 pandemic is caused by a single virus, the rest of the human microbiome appears to be involved in the disease and could influence vaccine responses while offering opportunities for microbiome-directed therapeutics. The newly formed Microbiome Centers Consortium (MCC) surveyed its membership and identified four ways to leverage the strengths and experience of microbiome centers in the response to the COVID-19 pandemic. To meet these needs, the MCC will provide a platform to coordinate clinical and environmental research, assist with practical obstacles, and help communicate the connections between the microbiome and COVID-19. We ask that microbiome researchers join us in these efforts to address the ongoing pandemic.
1 December 2020, mSystems
-
Research Article
A Versatile Reporter System to Monitor Virus Infected Cells and Its Application to Dengue Virus and SARS-CoV-2
Reporter systems are useful tools for fast and quantitative visualization of virus infected cells within a host cell population. Here we describe a reporter system that takes advantage of virus-encoded proteases that are expressed in infected cells to cleave an ER-anchored fluorescent protein fused to a nuclear localization sequence. Upon cleavage, the GFP moiety translocates to the nucleus, allowing for rapid detection of the infected cells. Using this system, we demonstrate reliable reporting activity for two major human pathogens from the Flaviviridae and the Coronaviridae families: dengue virus and SARS-CoV-2. We apply this reporter system to live cell imaging and use it for proof-of-concept to validate antiviral activity of a nucleoside analogue. This reporter system is not only an invaluable tool for the characterization of viral replication, but also for the discovery and development of antivirals that are urgently needed to halt the spread of these viruses.
Accepted Manuscript Posted 30 November 2020, JVI
-
Research Article
Inference of Active Viral Replication in Cases with Sustained Positive RT-PCRs for SARS-CoV-2
The purpose of this study was to detect COVID-19 cases with persistent positive RT-PCR results for SARS-CoV-2, for which viable virus can be inferred, due to the presence of subgenomic (SG) viral RNA, which is expressed only in replicating viruses. RNA remnants, purified from diagnostic nasopharyngeal specimens, were used as templates for RT-PCR specific detection of SG E gene RNA. As controls, we also detected viral genomic RNA for the E gene and/or a human housekeeping gene (RNase P). We assessed the samples of 60 RT-PCR-positive cases with a prolonged viral SARS-CoV-2 shedding (24-101 days) since the first diagnostic RT-PCR. SG viral RNA was detected in 12/60 (20%) of the persistent cases, 28-79 days after the onset of symptoms. The age range of the cases with prolonged viral shedding and presence of SG RNA was quite wide (40-100 years), and they were equally distributed between males (42%) and females (58%). None was HIV positive, although seven were immunosuppressed. According to the severity of the COVID-19 episodes they were mild (40%), intermediate (20%), and severe (40%). In a percentage of persistent positive SARS-CoV-2 PCR positive cases the presence of actively replicating virus may be inferred, far beyond diagnosis. We should not assume a universal lack of infectiousness for COVID-19 cases with prolonged viral shedding.
Accepted Manuscript Posted 25 November 2020, JCM
-
Research Article
Evaluating Ten Commercially-Available SARS-CoV-2 Rapid Serological Tests Using the STARD (Standards for Reporting of Diagnostic Accuracy Studies) Method
Numerous SARS-CoV-2 rapid serological tests have been developed, but their accuracy has usually been assessed using very few samples, and rigorous comparisons between these tests are scarce. In this study, we evaluated and compared 10 commercially-available SARS-CoV-2 rapid serological tests using the STARD methodology (Standards for Reporting of Diagnostic Accuracy Studies). 250 sera from 159 PCR-confirmed SARS-CoV-2 patients (collected from 0 to 32 days after onset of symptoms) were tested with rapid serological tests. Control sera (N = 254) were retrieved from pre-COVID periods from patients with other coronavirus infections (N = 11), positive rheumatoid factors (N = 3), IgG/IgM hyperglobulinemia (N = 9), malaria (n = 5), or no documented viral infection (N = 226). All samples were tested using rapid lateral flow immunoassays (LFIA) from 10 manufacturers. Only four tests achieved ≥98% specificity, with other tests ranging from 75.7%-99.2%. Sensitivities varied by the day of sample collection, from 31.7%-55.4% (Days 0-9), 65.9%-92.9% (Days 10-14), and 81.0%-95.2% (>14 days) after the onset of symptoms, respectively. Only three tests evaluated met French Health Authorities’ thresholds for SARS-CoV-2 serological tests (≥90% sensitivity + ≥98% specificity). Overall, the performances between tests varied greatly, with only a third meeting acceptable specificity and sensitivity thresholds. Knowing the analytical performance of these tests will allow clinicians and most importantly laboratorians to use them with more confidence, could help determine the general population’s immunological status, and may help to diagnose some patients with false-negative RT-PCR results.
Accepted Manuscript Posted 25 November 2020, JCM
-
Research Article
Saliva is a Promising Alternative Specimen for the Detection of SARS-CoV-2 in Children and Adults
Testing efforts for SARS-CoV-2 have been burdened by the scarcity of testing materials and personal protective equipment for health care workers. The simple and painless process of saliva collection allows for widespread testing, but enthusiasm is hampered by variable performance compared to nasopharyngeal swab (NPS) samples. We prospectively collected paired NPS and saliva samples from a total of 300 unique adult and pediatric patients. SARS-CoV-2 RNA was detected in 32.2% (97/300) of the individuals using the TaqPath COVID-19 Combo Kit (Thermo Fisher). Performance of saliva and NPS were compared against the total number of positives regardless of specimen type. The overall concordance for saliva and NPS was 91.0% (273/300) and 94.7% (284/300), respectively. The positive percent agreement (PPA) for saliva and NPS was 81.4% (79/97) and 89.7% (87/97), respectively. Saliva detected 10 positive cases that were negative by NPS. In symptomatic and asymptomatic pediatric patients not previously diagnosed with COVID-19, the performances of saliva and NPS were comparable (PPA: 82.4% vs 85.3%). The overall PPA for adults were 83.3% and 90.7% for saliva and NPS, respectively, with saliva detecting 4 cases less than NPS. However, saliva performance in symptomatic adults was identical to NPS (PPA of 93.8%). With lower cost and self-collection capabilities, saliva can be an appropriate alternative sample choice to NPS for detection of SARS-CoV-2 in children and adults.
Accepted Manuscript Posted 25 November 2020, JCM
-
Research Article
Comparison of Quidel Sofia SARS FIA Test to Hologic Aptima SARS-CoV-2 TMA Test for Diagnosis of COVID-19 in Symptomatic Outpatients
The Quidel Sofia SARS FIA test (SOFIA) is a rapid antigen immunoassay for detection of SARS-CoV-2 viral proteins from nasal or nasopharyngeal swab specimens. The purpose of this study was to compare the results of the SOFIA test to the Hologic Aptima SARS-CoV-2 TMA test (APTIMA TMA), a high-throughput molecular diagnostic test that uses transcription mediated amplification for detection of SARS-CoV-2 nucleic acid from upper respiratory specimens. Three hundred and 40-seven symptomatic patients, from an urgent care center in an area with a high prevalence of SARS-CoV-2 infections, were tested in parallel using nasal swabs on the SOFIA test and nasopharyngeal swabs on the APTIMA TMA test. The SOFIA test demonstrated an 82.0% positive percent agreement (PPA) compared to the APTIMA TMA test for symptomatic patients tested ≤ 5 days from symptom onset and a 54.5% PPA for symptomatic patients > 5 days from symptom onset. The Cepheid Xpert Xpress SARS-CoV-2 RT-PCR test was used to determine the cycle threshold (Ct) value from any specimens that were discrepant between the SOFIA and APTIMA TMA tests. Using a Ct value of ≤ 35 as a surrogate for SARS-CoV-2 culture positivity, we estimate that the SOFIA test detected 87.2% of symptomatic patients tested ≤ 5 days from symptom onset that were likely to be culture positive.
Accepted Manuscript Posted 25 November 2020, JCM
-
Research Article
Clinical performance of the point-of-care cobas Liat for detection of SARS-CoV-2 in 20 minutes: A multicenter study
Highly accurate testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the point of care (POC) is an unmet diagnostic need in emergency care and time-sensitive outpatient care settings. Reverse transcription-polymerase chain reaction (RT-PCR) technology is the gold-standard for SARS-CoV-2 diagnostics. We performed a multi-site United States (US) study comparing the clinical performance of the first US Food and Drug Administration (FDA) authorized POC RT-PCR test for detection of SARS-CoV-2 in 20 minutes, the cobas® Liat SARS-CoV-2 & Influenza A/B nucleic acid test, to the most widely used RT-PCR laboratory test, the cobas® 68/8800 SARS-CoV-2 test. Clinical nasopharyngeal swab specimens from 444 patients with 357 evaluable specimens at five US clinical laboratories were enrolled from September 21, 2020 to October 23, 2020. The overall agreement between the Liat and 68/8800 systems for SARS-CoV-2 diagnostics was 98.6% (352/357). Using Liat, positive percent agreement for SARS-CoV-2 was 100% (162/162) and the negative percent agreement was 97.4% (190/195). The Liat is an RT-PCR POC test that provides highly accurate SARS-CoV-2 results in 20 minutes with equivalent performance to high-throughput laboratory molecular testing. Rapid RT-PCR testing at the POC can enable more timely infection control and individual care decisions for Coronavirus Disease 2019.
Accepted Manuscript Posted 25 November 2020, JCM
-
Research Article
Conserved Genomic Terminals of SARS-CoV-2 as Coevolving Functional Elements and Potential Therapeutic Targets
The coronavirus disease 2019 (COVID-19) outbreak is having a dramatic global effect on public health and the economy. As of October 2020, SARS-CoV-2 has been detected in over 189 countries, has infected over 40 million people, and is responsible for more than 1 million deaths. The genome of SARS-CoV-2 is small but complex, and its functions and interactions with human host factors are being studied extensively. The significance of our study is that, using extensive SARS-CoV-2 genome analysis techniques, we identified potential interacting human host microRNA targets that share similarity with those of influenza A virus H1N1. Our study results will allow the development of virus-host interaction models that will enhance our understanding of SARS-CoV-2 pathogenesis and motivate the exploitation of both the interacting viral and host factors as therapeutic targets.
25 November 2020, mSphere
-
Research Article
Detection of SARS-CoV-2 antibodies in oral fluid obtained using a rapid collection device
Current commercially available methods for reliably detecting antibodies against SARS-CoV-2 remain expensive and inaccessible due to the need for whole blood collection by highly trained phlebotomists using personal protective equipment (PPE). We have evaluated an antibody detection approach using the OraSure Technologies’ Oral Antibody Collection Device (OACD) and their proprietary SARS-CoV-2 total antibody detection enzyme-linked immunosorbent assay (ELISA). We found that the OraSure test for total antibody detection in oral fluid had comparable sensitivity and specificity to commercially available serum-based ELISAs for SARS-CoV-2 antibody detection while allowing for a more accessible specimen collection with the potential for self-collection.
Accepted Manuscript Posted 24 November 2020, JCM
-
Research Article
Structure of nonstructural protein 1 from SARS-CoV-2
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic. One protein known to play a critical role in the coronavirus life cycle is nonstructural protein1 (nsp1). As such, it has been highlighted in numerous studies as a target for both the development of antivirals and for the design of live-attenuated vaccines. Here we report the high-resolution crystal structure of nsp1 derived from SARS-CoV-2 at 1.77 Å resolution. This structure will facilitate future studies focusing on understanding the relationship between structure and function for nsp1. In turn, understanding these structure-function relationships will allow nsp1 to be fully exploited as a target for both antiviral development and vaccine design.
Accepted Manuscript Posted 24 November 2020, JVI
-
Research Article
Off-target In Vitro Profiling Demonstrates that Remdesivir Is a Highly Selective Antiviral Agent
Remdesivir (RDV, GS-5734), the first FDA-approved antiviral for the treatment of COVID-19, is a single diastereomer monophosphoramidate prodrug of an adenosine analogue. It is intracellularly metabolized into the active triphosphate form, which in turn acts as a potent and selective inhibitor of multiple viral RNA polymerases. RDV has broad-spectrum activity against members of the coronavirus family such as SARS-CoV-2, SARS-CoV, and MERS-CoV, as well as filoviruses and paramyxoviruses. To assess potential for off-target toxicity, RDV was evaluated in a set of cellular and biochemical assays. Cytotoxicity was evaluated in a set of relevant human cell lines and primary cells. In addition, RDV was evaluated for mitochondrial toxicity under aerobic and anaerobic metabolic conditions, and for the effects on mitochondrial DNA content, mitochondrial protein synthesis, cellular respiration, and induction of reactive oxygen species. Lastly, the active 5’-triphosphate metabolite of RDV, GS-443902, was evaluated for potential interaction with human DNA and RNA polymerases. Among all of the human cells tested under 5-14 days of continuous exposure, RDV’s CC50 values ranged from 1.7 to >20 μM, resulting in selectivity indices (SI, CC50/EC50) from >170 to 20,000, with respect to RDV anti-SARS-CoV-2 activity (EC50 of 9.9 nM in human airway epithelial cells). Overall, the cellular and biochemical assays demonstrated a low potential of RDV for off-target toxicity including mitochondria-specific toxicity, consistent with the reported clinical safety profile.
Accepted Manuscript Posted 23 November 2020, AAC; Final Article Posted 21 January 2021
-
Research Article
A Valid Warning or Clinical Lore: An Evaluation of Safety Outcomes of Remdesivir in Patients with Impaired Renal Function from a Multicenter Matched Cohort
Per prescribing guidance, remdesivir is not recommended for SARS-CoV-2 in patients with renal disease given the absence of safety data in this patient population. This study was a multi-center, retrospective chart review of hospitalized patients with SARS-CoV-2 who received remdesivir. Safety outcomes were compared between patients with an estimated creatinine clearance (eCrCl) < 30 mL/min and an eCrCl ≥ 30 mL/min. The primary endpoint was acute kidney injury (AKI) at the end of treatment (EOT). Of 359 patients who received remdesivir, 347 met inclusion criteria. Patients with an eCrCl < 30 mL/min were older [median, 80 years (IQR, 63.8-89) versus 62 (IQR, 54-74); P<0.001], were more likely to be on vasopressors on the day of remdesivir administration (30% versus 12.7%; P=0.003), and were more likely to be mechanically ventilated during remdesivir therapy (27.5% versus 12.4%; P=0.01) compared to those with an eCrCl ≥ 30 mL/min. Despite these confounders, there was no significant difference in the frequency of EOT AKI (5% versus 2.3%; P=0.283) or early discontinuation due to abnormal LFTs (0% versus 3.9%; P=0.374). Of the 5% of patients who developed EOT AKI on remdesivir with an eCrCl <30mL/min, no cases were attributable to remdesivir administration per the treating physician. Comparable safety outcomes were observed when 1:1 nearest neighbor matching was applied to account for baseline confounders. Remdesivir administration was not significantly associated with increased EOT AKI in patients with an eCrCl < 30mL/min compared to patients with an eCrCl ≥ 30mL/min.
Accepted Manuscript Posted 23 November 2020, AAC; Final Article Posted 21 January 2021
-
Research Article
Performance of the COVID-19 SEROSpeed IgM/IgG Rapid Test, an immunochromatographic assay for the diagnosis of SARS-CoV-2 infection: a multicenter European study
This study assessed the diagnostic performance of the new COVID-19 SEROSpeed IgM/IgG Rapid Test (BioSpeedia, spin-off of the Pasteur Institute of Paris) for the detection of antibodies against SARS-CoV-2 in comparison to other commercial antibody assays through a large cross-European study. The clinical specificity was assessed on 215 pre-pandemic sera (including some from patients with viral infections or autoimmune disorders). The clinical sensitivity was evaluated on 710 sera from 564 patients whose SARS-CoV-2 infection was confirmed by qRT-PCR and whose antibody response was compared to that measured by five other commercial tests. The kinetics of the antibody response were also analyzed in seven symptomatic patients. The specificity of the test (BioS) on pre-pandemic specimens was 98.1% (95% CI: 96.2-99.4). When tested on the 710 pandemic specimens, BioS showed an overall clinical sensitivity of 86.0% (95% CI: 0.83-0.89), with good concordance with the Euroimmun assay (overall concordance of 0.91; Cohen’s kappa coefficient of 0.62). Due in part to simultaneous detection of IgM and IgG for both S1 and N proteins, BioS exhibited the highest positive percent agreement ≥11 days post symptom onset (PSO). In conclusion, the BioS IgM/IgG rapid test was highly specific and demonstrated higher positive percent agreement compared to all the ELISA/CLIA commercial tests considered in this study. Moreover, by detecting the presence of antibodies prior to 11 days PSO in 78.2% of the patients, the BioS test increased the efficiency of the diagnosis of SARS-CoV-2 infection in the early stages of the disease.
Accepted Manuscript Posted 20 November 2020, JCM
-
Research Article
HTCC as a Polymeric Inhibitor of SARS-CoV-2 and MERS-CoV
The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus escaped the health care measures and rapidly spread in China and later globally, officially causing a pandemic and global crisis in March 2020. At present, different scenarios are being written to contain the virus, but the development of novel anticoronavirals for all highly pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity of previously developed by us HTCC compound, which may be used as a potential inhibitor of currently circulating highly pathogenic coronaviruses – SARS-CoV-2 and MERS-CoV.
Accepted Manuscript Posted 20 November 2020, JVI
-
Research Article
Metagenomic Next-Generation Sequencing of Nasopharyngeal Specimens Collected from Confirmed and Suspect COVID-19 Patients
SARS-CoV-2 has presented a rapidly accelerating global public health crisis. The ability to detect and analyze viral RNA from minimally invasive patient specimens is critical to the public health response. Metagenomic next-generation sequencing (mNGS) offers an opportunity to detect SARS-CoV-2 from nasopharyngeal (NP) swabs. This approach also provides information on the composition of the respiratory microbiome and its relationship to coinfections or the presence of other organisms that may impact SARS-CoV-2 disease progression and prognosis. Here, using direct Oxford Nanopore long-read third-generation metatranscriptomic and metagenomic sequencing of NP swab specimens from 50 patients under investigation for COVID-19, we detected SARS-CoV-2 sequences by applying the CosmosID bioinformatics platform. Further, we characterized coinfections and detected a decrease in the diversity of the microbiomes in these patients. Statistically significant shifts in the microbiome were identified among COVID-19-positive and -negative patients, in the latter of whom a higher abundance of Propionibacteriaceae and a reduction in the abundance of Corynebacterium accolens were observed. Our study also corroborates the growing evidence that increased SARS-CoV-2 RNA detection from NP swabs is associated with the early stages of disease rather than with severity of disease. This work illustrates the utility of mNGS for the detection and analysis of SARS-CoV-2 from NP swabs without viral target enrichment or amplification and for the analysis of the respiratory microbiome.
20 November 2020, mBio