COVID 19 Special Collection
COVID-19 (SARS-CoV-2) Special Collection
Latest COVID-19 Articles
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Research Article
Suramin inhibits SARS-CoV-2 infection in cell culture by interfering with early steps of the replication cycle
The SARS-CoV-2 pandemic that originated from Wuhan, China, in December 2019 has impacted public health, society and economy and the daily lives of billions of people in an unprecedented manner. There are currently no specific registered antiviral drugs to treat or prevent SARS-CoV-2 infections. Therefore, drug repurposing would be the fastest route to provide at least a temporary solution while better, more specific drugs are being developed. Here we demonstrate that the antiparasitic drug suramin inhibits SARS-CoV-2 replication, protecting Vero E6 cells with an EC50 of ~20 μM, which is well below the maximum attainable level in human serum. Suramin also decreased the viral load by 2-3 logs when Vero E6 cells or cells of a human lung epithelial cell line (Calu-3) were treated. Time of addition and plaque reduction assays performed on Vero E6 cells showed that suramin acts on early steps of the replication cycle, possibly preventing binding or entry of the virus. In a primary human airway epithelial cell culture model, suramin also inhibited the progression of infection. The results of our preclinical study warrant further investigation and suggest it is worth evaluating whether suramin provides any benefit for COVID-19 patients, which obviously requires safety studies and well-designed, properly controlled randomized clinical trials.
Accepted Manuscript Posted 8 June 2020, AAC; Final Article Posted 22 July 2020
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Letter to the Editor
The good, the bad & the hoax: when publication instantaneously impacts treatment strategies for COVID-19
The COVID-19 pandemic is an unprecedented situation with physicians awaiting information on therapeutic advances to an extent hardly ever seen in medical history.…
Accepted Manuscript Posted 8 June 2020, AAC; Final Article Posted 22 July 2020
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Research Article
Clinical Performance of SARS-CoV-2 Molecular Testing
Molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the gold standard for diagnosis of coronavirus disease 2019 (COVID-19), but the clinical performance of these tests is still poorly understood, particularly with regard to disease course, patient-specific factors, and viral shedding. From 3/10/2020-5/1/2020 NewYork-Presbyterian laboratories performed 27,377 SARS-CoV-2 molecular assays from 22,338 patients. Repeat testing was performed for 3,432 patients, of which 2,413 had initial negative and 802 had initial positive results. Repeat-tested patients were more likely to have severe disease and low viral loads. The negative predictive value of the first day result among repeat-tested patients was 81.3% The clinical sensitivity of SARS-CoV-2 molecular assays was estimated between 58 % and 96%, depending on the unknown number of false negative results in single-tested patients. Conversion to negative was unlikely to occur before 15 to 20 days after initial testing or 20-30 days after the onset of symptoms, with 50% conversion occurring at 28 days after initial testing. Conversion from first day negative to positive results increased linearly with each day of testing, reaching 25% probability in 20 days. Sixty patients fluctuated between positive and negative results over several weeks suggesting caution when acting on single results. In summary, our study provides estimates of the clinical performance of SARS-CoV-2 molecular assays and suggests time frames for appropriate repeat testing, namely 15 to 20 days after a positive test and the same or next 2 days after a negative test in patients with high suspicion for COVID-19.
Accepted Manuscript Posted 8 June 2020, JCM; Final Article Posted 23 July 2020
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Commentary
A Public Health Laboratory Response to the COVID-19 Pandemic
An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in Wuhan, Hubei, China, in December 2019, and spread rapidly worldwide. The response by the Alberta Precision Laboratories, Public Health Laboratory (ProvLab), Alberta, Canada, included the development and implementation of nucleic acid detection based assays and dynamic changes in testing protocols for the identification of cases as the epidemic curve increased exponentially. This rapid response was essential to slow down and contain transmission and provide valuable time to the local health authorities to prepare appropriate response strategies. As of May 24, 2020, 236,077 specimens were tested with 6475 (2.74%) positives detected in the province of Alberta, Canada. Several commercial assays are now available; however, the response from commercial vendors to develop and market validated tests is a time-consuming process. In addition, the massive global demand made it difficult to secure a reliable commercial supply of testing kits and reagents. A public health laboratory serves a unique and important role in the delivery of health care. One of its functions is to anticipate and prepare for novel emerging pathogens with a plan for pandemic preparedness. Here we outline the response that involved the development and deployment of testing methodologies that evolved as SARS-CoV-2 spread world-wide, the challenges encountered, and mitigation strategies. We also provide insight into the organizational structure of how a public health response is coordinated in Alberta and its benefits.
Accepted Manuscript Posted 8 June 2020, JCM; Final Article Posted 23 July 2020
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Research Article
Performance Characteristics of Four High-Throughput Immunoassays for Detection of IgG Antibodies against SARS-CoV-2
The role of serologic testing for SARS-CoV-2, both in the clinical and public health settings, will continue to evolve as we gain increasing insight into our immune response to the virus. Here, we evaluated four high throughput serologic tests for detection of anti-SARS-CoV-2 IgG antibodies, including assays from Abbott Laboratories (Abbott Park, IL), Epitope Diagnostics Inc. (San Diego, CA), Euroimmun (Lubeck, Germany), and Ortho-Clinical Diagnostics (Rochester, NY), using a panel of serially collected serum samples (N=224) from 56 patients with confirmed COVID-19, healthy donor sera from 2018 and a cross-reactivity serum panel collected in early 2020. Sensitivity of the Abbott, Epitope, Euroimmun and Ortho-Clinical IgG assays in convalescent serum samples collected more than 14 days post symptom onset or initial positive RT-PCR result was 92.9% (78/84), 88.1% (74/84), 97.6% (82/84) and 98.8% (83/84), respectively. Among unique convalescent patients, sensitivity of the Abbott, Epitope, Euroimmun and Ortho-Clinical anti-SARS-CoV-2 IgG assays was 97.3% (36/37), 73% (27/37), 94.6% (35/37) and 97.3% (36/37), respectively. Overall assay specificity and positive predictive values based on a 5% prevalence rate are 99.6%/92.8%, 99.6%/90.6%, 98.0%/71.2% and 99.6%/92.5%, respectively, for the Abbott, Epitope, Euroimmun and Ortho-Clinical IgG assays. In conclusion, we show high sensitivity in convalescent sera and high specificity for the Abbott, Euroimmun and Ortho-Clinical anti-SARS-CoV-2 IgG assays. With the unprecedented influx of commercially available serologic tests for detection of antibodies against SARS-CoV-2, it remains imperative that laboratories thoroughly evaluate such assays for accuracy prior to implementation.
Accepted Manuscript Posted 8 June 2020, JCM; Final Article Posted 23 July 2020
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Letter to the Editor
Multi-Center Evaluation of the Cepheid Xpert Xpress SARS-CoV-2 Assay for the Detection of SARS-CoV-2 in Oropharyngeal Swab Specimens
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a global health concern that has spread worldwide since December 2019 (1-4).…
Accepted Manuscript Posted 5 June 2020, JCM; Final Article Posted 23 July 2020
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Genome Sequences
Complete Genome Sequence of a SARS-CoV-2 Strain Isolated in Northern Germany
Here, we describe the complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain isolated from an oropharyngeal swab sample from a female patient with COVID-19 who was infected in Hamburg, northern Germany.
4 June 2020, MRA
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Letter to the Editor
Pre-Procedural Surveillance Testing for SARS-CoV-2 in an Asymptomatic Population in the Seattle Region Shows Low Rates of Positivity
Seattle region hospitals have been impacted for several months by community spread of the coronavirus disease of 2019 (COVID-19).…
Accepted Manuscript Posted 3 June 2020, JCM; Final Article Posted 23 July 2020
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Research Article
Clinical performance of the Luminex NxTAG CoV Extended Panel for SARS-CoV-2 detection in nasopharyngeal specimens of COVID-19 patients in Hong Kong
In December 2019, the coronavirus disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was first reported in the Hubei Province of China and later spread all over the world. There was an urgent need of a high-throughput molecular testing for screening the COVID-19 patients in the community. The Luminex NxTAG CoV Extended Panel is a high-throughput FDA emergency use authorized molecular diagnostic assay for SARS-CoV-2 detection. This system targets three genes (ORF1ab, N and E gene) of SARS-CoV-2, ORF1ab region of SARS-CoV and ORF5 region of MERS-CoV. In this study, we evaluated the diagnostic performance of this system with nasopharyngeal swab specimens of 214 suspected COVID-19 patients in Hong Kong. The results were compared with our routine COVID-19 RT-PCR protocol with LightMix SarbecoV E-gene kit and an in-house RdRp/Hel RT-PCR assay. The NxTAG CoV Extended panel demonstrated a 97.8% sensitivity and 100% specificity to SARS-CoV-2 in nasopharyngeal specimens. On low viral load specimens, the sensitivity of the NxTAG panel could still maintain at 85.71%. High agreement was observed between the NxTAG panel and the routine COVID-19 RT-PCR protocol (kappa value = 0.98). Overall the E gene target of the NxTAG panel demonstrated the highest sensitivity among the three SARS-CoV-2 targets while the N gene targets demonstrated the least. In conclusion, the NxTAG CoV Extended Panel is simple to use and it has high diagnostic sensitivity and specificity to SARS-CoV-2 in nasopharyngeal specimens. we recommend this diagnostic system for high-throughput COVID-19 screening in the community.
Accepted Manuscript Posted 1 June 2020, JCM; Final Article Posted 23 July 2020
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Research Article
Performance of Abbott ID NOW COVID-19 rapid nucleic acid amplification test in nasopharyngeal swabs transported in viral media and dry nasal swabs, in a New York City academic institution
The recent emergence of the SARS-CoV-2 pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real time RT-PCR platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. Both platforms demonstrate comparable performance; however, the run times for each assay are 3.5 hours and 45 minutes, respectively. In search for a platform with shorter turnaround time, we sought to evaluate the recently released Abbott ID NOW COVID-19 assay which is capable of producing positive results in as little as 5 minutes. We present here the results of comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media and comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media for Cepheid and dry nasal swabs for Abbott ID NOW. Regardless of method of collection and sample type, Abbott ID NOW COVID-19 had negative results in a third of the samples that tested positive by Cepheid Xpert Xpress when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs.
Accepted Manuscript Posted 29 May 2020, JCM; Final Article Posted 23 July 2020
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Research Article
Novel Immunoglobulin Domain Proteins Provide Insights into Evolution and Pathogenesis of SARS-CoV-2-Related Viruses
The ongoing COVID-19 pandemic strongly emphasizes the need for a more complete understanding of the biology and pathogenesis of its causative agent SARS-CoV-2. Despite intense scrutiny, several proteins encoded by the genomes of SARS-CoV-2 and other SARS-like coronaviruses remain enigmatic. Moreover, the high infectivity and severity of SARS-CoV-2 in certain individuals make wet-lab studies currently challenging. In this study, we used a series of computational strategies to identify several fast-evolving regions of SARS-CoV-2 proteins which are potentially under host immune pressure. Most notably, the hitherto-uncharacterized protein encoded by ORF8 is one of them. Using sensitive sequence and structural analysis methods, we show that ORF8 and several other proteins from alpha- and beta-coronavirus comprise novel families of immunoglobulin domain proteins, which might function as potential immune modulators to delay or attenuate the host immune response against the viruses.
29 May 2020, mBio
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Perspective
Pandemic COVID-19 Joins History’s Pandemic Legion
With great apprehension, the world is now watching the birth of a novel pandemic already causing tremendous suffering, death, and disruption of normal life. Uncertainty and dread are exacerbated by the belief that what we are experiencing is new and mysterious. However, deadly pandemics and disease emergences are not new phenomena: they have been challenging human existence throughout recorded history. Some have killed sizeable percentages of humanity, but humans have always searched for, and often found, ways of mitigating their deadly effects. We here review the ancient and modern histories of such diseases, discuss factors associated with their emergences, and attempt to identify lessons that will help us meet the current challenge.
29 May 2020, mBio
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Author Reply
Reply to Siniorakis et al., “COVID-19 Interference with Renin-Angiotensin System in the Context of Heart Failure”
We thank Eftychios Siniorakis and colleagues for their thoughtful letter on how repurposing statins and angiotensin receptor blockers (ARBs) for coronavirus disease 2019 (COVID-19) treatment might affect patients with heart failure....
29 May 2020, mBio
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Research Article
Influence of Different Inactivation Methods on Severe Acute Respiratory Syndrome Coronavirus 2 RNA Copy Number
The outbreak of COVID-19 has spread across the world and was characterized as a pandemic. To protect medical laboratory personnel from infection, most laboratories inactivate the clinical samples before testing. However, the effect of inactivation on the detection results remains unknown. Here, we used a digital PCR assay to determine the absolute SARS-CoV-2 RNA copy number in 63 nasopharyngeal samples and assess the effect of inactivation methods on viral RNA copy number. Viral inactivation was performed with three different methods: (1) incubation with TRIzol® LS Reagent for 10 min at room temperature, (2) heating in a waterbath at 56°C for 30 min, and (3) high-temperature treatment, including 121°C autoclaving for 20 min, 100°C boiling for 20 min, and 80°C heating for 20 min. Compared to the amount of RNA in the original sample, TRIzol treatment destroyed 47.54% of N gene and 39.85% of ORF 1ab. For samples treated at 56°C for 30 min, the copy number of N gene and ORF 1ab was reduced by 48.55% and 56.40%, respectively. Viral RNA copy number dropped by 50–66% after 80°C heating for 20 min. Nearly no viral RNA was detected after autoclaving at 121°C or boiling at 100°C for 20 min. These results indicated that inactivation reduced the quantity of detectable viral RNA and may cause false negative results especially in weakly positive cases. Thus, TRIzol is recommended for sample inactivation in comparison to heat inactivation as Trizol has the least effect on RNA copy number among the tested methods.
Accepted Manuscript Posted 28 May 2020, JCM; Final Article Posted 23 July 2020
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Genome Sequences
Complete Genome Sequence of SARS-CoV-2 in a Tiger from a U.S. Zoological Collection
This report describes the identification and characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a Malayan tiger in a U.S. zoo.
28 May 2020, MRA