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Review 1: "Duration of Viral Infectiousness and Correlation with Symptoms and Diagnostic Testing in Non-hospitalized Adults During Acute SARS-CoV-2 Infection: A Longitudinal Cohort Study"

This preprint assesses the duration of viral infectiousness and correlation with symptoms during an acute SARS-CoV-2 Infection. The reviewers find this study to be reliable to strong, stating that the study was well designed and confirms previous research findings.

Published onOct 28, 2022
Review 1: "Duration of Viral Infectiousness and Correlation with Symptoms and Diagnostic Testing in Non-hospitalized Adults During Acute SARS-CoV-2 Infection: A Longitudinal Cohort Study"
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key-enterThis Pub is a Review of
Duration of viral infectiousness and correlation with symptoms and diagnostic testing in non-hospitalized adults during acute SARS-CoV-2 infection: A longitudinal cohort study
Description

AbstractBackgroundGuidelines for SARS-CoV-2 have relied on limited data on duration of viral infectiousness and correlation with COVID-19 symptoms and diagnostic testing.MethodsWe enrolled ambulatory adults with acute SARS-CoV-2 infection and performed serial measurements of COVID-19 symptoms, nasal swab viral RNA, nucleocapsid (N) and spike (S) antigens, and replication-competent SARS-CoV-2 by culture. We determined average time from symptom onset to a first negative test result and estimated risk of infectiousness, as defined by a positive viral culture.ResultsAmong 95 adults, median [interquartile range] time from symptom onset to first negative test result was 9 [5] days, 13 [6] days, 11 [4] days, and >19 days for S antigen, N antigen, viral culture growth, and viral RNA by RT-PCR, respectively. Beyond two weeks, viral cultures and N antigen titers were rarely positive, while viral RNA remained detectable among half (26/51) of participants tested 21-30 days after symptom onset. Between 6-10 days from symptom onset, N antigen was strongly associated with viral culture positivity (relative risk=7.61, 95% CI: 3.01-19.2), whereas neither viral RNA nor symptoms were associated with culture positivity. During the 14 days following symptom onset, presence of N antigen (adjusted relative risk=7.66, 95% CI: 3.96-14.82), remained strongly associated with viral culture positivity, regardless of COVID-19 symptoms.ConclusionsMost adults have replication-competent SARS-CoV-2 for 10-14 after symptom onset, and N antigen testing is a strong predictor of viral infectiousness. Within two weeks from symptom onset, N antigen testing, rather than absence of symptoms or viral RNA, should be used to safely discontinue isolation.FundingBill and Melinda Gates Foundation

RR:C19 Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review:

The authors assessed the infectiousness of the respiratory specimens collected during the course of the disease from symptomatic COVID-19 patients. Viral culture was used as the standard of infectiousness. Another two diagnostic assays, antigen and RT-PCR assays were used to correlate with infectiousness. The manuscript was well written and easy to follow. The objectives were clear and correlated with the methods used. The conclusions were concordant with the results presented. The readers were alerted to the limitations of the study. The outcomes of the study could contribute to the knowledge of SARS-CoV-2 viral kinetics.

I only have two minor comments on the current version of the manuscript. In the alternative angle of views, the results shown in this study were concordant to previous studies. In terms of assay sensitivity, SARS-CoV-2 antigen assays correlated well with viral culture. Regarding the assumption of viral culture and infectiousness made by the authors, the authors shared similar views with the article written by Binnicker, 2021 (Binnicker MJ. Can Testing Predict SARS-CoV2 Infectivity? The Potential for Certain Methods To Be Surrogates for Replication-Competent Virus. J Clin Microbiol. 2021 Oct 19;59(11):e0046921.) due to the lack of a reliable predictor. The manuscript could be more comprehensive by discussing these two issues to further substantiate their results.



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