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Review 2: "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 2: "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:

  • Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.

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Review:

In this meticulously conducted study, the authors evaluated the kinetics of SARS-CoV-2 infection markers over the course of infection in a cohort of 95 individuals with mild COVID who were followed up at multiple time points. Participants were probable first-time infected adults and were unvaccinated at the time of infection. Infecting strains were either the original virus or early VOCs, including epsilon, alpha or gamma. Infection markers that were measured included RT-PCR (CT and viral load); culture positivity and virus titre as determined by TCID50 in veroE6AT cells, S and N antigen positivity on nasal samples. Using these markers, they plotted trajectories over the course of infection.

Their results largely supplement data on infectious marker kinetics already out there, but the studies were meticulously done and provide quantitative data on viral load and titre of culturable virus in the respiratory tract of participants over the course of infection. Notable findings were that N antigen positivity in nasal samples correlated strongly with infectivity (using culture positivity as a proxy) and provided a better indicator of when it was safe to end isolation than clinical symptom severity or PCR status.

It is an excellent study and provides detailed baseline data on disease markers in patients with primary infection with early SARS-CoV-2 strains. The evidence provided by this study is strong. At this stage of the pandemic, however, the current focus has shifted to determining infection marker trajectories in vaccinated individuals, re-infections and infections with later variants, in particular Omicron. The extent to which these factors affect disease markers requires study. A repeat of this study in contemporary cases would be very interesting and would provide comparable data to answer questions on how previous immunity from vaccination or natural infection impacts on infectious marker reliability in re-infected individuals, in particular in the era of Omicron. This is not a criticism of the current study, but rather reflects the ever changing diagnostic challenges.


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