Dataset Information

SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.

ABSTRACT:

Background

Viral load kinetics and duration of viral shedding are important determinants for disease transmission. We aimed to characterise viral load dynamics, duration of viral RNA shedding, and viable virus shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids, and to compare SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) viral dynamics.

Methods

In this systematic review and meta-analysis, we searched databases, including MEDLINE, Embase, Europe PubMed Central, medRxiv, and bioRxiv, and the grey literature, for research articles published between Jan 1, 2003, and June 6, 2020. We included case series (with five or more participants), cohort studies, and randomised controlled trials that reported SARS-CoV-2, SARS-CoV, or MERS-CoV infection, and reported viral load kinetics, duration of viral shedding, or viable virus. Two authors independently extracted data from published studies, or contacted authors to request data, and assessed study quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist tools. We calculated the mean duration of viral shedding and 95% CIs for every study included and applied the random-effects model to estimate a pooled effect size. We used a weighted meta-regression with an unrestricted maximum likelihood model to assess the effect of potential moderators on the pooled effect size. This study is registered with PROSPERO, CRD42020181914.

Findings

79 studies (5340 individuals) on SARS-CoV-2, eight studies (1858 individuals) on SARS-CoV, and 11 studies (799 individuals) on MERS-CoV were included. Mean duration of SARS-CoV-2 RNA shedding was 17·0 days (95% CI 15·5-18·6; 43 studies, 3229 individuals) in upper respiratory tract, 14·6 days (9·3-20·0; seven studies, 260 individuals) in lower respiratory tract, 17·2 days (14·4-20·1; 13 studies, 586 individuals) in stool, and 16·6 days (3·6-29·7; two studies, 108 individuals) in serum samples. Maximum shedding duration was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stools, and 60 days in serum. Pooled mean SARS-CoV-2 shedding duration was positively associated with age (slope 0·304 [95% CI 0·115-0·493]; p=0·0016). No study detected live virus beyond day 9 of illness, despite persistently high viral loads, which were inferred from cycle threshold values. SARS-CoV-2 viral load in the upper respiratory tract appeared to peak in the first week of illness, whereas that of SARS-CoV peaked at days 10-14 and that of MERS-CoV peaked at days 7-10.

Interpretation

Although SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2.

Funding

None.

SUBMITTER: Cevik M

PROVIDER: S-EPMC7837230 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.

Cevik Muge M Tate Matthew M Lloyd Ollie O Maraolo Alberto Enrico AE Schafers Jenna J Ho Antonia A

The Lancet. Microbe 20201119 1

<h4>Background</h4>Viral load kinetics and duration of viral shedding are important determinants for disease transmission. We aimed to characterise viral load dynamics, duration of viral RNA shedding, and viable virus shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids, and to compare SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) viral dynamics.<h4>Methods</h4>In this systematic review and meta-analysis, we searched ...[more]

PMID: 33521734

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Project description:IntroductionMildly symptomatic cases of Covid-19 in previously-well individuals form the majority of infections and also serve as potent vectors of transmission. The factors affecting the duration of SARS-CoV-2 RNA viral shedding (DVS) in these patients remain largely unknown.ObjectivesTo perform a systematic analysis of the clinical, radiologic, laboratory investigations in patients with few comorbidities infected with mild Covid-19 to identify factors associated with the DVS.MethodsIn this retrospective cohort study, patients with mild or asymptomatic Covid-19 were included. Baseline characteristics including age, nationality, comorbidities, concomitant medications, and type of isolation arrangement in the facility (single or in pairs) were collected. Clinical features and radiologic/haematologic findings were also collected. Taking day 28 as the cut-off, 187 patients who had a negative swab result up to day 28 (no prolonged DVS) were compared to 126 patients with a persistently positive result on or after day 28 (prolonged DVS).ResultsOf 964 consecutive patients included, 851 (88.3%) patients were symptomatic. 266 patients had a documented negative RT-PCR assay with a median DVS of 25 days (range: 13 to 96 days; interquartile range (IQR): 22 to 33 days). Patients isolated in pairs were associated with prolonged DVS (OR: 2.7; 95% CI: 1.7 to 4.5; p<0.0001) compared to those isolated individually. Among vital signs, only tachycardia was associated with prolonged DVS (OR: 2.6; 95% CI: 1.0 to 7.1; p = 0.03). Amongst investigations, only a raised CRP was associated with prolonged DVS (OR: 2.7; 95% CI: 1.1 to 6.8; p = 0.02).ConclusionsIn young, mildly symptomatic Covid-19 patients, prolonged DVS was associated with being isolated in pairs compared to individually. In situations where a negative RT-PCR test result is required, retesting in patients who were not isolated individually, or who had baseline tachycardia or a raised CRP, may be delayed to increase the yield of a negative result.

Project description:IntroductionThere is an evidence gap regarding the duration of SARS-CoV-2 shedding and of its variability across different care settings and by age, sex, income, and co-morbidities. Such evidence is part of understanding of infectivity and reinfection. We examine direct measures of viral shedding using a linked population-based health administrative dataset.MethodsLaboratory and sociodemographic databases for Ontario, Canada were linked to identify those testing positive (RT-PCR) between Jan. 15 and April 30, 2020 who underwent subsequent testing by May 31, 2020. To maximise use of available data, we computed two shedding duration estimates defined as the time between initial positive and most recent positive (documented shedding) or second of two negative tests (documented resolution). We also report multivariable results using quantile regression to examine subgroup differences.ResultsIn Ontario, of the 16,595 who tested positive before April 30, 2020, 6604 had sufficient subsequent testing to allow shedding duration calculation. Documented shedding median duration calculated in 4,889 (29% of 16,595) patients was 19 days (IQR 12-28). Documented resolution median duration calculated in 3,219 (19% of the 16,595) patients was 25 days (IQR 18-34). Long-term care residents had 3-5 day longer shedding durations using both definitions. Shorter documented shedding durations of 2-4 days were observed in those living in higher income neighbourhoods. Shorter documented resolution durations of 2-3 days were observed at the 25th% of the distribution in those aged 20-49. Only 11.5% of those with definitive negative test results reverted to negative status by day 14.ConclusionsViral shedding continued well beyond 14 days among this large subset of a population-based group with COVID-19, and longer still for long-term care residents and those living in less affluent neighborhoods. Our findings do not speak to duration of infectivity but are useful for understanding the expected duration of RT-PCR positivity and for identifying reinfection.

Dataset Information

SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.

Background

Methods

Findings

Interpretation

Funding

Publications

SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.

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