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Meta-Analysis
. 2021 Aug 24;118(34):e2109229118.
doi: 10.1073/pnas.2109229118.

Asymptomatic SARS-CoV-2 infection: A systematic review and meta-analysis

Pratha Sah  1 , Meagan C Fitzpatrick  1   2 , Charlotte F Zimmer  1 , Elaheh Abdollahi  3 , Lyndon Juden-Kelly  3 , Seyed M Moghadas  3 , Burton H Singer  4 , Alison P Galvani  1
Affiliations
Meta-Analysis

Asymptomatic SARS-CoV-2 infection: A systematic review and meta-analysis

Pratha Sah et al. Proc Natl Acad Sci U S A. .

Abstract

Quantification of asymptomatic infections is fundamental for effective public health responses to the COVID-19 pandemic. Discrepancies regarding the extent of asymptomaticity have arisen from inconsistent terminology as well as conflation of index and secondary cases which biases toward lower asymptomaticity. We searched PubMed, Embase, Web of Science, and World Health Organization Global Research Database on COVID-19 between January 1, 2020 and April 2, 2021 to identify studies that reported silent infections at the time of testing, whether presymptomatic or asymptomatic. Index cases were removed to minimize representational bias that would result in overestimation of symptomaticity. By analyzing over 350 studies, we estimate that the percentage of infections that never developed clinical symptoms, and thus were truly asymptomatic, was 35.1% (95% CI: 30.7 to 39.9%). At the time of testing, 42.8% (95% prediction interval: 5.2 to 91.1%) of cases exhibited no symptoms, a group comprising both asymptomatic and presymptomatic infections. Asymptomaticity was significantly lower among the elderly, at 19.7% (95% CI: 12.7 to 29.4%) compared with children at 46.7% (95% CI: 32.0 to 62.0%). We also found that cases with comorbidities had significantly lower asymptomaticity compared to cases with no underlying medical conditions. Without proactive policies to detect asymptomatic infections, such as rapid contact tracing, prolonged efforts for pandemic control may be needed even in the presence of vaccination.

Keywords: asymptomatic fraction; comorbidity; novel coronavirus; presymptomatic; silent transmission.

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Conflict of interest statement

The authors declare no competing interest.

Figures

Fig. 1.
Fig. 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram showing the numbers of studies screened and included in the meta-analysis.
Fig. 2.
Fig. 2.
Pooled percentage of laboratory-confirmed COVID-19 cases which remained asymptomatic. Studies that did not report follow-up of silent infections or failed to identify index cases were excluded from the analysis.
See this image and copyright information in PMC

Comment in

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