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Oran DP, Topol EJ. The Proportion of SARS-CoV-2 Infections That Are Asymptomatic : A Systematic Review. Ann Intern Med. 2021 Jan 22:M20-6976. doi: 10.7326/M20-6976. Epub ahead of print. PMID: 33481642; PMCID: PMC7839426.

Background: Asymptomatic infection seems to be a notable feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), but the prevalence is uncertain.

Purpose: To estimate the proportion of persons infected with SARS-CoV-2 who never develop symptoms.

Data sources: Searches of Google News, Google Scholar, medRxiv, and PubMed using the keywords antibodies, asymptomatic, coronavirus, COVID-19, PCR, seroprevalence, and SARS-CoV-2.

Study selection: Observational, descriptive studies and reports of mass screening for SARS-CoV-2 that were either cross-sectional or longitudinal in design; were published through 17 November 2020; and involved SARS-CoV-2 nucleic acid or antibody testing of a target population, regardless of current symptomatic status, over a defined period.

Data extraction: The authors collaboratively extracted data on the study design, type of testing performed, number of participants, criteria for determining symptomatic status, testing results, and setting.

Data synthesis: Sixty-one eligible studies and reports were identified, of which 43 used polymerase chain reaction (PCR) testing of nasopharyngeal swabs to detect current SARS-CoV-2 infection and 18 used antibody testing to detect current or prior infection. In the 14 studies with longitudinal data that reported information on the evolution of symptomatic status, nearly three quarters of persons who tested positive but had no symptoms at the time of testing remained asymptomatic. The highest-quality evidence comes from nationwide, representative serosurveys of England (n = 365 104) and Spain (n = 61 075), which suggest that at least one third of SARS-CoV-2 infections are asymptomatic.

Limitation: For PCR-based studies, data are limited to distinguish presymptomatic from asymptomatic infection. Heterogeneity precluded formal quantitative syntheses.

Conclusion: Available data suggest that at least one third of SARS-CoV-2 infections are asymptomatic. Longitudinal studies suggest that nearly three quarters of persons who receive a positive PCR test result but have no symptoms at the time of testing will remain asymptomatic. Control strategies for COVID-19 should be altered, taking into account the prevalence and transmission risk of asymptomatic SARS-CoV-2 infection.

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