The role of asymptomatic SARS-CoV-2 infections: rapid living systematic review and meta-analysis

Abstract

OBJECTIVE To address three questions: 1. amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? 2. Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? 3. What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection, or pre-symptomatic? DESIGN Rapid living systematic review and meta-analysis. DATA SOURCES PubMed, Embase, bioRxiv and medRxiv using a living evidence database of SARS-CoV-2 literature, searched on 25 March 2020 and updated on 20 April 2020. STUDY SELECTION Studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR that documented follow-up and symptom status at the beginning and end of follow-up or modelling studies. DATA EXTRACTION One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias was assessed with an adapted checklist for case series and a questionnaire to assess relevance and credibility of modelling studies. RESULTS We screened 315 records and included 37. The overall estimate of the proportion of people who become infected with SARS-CoV-2 and remain asymptomatic throughout infection was 15% (95% CI 10 to 22%) with a prediction interval of 3 to 55% in 28 studies that addressed this review question. There was some evidence that bias in the selection of participants influences the outcome. The proportion of people that is pre-symptomatic could not be summarised, owing to heterogeneity. In modelling studies, 40-60% of all SARS-CoV-2 infections are the result of transmission from pre-symptomatic individuals, with a smaller contribution from asymptomatic individuals. CONCLUSION An intermediate contribution of pre-symptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention measures, with enhanced hand and respiratory hygiene, testing tracing and isolation strategies and social distancing, will continue to be needed. The findings of this living systematic review of publications early in the pandemic suggests that most SARS-CoV-2 infections are not asymptomatic throughout the course of infection.