Abstract
Background: Cross-sectional studies indicate that up to 80% of active SARS-CoV-2 infections may be asymptomatic. However, accurate estimates of the asymptomatic proportion require systematic detection and follow-up to differentiate between truly asymptomatic and pre-symptomatic cases. We conducted a rapid review and meta-analysis of the asymptomatic proportion of PCR-confirmed SARS-CoV-2 infections based on methodologically appropriate studies in community settings. Methods: We searched Medline and EMBASE for peer-reviewed articles, and BioRxiv and MedRxiv for pre-prints published before 25/08/2020. We included studies based in community settings that involved systematic PCR testing on participants and follow-up symptom monitoring regardless of symptom status. We extracted data on study characteristics, frequencies of PCR-confirmed infections by symptom status, and (if available) cycle threshold/genome copy number values and/or duration of viral shedding by symptom status, and age of asymptomatic versus (pre)symptomatic cases. We computed estimates of the asymptomatic proportion and 95% confidence intervals for each study and overall using random effect meta-analysis. Results: We screened 1138 studies and included 21. The pooled asymptomatic proportion of SARS-CoV-2 infections was 23% (95% CI 16%-30%). When stratified by testing context, the asymptomatic proportion ranged from 6% (95% CI 0-17%) for household contacts to 47% (95% CI 21-75%) for non-outbreak point prevalence surveys with follow-up symptom monitoring. Estimates of viral load and duration of viral shedding appeared to be similar for asymptomatic and symptomatic cases based on available data, though detailed reporting of viral load and natural history of viral shedding by symptom status were limited. Evidence into the relationship between age and symptom status was inconclusive. Conclusion: Asymptomatic viral shedding comprises a substantial minority of SARS-CoV-2 infections when estimated using methodologically appropriate studies. Further investigation into variation in the asymptomatic proportion by testing context, the degree and duration of infectiousness for asymptomatic infections, and demographic predictors of symptom status are warranted.
Highlights
Reports of asymptomatic SARS-CoV-2 infection and potential transmission1–3 have generated concern regarding the implications of undetected asymptomatic transmission on the effectiveness of public health interventions in the current COVID-19 pandemic4
While asymptomatic viral shedding has been suggested to comprise up to ~80% of SARS-CoV-2 infections6–8, data informing these figures are largely confined to cross-sectional reports that cannot distinguish truly asymptomatic cases from those who are pre-symptomatic at the point of testing
Selection criteria We included studies that met all of the following criteria: 1) human study; AND 2) presented original research or public health COVID-19 surveillance data; AND 3) available in English; AND 4) presented data on polymerase chain reaction (PCR) confirmed COVID-19 cases; AND 5) presented data on PCR testing of exposed or potentially exposed individuals regardless of symptom status; AND 6) had systematic follow-up at ≥ 1 time-point and reporting of symptom status among PCR confirmed cases; AND 7) presented data from a community setting
Summary
Reports of asymptomatic SARS-CoV-2 infection and potential transmission have generated concern regarding the implications of undetected asymptomatic transmission on the effectiveness of public health interventions in the current COVID-19 pandemic. While asymptomatic viral shedding has been suggested to comprise up to ~80% of SARS-CoV-2 infections, data informing these figures are largely confined to cross-sectional reports that cannot distinguish truly asymptomatic cases from those who are pre-symptomatic at the point of testing (see Figure 1). Interchangeable use of these concepts, i.e. asymptomatic and pre-symptomatic, precludes accurate estimation of the asymptomatic proportion of potentially infectious SARS-CoV-2 cases. We extracted data on study characteristics, frequencies of PCR-confirmed infections by symptom status, and (if available) cycle threshold/genome copy number values and/or duration of viral shedding by symptom status, and age of asymptomatic versus (pre)symptomatic cases. Estimates of viral load and duration of Invited Reviewers 1 version 1
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