期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：34
DOI：10.1073/pnas.2109229118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Asymptomatic infections have been widely reported for COVID-19. However, many studies do not distinguish between the presymptomatic stage and truly asymptomatic infections. We conducted a systematic review and meta-analysis of COVID-19 literature reporting laboratory-confirmed infections to determine the burden of asymptomatic infections and removed index cases from our calculations to avoid conflation. By analyzing over 350 papers, we estimated that more than one-third of infections are truly asymptomatic. We found evidence of greater asymptomaticity in children compared with the elderly, and lower asymptomaticity among cases with comorbidities compared to cases with no underlying medical conditions. Greater asymptomaticity at younger ages suggests that heightened vigilance is needed among these individuals, to prevent spillover into the broader community.
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.
