The Fraction of Influenza Virus Infections That Are Asymptomatic A Systematic Review and Meta-analysis

Background: The fraction of persons with influenza virus infection, who do not report any signs or symptoms throughout the course of infection is referred to as the asymptomatic fraction. Methods: We conducted a systematic review and meta-analysis of published estimates of the asymptomatic fraction of influenza virus infections. We found that estimates of the asymptomatic fraction were reported from two different types of studies: first, outbreak investigations with short-term follow-up of potentially exposed persons and virologic confirmation of infections; second, studies conducted across epidemics typically evaluating rates of acute respiratory illness among persons with serologic evidence of infection, in some cases adjusting for background rates of illness from other causes. Results: Most point estimates from studies of outbreak investigations fell in the range 4%-28% with low heterogeneity (I-2 = 0%) with a pooled mean of 16% (95% confidence interval = 13%, 19%). Estimates from the studies conducted across epidemics without adjustment were very heterogeneous (point estimates 0%-100%; I (2) = 97%), while estimates from studies that adjusted for background illnesses were more consistent with point estimates in the range 65%-85% and moderate heterogeneity (I-2 = 58%). Variation in estimates could be partially explained by differences in study design and analysis, and inclusion of mild symptomatic illnesses as asymptomatic in some studies. Conclusions: Estimates of the asymptomatic fraction are affected by the study design, and the definitions of infection and symptomatic illness. Considerable differences between the asymptomatic fraction of infections confirmed by virologic versus serologic testing may indicate fundamental differences in the interpretation of these two indicators.