Asymptomatic norovirus infection during outbreaks in China: A systematic review and meta-analysis

Acute gastroenteritis outbreaks may be caused by the excretion of norovirus (NoV) from asymptomatic individuals. Despite numerous studies involving asymptomatic NoV infection during outbreaks in China, a comprehensive assessment of its role has not been conducted, which is critical for emergency management. Our objective was to assess the prevalence of asymptomatic NoV infection during outbreaks in China. We conducted a comprehensive search of multiple databases, including PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, China Wanfang, and China Weipu, between January 1, 1997 and June 19, 2023. The retrieved articles and their references underwent screening, which utilized polymerase chain reaction-based assays for the detection of NoV in asymptomatic individuals during outbreaks that occurred in China. The primary summary data were the prevalence of asymptomatic NoV infection in outbreaks. We generated pooled estimates of asymptomatic prevalence in the population as a whole and in subgroups by using random-effect models. Of the 97 articles included, the pooled asymptomatic prevalence of NoV among 5117 individuals in outbreaks was 17.6% (95% confidence interval [CI]: 14.1-21.3). The asymptomatic prevalence of NoV GII (17.1%, 95% CI: 12.9-21.5) was similar to that of NoV GI (22.0%, 95% CI: 12.8-32.4). However, the proportion of asymptomatic individuals involved in NoV GII (57.44%) was significantly higher than that of NoV GI (5.12%), and NoV GII (75.26%) was reported much more frequently than NoV GI (14.43%) in the included articles. Meta-regression analysis of 11 possible influencing factors (geographic region, setting, season, sample type, genotype, transmission route, occupation, age, per capita income, study quality, and cases definition) showed that the source of heterogeneity might be related to the outbreak settings, per capita income, and study quality (p = 0.037, 0.058, and 0.026, respectively). Of particular note was the asymptomatic prevalence peaked in preschoolers (27.8%), afterward, it fell into trough in elementary and junior school children (10.5%), before the second peak located in adults (17.8%), and the elderly (25.2%). Prevalent genotypes reported include GII.4, followed by GII.17, GII.2, GII.3, GII.6, and so forth. The estimated asymptomatic prevalence of NoV during outbreaks in China was as high as 17.6%, with NoV GII dominating. In addition, genetic subtypes of NoV in outbreaks should be detected whenever possible. The role of asymptomatic individuals in NoV outbreaks cannot be ignored. This knowledge will help governments develop public health policies and emergency response strategies for outbreaks, assess the burden, and develop vaccines.