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.

Immunogenicity, safety and consistency of seven lots of an inactivated COVID-19 vaccine in healthy children and adolescents: a randomized, double-blind, controlled, phase IV clinical trial.

Background: CoronaVac has been authorized worldwide for preventing coronavirus disease 2019. Information on the safety, immunogenicity and consistency of different lots and workshops of CoronaVac is presented here. Methods: In this randomized, double-blind, phase IV clinical trial in healthy children and adolescents aged 3-17 years, we aimed to assess the lot-to-lot and workshop-to-workshop consistency, as well as immunogenicity and safety of seven lots of commercial-scale CoronaVac from three workshops. Eligible participants were enrolled into three age cohorts (3-5, 6-11 and 12-17 years). Within each cohort, participants were randomly assigned to seven groups to receive two doses of CoronaVac, with four weeks apart. Serum samples were collected before the first dose and 28 days after the second dose for neutralizing antibody testing. The primary objective was to evaluate the consistency of immune response among different lots within workshop 2 or 3, as well as among different workshops. The primary endpoint was geometric mean titer (GMT) of neutralizing antibody at 28 days after full-course vaccination. Results: Between July 27th and November 19th, 2021, a total of 2,520 eligible participants were enrolled. Results showed that 95% confidence intervals (CIs) of GMT ratios for all comparative groups among different lots or workshops were within the equivalence criteria of [0.67, 1.5]. The GMT and seroconversion rate for all participants were 126.42 (95%CI: 121.82, 131.19) and 99.86% (95%CI: 99.59%, 99.97%) at 28 days after two-dose vaccination. The incidences of adverse reactions were similar among seven lots, and most adverse reactions were mild in Grade 1, with no serious adverse event. Conclusion: CoronaVac is well-tolerated and can elicit a good immune response among children and adolescents. Lot-to-lot consistency results indicate stable manufacturing of commercial-scale CoronaVac.