Effectiveness of influenza vaccines in preventing severe influenza illness among adults: A systematic review and meta-analysis of test-negative design case-control studies

•Studies estimating influenza vaccine effectiveness against laboratory-confirmed severe influenza often lead to imprecise results.•Seasonal influenza vaccines provided moderate protection against severe illness with laboratory confirmed influenza among adults of all ages.•Influenza vaccine effectiveness against influenza hospitalizations was lower among elderly compared to adults 18–64 years.•Low vaccine effectiveness against A(H3N2) was observed among elderly when vaccine and circulating strains were antigenically variant. Summary evidence of influenza vaccine effectiveness (IVE) against hospitalized influenza is lacking. We conducted a meta-analysis of studies reporting IVE against laboratory-confirmed hospitalized influenza among adults. We searched Pubmed (January 2009 to November 2016) for studies that used test-negative design (TND) to enrol patients hospitalized with influenza-associated conditions. Two independent authors selected relevant articles. We calculated pooled IVE against any and (sub)type specific influenza among all adults, and stratified by age group (18–64 and 65 years and above) using random-effects models. We identified 3411 publications and 30 met our inclusion criteria. Between 2010–11 and 2014–15, the pooled seasonal IVE was 41% (95%CI:34;48) for any influenza (51% (95%CI:44;58) among people aged 18–64y and 37% (95%CI:30;44) among ≥65 years). IVE was 48% (95%CI:37;59),37% (95%CI:24;50) and 38% (95%CI:23;53) against influenza A(H1N1)pdm09, A(H3N2) and B, respectively. Among persons aged ≥65 year, IVE against A(H3N2) was 43% (95%CI:33;53) in seasons when circulating and vaccine strains were antigenically similar and 14% (95%CI:-3;30) when A(H3N2) variant viruses predominated. Influenza vaccines provided moderate protection against influenza-associated hospitalizations among adults. They seemed to provide low protection among elderly in seasons where vaccine and circulating A(H3N2) strains were antigenically variant.