Global and national influenza-associated hospitalization and mortality rates: a systematic review and meta-analysis

BackgroundA global comprehensive assessment of influenza-associated hospitalization and mortality across diverse populations and geographical settings is currently lacking. To support an update of WHO influenza clinical guidelines, this systematic review and meta-analysis evaluated the baseline risks of hospitalization and all-cause mortality in patients with seasonal, pandemic, or zoonotic influenza. MethodsWe systematically searched Medline, Embase, CENTRAL, CINAHL, and Global Health for studies published through 26 October 2023, that reported hospitalization and/or mortality among patients with laboratory-confirmed influenza. Paired reviewers independently identified studies, extracted data, and assessed the risk of bias. We performed inverse variance method fixed effects model meta-analyses to summarize the evidence and evaluated the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. We registered the protocol with PROSPERO, CRD42023456645. FindingsOf 30054 records, 355 studies with 18,640,366 patients (mean age 0.1 to 87.9 years) proved eligible. The hospitalization rate was 1.01% (95%CI 1% to 1.01%; moderate certainty) for patients with seasonal or pandemic influenza and 93.72% (95%CI 90.12% to 96.58 %; low certainty) for patients with zoonotic influenza. The all-cause mortality rate was 0.23% (95%CI 0.22% to 0.24%; high certainty) for patients with non-severe seasonal or pandemic influenza, 4.15% (95%CI 4.10% to 4.20%; moderate certainty) for patients with severe seasonal or pandemic influenza, and 38.72% (95%CI 36.79% to 40.66%; moderate certainty) for patients with zoonotic influenza. InterpretationThis review estimated a hospitalization rate of 1.01% for seasonal or pandemic influenza and all-cause mortality rates of 0.23% for non-severe seasonal or pandemic influenza, 4.15% for severe seasonal or pandemic influenza, and 38.72% for severe zoonotic influenza. FundingWorld Health Organization to McMaster University in 2023. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSA comprehensive understanding of influenza-associated hospitalization and mortality rates is essential for guiding effective prevention and control strategies and formulating evidence-based clinical practice guidelines and policies. Previous systematic reviews and meta-analyses have investigated influenza-associated hospitalization and mortality rates, but they have often been limited by their focus on a specific strain of influenza, particular patient subgroups, or individual countries, or by a lack of assessment of the certainty of evidence. A global comprehensive assessment of influenza-associated hospitalization and mortality rates across diverse strains, populations, and geographical settings is currently lacking. Added value of this studyWe found a hospitalization rate of 1.01% for seasonal or pandemic influenza and all-cause mortality rates of 0.23% for non-severe seasonal or pandemic influenza, 4.15% for severe seasonal or pandemic influenza, and 38.72% for zoonotic influenza. Among severe seasonal or pandemic influenza cases, patients aged [≥]65 years (8.31%) had a higher all-cause mortality rate than those aged 0-14 years (0.76%) and 15-64 years (6.50%). Implications of all the available evidenceOur study provides a comprehensive assessment of the global evidence regarding hospitalization and mortality rates among influenza patients. Our findings highlight the critical need for distinct clinical and public health strategies tailored to influenza type and severity.