Risk factors for hospital admission and mortality in patients with influenza virus infection: a systematic review and meta-analysis.

Abstract

Identifying risk factors associated with hospital admission and mortality in patients with influenza is crucial for guiding clinical management and public health strategies. To support an update of WHO influenza clinical guidelines, this systematic review and meta-analysis assessed risk factors for hospital admission and all-cause mortality in patients with seasonal influenza. We systematically searched Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, and Global Health for observational studies published from Jan 1, 2000, until Oct 30, 2025, that enrolled patients of any age with laboratory-confirmed seasonal influenza and reported an adjusted effect estimate for the association between at least one risk factor and hospital admission or all-cause mortality, or both. We conducted inverse-variance random-effects model meta-analyses to summarise the evidence and assessed the certainty of evidence using the GRADE approach. We registered the protocol with PROSPERO, CRD42024535669. We identified 35 808 records, of which 63 studies enrolling 2 150 518 participants (mean age 3·6-87·9 years) were eligible. In patients with non-severe influenza, evidence with moderate or high certainty showed that older age (odds ratio 1·72 per 10-year increase for adults [95% CI 1·02-2·89]); cardiovascular disease (2·72 [1·24-5·94]); HIV, immunodeficiency, or immunosuppression (2·70 [1·55-4·70]); chronic respiratory disease (2·24 [1·90-2·64]); and any neurological disease (2·31 [1·65-3·24]) were major risk factors for hospital admission-pregnancy (1·88 [1·73-2·05]), diabetes (1·84 [1·26-2·67]), and malignancy (1·75 [1·12-2·75]) were additional risk factors for hospital admission. In patients with severe influenza, evidence with moderate or high certainty showed that secondary bacterial infection (4·13 [1·53-11·14]), malnutrition (3·29 [1·57-6·89]), sepsis (3·19 [2·08-4·89]), acute kidney injury (2·92 [1·11-7·73]), age 65 years or older (2·47 [2·21-2·75]), chronic cardiovascular disease (2·43 [1·16-5·09]), malignancy (2·21 [1·31-3·72]), and chronic neurological disease (2·08 [1·13-3·83]) were major risk factors for all-cause mortality-any liver disease (1·86 [1·35-2·58]); HIV, immunodeficiency, or immunosuppression (1·79 [1·51-2·13]), and chronic obstructive pulmonary disease (1·74 [1·37-2·20]) were additional risk factors for all-cause mortality. Age 65 years or older, immunocompromised status, cardiovascular disease, neurological disease, and chronic respiratory disease are major risk factors for hospital admission in patients with non-severe seasonal influenza. Secondary bacterial infection, malnutrition, sepsis, acute kidney injury, age 65 years or older, chronic cardiovascular disease, malignancy, and chronic neurological disease are major risk factors for all-cause mortality in patients with severe seasonal influenza. Our findings support risk stratification and targeted prevention and treatment strategies for seasonal influenza. WHO.