Effectiveness of influenza vaccination to prevent severe disease: a systematic review and meta-analysis of test-negative design studies.

Background: Seasonal influenza vaccination may be effective against severe influenza disease.

Objectives: To assess evidence on the real-world effectiveness of influenza vaccination in preventing severe influenza-related outcomes.

Data sources: PubMed, Ovid, and Cochrane CENTRAL from inception to September 24, 2024.

Study eligibility criteria: Observational test-negative design studies reporting influenza vaccine effectiveness (IVE) against influenza-associated hospitalisation, death, pneumonia, intensive care unit (ICU) admission, or ventilatory support (VS).

Participants: Hospitalized adults and children with laboratory-confirmed influenza and inpatient controls who tested negative for influenza infection.

Interventions: Influenza vaccination.

Assessment of risk of bias: Newcastle-Ottawa Scale (NOS) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were used to assess study quality and evidence certainty.

Methods of data synthesis: We extracted study characteristics and odds ratio (OR) or IVE estimates and corresponding 95% confidence intervals (95% CI). Both crude and adjusted estimates were considered and analysed using a random-effects model. We calculated pooled IVE overall and by season, age group, circulating strains, vaccine type and match between vaccine and circulating strains.

Results: Overall, 7727 publications were identified, 461 reviewed, 165 included. Pooled IVE was 42% (95% CI 39-44) against influenza-associated hospitalisation (very low certainty), 36% (95% CI 24-46) against death (no certainty), 51% (95% CI 36-63) against pneumonia (low certainty), 52% (95% CI 38-63) against ICU admission (very low certainty), and 55% (95% CI 44-64) against VS (low certainty). IVE varied by age and was generally higher (up to 2-fold) in children compared to adults. Higher IVE was observed against influenza A(H1N1) compared to A(H3N2) and in seasons with good vaccine match. Hospitalisation IVE was slightly higher for quadrivalent (45% (95% CI, 32-56) compared to trivalent (36% (95% CI, 27-43) vaccine.

Conclusions: Seasonal influenza vaccination moderately reduces severe influenza-related outcomes, particularly in children, against A(H1N1), and with good vaccine-strain match.

Prospero registration: CRD42023476003.