To estimate associations between trivalent influenza vaccination and COVID-19 mortality as well as severe clinical outcomes among hospitalised patients.

Retrospective observational study.

This study was conducted among hospitalised patients with COVID-19 in Brazil.

We analysed all hospitalised patients with COVID-19 with available vaccination information captured in Brazil’s national electronic respiratory infection data system between 1 January 2020 and 23 June 2020.

The primary outcomes were age-specific mortality rates of hospitalised patients with COVID-19 with and without recent inactivated trivalent influenza vaccination.

A total of 53 752 clinically confirmed COVID-19 cases were analysed. Controlling for health facility of treatment, comorbidities as well as an extensive range of sociodemographic factors, patients who received a recent influenza vaccine experienced on average 7% lower odds of needing intensive care treatment (95% CI 0.87 to 0.98), 17% lower odds of requiring invasive respiratory support (95% CI 0.77 to 0.88) and 16% lower odds of death (95% CI 0.78 to 0.90). Protective effects were larger when the vaccine was administered after onset of symptoms as well as among younger patients.

Patients with COVID-19 with recent inactivated influenza vaccination experience significantly better health outcomes than non-vaccinated patients in Brazil. Beneficial off-target effects of influenza vaccination through trained innate immune responses seem plausible and need to be further explored. Large-scale promotion of influenza vaccines seems advisable, especially in populations at high risk for severe COVID-19 disease progression.