Impact of influenza vaccination on GP-diagnosed COVID-19 and all-cause mortality: a Dutch cohort study

Objectives: As clinical presentation and complications of both viruses overlap, it was hypothesised that influenza vaccination was associated with lower general practitioner (GP)-diagnosed COVID-19 rates and lower all-cause mortality rates.

Study design: From a primary care population-based cohort in the Netherlands, GP-diagnosed COVID-19 (between 10 March and 22 November 2020) and all-cause mortality events (between 30 December 2019 and 22 November 2020) were recorded. 223 580 persons were included, representing the influenza vaccination 2019 target group (all aged ≥60 years, and those <60 years with a medical indication). Proportional hazards regression analyses evaluated associations between influenza vaccination in 2019 and two outcomes: GP-diagnosed COVID-19 and all-cause mortality. Covariables were sex, age, comorbidities and number of acute respiratory infection primary care consultations in 2019.

Results: A slightly positive association (HR 1.15; 95% CI 1.08 to 1.22) was found between influenza vaccination in 2019 and GP-diagnosed COVID-19, after adjusting for covariables. A slightly protective effect for all-cause mortality rates (HR 0.90; 95% CI 0.83 to 0.97) was found for influenza vaccination, after adjusting for covariables. A subgroup analysis among GP-diagnosed COVID-19 cases showed no significant association between influenza vaccination in 2019 and all-cause mortality.

Conclusions: Our hypothesis of a possibly negative association between influenza vaccination in 2019 and GP-diagnosed COVID-19 was not confirmed as we found a slightly positive association. A slightly protective effect on all-cause mortality was found after influenza vaccination, possibly by a wider, overall protective effect on health. Future research designs should include test-confirmed COVID-19 cases and controls, adjustments for behavioural, socioeconomic and ethnic factors and validated cause-specific mortality cases.