Induction of trained immunity by influenza vaccination - impact on COVID-19

TLDR

Certain vaccines exhibit non‑specific protective effects via trained immunity, and epidemiological studies suggest influenza vaccination may cross‑protect against COVID‑19. The quadrivalent inactivated influenza vaccine induces trained immunity, reprogramming monocytes and reducing systemic inflammation, thereby enhancing innate antiviral responses. In a Dutch hospital, influenza‑vaccinated employees had 37 % and 49 % lower SARS‑CoV‑2 infection rates in the first and second COVID‑19 waves, supporting a protective effect that warrants randomized trials.

Abstract

Non-specific protective effects of certain vaccines have been reported, and long-term boosting of innate immunity, termed trained immunity, has been proposed as one of the mechanisms mediating these effects. Several epidemiological studies suggested cross-protection between influenza vaccination and COVID-19. In a large academic Dutch hospital, we found that SARS-CoV-2 infection was less common among employees who had received a previous influenza vaccination: relative risk reductions of 37% and 49% were observed following influenza vaccination during the first and second COVID-19 waves, respectively. The quadrivalent inactivated influenza vaccine induced a trained immunity program that boosted innate immune responses against various viral stimuli and fine-tuned the anti-SARS-CoV-2 response, which may result in better protection against COVID-19. Influenza vaccination led to transcriptional reprogramming of monocytes and reduced systemic inflammation. These epidemiological and immunological data argue for potential benefits of influenza vaccination against COVID-19, and future randomized trials are warranted to test this possibility.