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

Debisarun, P. A.; Gössling, K. L.; Bulut, O.; Kilic, G.; Zoodsma, M.; Liu, Z.; Oldenburg, M.; Rüchel, N.; Zhang, B.; Xu, C.-J.; Struycken, P.; Koeken, V. A. C. M.; Dominguez-Andres, J.; Moorlag, S. J. C. F. M.; Taks, E.; Ostermann, P. N.; Müller, L.; Schaal, H.; Adams, O.; Borkhardt, A.; ten Oever, J.; van Crevel, R.; Li, Y.; Netea, M.

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.