Induction of trained immunity by influenza vaccination - impact on COVID-19
Priya A. Debisarun, Katharina L. Gössling, Özlem Bulut, Gizem Kılıç, Martijn Zoodsma, Zhaoli Liu, Marina Oldenburg, Nadine Rüchel, Bowen Zhang, Cheng‐Jian Xu, Patrick Struycken, Valerie A. C. M. Koeken, Jorge Domínguez‐Andrés, Simone J.C.F.M. Moorlag, Esther Taks, Philipp Niklas Ostermann, Lisa Müller, Heiner Schaal, Ortwin Adams, Arndt Borkhardt, Jaap ten Oever, Reinout van Crevel, Yang Li, Mihai G. Netea
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.