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

Priya A Debisarun,Ortwin Adams,Heiner Schaal,Jaap Ten Oever,Zhaoli Liu,Katharina L Gössling,Martijn Zoodsma,Bowen Zhang,Marina Oldenburg,Lisa Müller,Reinout Van Crevel,Esther Taks,Nadine Rüchel,Arndt Borkhardt,Yang Li,Mihai G Netea,Valerie A C M Koeken,Özlem Bulut ,Jorge Domínguez‐Andrés ,Gizem Kılıç ,P.m Struycken ,Simone J.c.f.m Moorlag ,Philipp Niklas Ostermann ,Cheng‐Jian Xu

doi:10.1371/journal.ppat.1009928

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.

Highlights

As of May 2021, over 150 million cases and 3.1 million deaths due to the novel coronavirus disease COVID-19 have been reported [1]
Quadrivalent inactivated influenza vaccination is associated with lower COVID-19 incidence
To investigate the effect of influenza vaccination on COVID-19 incidence, we compared the incidence of COVID-19 cases, validated by SARS-CoV-2 PCR, among hospital workers who were either vaccinated or not against influenza

Summary

Introduction

As of May 2021, over 150 million cases and 3.1 million deaths due to the novel coronavirus disease COVID-19 have been reported [1]. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While in the majority of cases the virus causes mild symptoms that resolve spontaneously, in the elderly or patients with underlying co-morbidities, the disease is often severe and potentially lethal [2]. Several effective anti-COVID-19 vaccines have been designed and successfully tested, with almost 1 billion vaccine doses already administered [1]. Vaccine supply is still not able to ensure the global needs, with many countries facing challenges in ensuring access to enough COVID-19 vaccines [5]. An additional challenge is the emergence of new SARSCoV-2 variants which are on the one hand more infective, and on the other hand can display vaccine escape [6]

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