RESUMO
During the COVID-19 pandemic, large differences in susceptibility and mortality due to SARS-CoV-2 infection have been reported between populations in Europe and South Asia. While both host and environmental factors (including BCG vaccination) have been proposed to explain this, the potential biological substrate of these differences is unknown. We purified peripheral blood mononuclear cells from individuals living in India and the Netherlands at baseline and 10-12 weeks after BCG vaccination. We compared chromatin accessibility between the two populations at baseline, as well as gene transcription profiles and cytokine production capacities upon viral stimulation with influenza and SARS-CoV-2. The chromatin accessibility of genes important for adaptive immunity was higher in Indians compared to Europeans, while the latter had more accessible chromatin regions in genes of the innate immune system. At the transcriptional level, we observed that Indian volunteers displayed a more tolerant immune response to viral stimulation, in contrast to a more exaggerated response in Europeans. BCG vaccination strengthened the tolerance program in Indians, but not in Europeans. These differences may partly explain the different impact of COVID-19 on the two populations.
RESUMO
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.
RESUMO
Every year, influenza causes 290.000 to 650.000 deaths worldwide and vaccination is encouraged to prevent infection in high-risk individuals. Interestingly, cross-protective effects of vaccination against heterologous infections have been reported, and long-term boosting of innate immunity (also termed trained immunity) has been proposed as the underlying mechanism. Several epidemiological studies also suggested cross-protection between influenza vaccination and COVID-19 during the current pandemic. However, the mechanism behind such an effect is unknown. Using an established in-vitro model of trained immunity, we demonstrate that the quadrivalent inactivated influenza vaccine used in the Netherlands in the 2019-2020 influenza season can induce a trained immunity response, including an improvement of cytokine responses after stimulation of human immune cells with SARS-CoV-2. In addition, we found that SARS-CoV-2 infection was less common among Dutch hospital employees who had received influenza vaccination during the 2019/2020 winter season (RR = 0,61 (95% CI, 0.4585 - 0.8195, P = 0.001). In conclusion, a quadrivalent inactivated influenza vaccine can induce trained immunity responses against SARS-CoV-2, which may result in relative protection against COVID-19. These data, coupled with similar recent independent reports, argue for a beneficial effect of influenza vaccination against influenza as well as COVID-19, and suggests its effective deployment in the 2020-2021 influenza season to protect against both infections.
