The immunomodulatory effects of exercise in viral and vaccine-associated myocarditis

Approximately five years ago, under the guidance of my supervisors, our research group initiated a series of experimental studies using the murine coxsackievirus B3 model to investigate the potential detrimental effects of physical exercise in the context of viral myocarditis. This line of research was instigated by clinical observations of professional athletes presenting with unexpected fibrotic scarring of the left ventricle—findings that led to the hypothesis that athletes may be particularly susceptible to developing myocardial fibrosis during (subclinical) viral infections (1, 2). Mechanistically, it was postulated that physical exercise might induce an altered immunological state, potentially exacerbating inflammatory and fibrotic processes within the myocardium. Preliminary studies conducted by my predecessor demonstrated that exercise training modulates the inflammatory response and promotes fibrotic remodeling in coxsackievirus-infected mice, providing initial experimental evidence in support of our hypothesis (3). Building on these findings, my doctoral research was designed to further investigate the interplay between physical exercise and cardiac immune responses in viral myocarditis. At the onset of my PhD, amid the COVID-19 pandemic, reports emerged of acute myocarditis following SARS-CoV-2 vaccination. This became a pressing public health concern and prompted urgent scientific investigation (4, 5). Leveraging the expertise and experimental framework established through our prior work on viral myocarditis, we expanded our research focus to investigate the mechanisms underlying this emerging phenomenon. At the time, the pathophysiology of SARS-CoV-2 mRNA vaccine-associated myocarditis remained poorly understood, in part due to the lack of robust experimental models. Concurrently, the predominance of acute myocarditis in young male individuals, along with anecdotal reports of cases of myocarditis in athletes following SARS-CoV-2 mRNA vaccination, raised concerns about the potential role of exercise in modulating cardiac immune responses to vaccination (6). As a result, the scope of my doctoral research evolved into a dual investigation of the immunomodulatory effects of exercise in both viral myocarditis and vaccine-associated myocardial injury.