COVID-19, Myocarditis and Pericarditis

Abstract

Viral infections are a leading cause of myocarditis and pericarditis worldwide, conditions that frequently coexist. Myocarditis and pericarditis were some of the early comorbidities associated with SARS-CoV-2 infection and COVID-19. Many epidemiologic studies have been conducted since that time concluding that SARS-CoV-2 increased the incidence of myocarditis/pericarditis at least 15× over pre-COVID levels although the condition remains rare. The incidence of myocarditis pre-COVID was reported at 1 to 10 cases/100 000 individuals and with COVID ranging from 150 to 4000 cases/100 000 individuals. Before COVID-19, some vaccines were reported to cause myocarditis and pericarditis in rare cases, but the use of novel mRNA platforms led to a higher number of reported cases than with previous platforms providing new insight into potential pathogenic mechanisms. The incidence of COVID-19 vaccine-associated myocarditis/pericarditis covers a large range depending on the vaccine platform, age, and sex examined. Importantly, the findings highlight that myocarditis occurs predominantly in male patients aged 12 to 40 years regardless of whether the cause was due to a virus-like SARS-CoV-2 or associated with a vaccine—a demographic that has been reported before COVID-19. This review discusses findings from COVID-19 and COVID-19 vaccine-associated myocarditis and pericarditis considering the known symptoms, diagnosis, management, treatment, and pathogenesis of disease that has been gleaned from clinical research and animal models. Sex differences in the immune response to COVID-19 are discussed, and theories for how mRNA vaccines could lead to myocarditis/pericarditis are proposed. Additionally, gaps in our understanding that need further research are raised.

Response by Yonker et al to Letter Regarding Article, “Circulating Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis”

“…Alternatively, it has been hypothesized that spike protein antigenemia may activate resident mast cells or macrophages, which then leads to myocarditis. 6 We did not see any evidence of viral reactivation or autoimmunity in our cohort.…”

COVID-19 and the Cardiovascular System: Requiem for a Medical Minotaur

“…Although heightened surveillance and diagnosis relying on clinical symptoms and elevated troponins rather than endomyocardial biopsy may account for some increased incidence of myocarditis with SARS-CoV-2 infection, in some reports the incidence of myocarditis/pericarditis during the COVID-19 era is as much as 15-fold higher when compared with myocarditis in the preCOVID-19 era. Nevertheless, as noted by Fairweather et al, 7 the incidence of myocarditis based on tissue diagnosis is lower than in initial reports. Regardless of the etiology of myocardial injury, its relatively common occurrence in COVID-19 may lead to long-term consequences, including a higher associations of subsequent cardiovascular events.…”

“…Similar trends are observed with pericarditis also occurring more often in males. Fairweather, et al, 7 propose potential mechanisms of how sex differences might be explained using animal models, some of which may involve the TLR4 (toll-like receptor 4)/IL-1R (interleukin 1 receptor)/ST2 (Suppression Of Tumorigenicity 2) signaling axis in mast cell and macrophages. On the other hand, Altman, et al 9 place the issue of mRNA vaccine-associated myocarditis and myocardial injury in the contexts of non-SARS-CoV-2-invoked myocarditis, myocardial injury associated with COVID-19 infection, and myocarditis associated with non-COVID-19 vaccines.…”

“…Several points emerge from this analysis. First, only a relatively small minority of patients thought to have myocarditis presenting contemporaneously with COVID-19 infection have histological evidence of inflammation (7% in autopsy studies, 4,7 and 11% by endomyocardial biopsy. 5,10,11 On histopathology a low incidence of inflammatory infiltrate is also found in patients diagnosed with post mRNA vaccine myocarditis.…”

“…In addition to the early reports of thrombotic outcomes in COVID-19 patients, evidence of myocardial injury, myocarditis, and pericarditis became apparent. Fairweather et al 7 note that SARS-CoV-2 infection is not unique in its impact on myocarditis and that the prior coronavirus infections SARS-CoV-1 and Middle-Eastern Respiratory syndrome (MERS-CoV-1) have also been associated with myocardial inflammation. Although heightened surveillance and diagnosis relying on clinical symptoms and elevated troponins rather than endomyocardial biopsy may account for some increased incidence of myocarditis with SARS-CoV-2 infection, in some reports the incidence of myocarditis/pericarditis during the COVID-19 era is as much as 15-fold higher when compared with myocarditis in the preCOVID-19 era.…”