Myocarditis following COVID-19 vaccination: incidence, mechanisms, and clinical considerations

Abstract

Introduction Vaccines have demonstrated protection against the morbidity and mortality of COVID-19, but concerns regarding the rare side effect of acute myocarditis have stymied immunization efforts. This review aims to describe the incidence and theorized mechanisms of COVID vaccine-associated myocarditis and review relevant principles for management of vaccine-associated myocarditis Areas covered Epidemiologic studies of myocarditis after COVID vaccination are reviewed, which show an incidence of approximately 20–30 per million patients. The vast majority of these cases are seen with mRNA vaccines especially in male patients under 30 years of age. Mechanisms are largely theoretical, but molecular mimicry and dysregulated innate immune reactions have been proposed. While studies suggest that this subtype of myocarditis is mild and self-limited, long-term evidence is lacking. Principles of myocarditis treatment and surveillance are outlined as they apply to COVID vaccine-associated myocarditis. Expert Opinion COVID vaccine-associated myocarditis is rare but well described in certain at-risk groups. Better understanding of its pathogenesis is key to mitigating this complication and advancing vaccination efforts. Risk-benefit analyses demonstrate that individual- and population-level benefits of vaccination exceed the risks of this rare and mild form of myocarditis.

Cardiovascular Manifestation of the BNT162b2 mRNA COVID-19 Vaccine in Adolescents

“…The potential mechanism of mRNA COVID-19 vaccine-induced myocarditis remains unknown. It has been suggested that excessive innate immune activation by both lipid nanoparticle and RNA components of COVID-19 vaccines can cause myocarditis [24,25]. Endosomal toll-like receptor (TLR) TLR3, TLR7, and TLR8 in immune cells and RIG-I and MDA5 in nonimmune cells act as a natural defense against foreign RNA but can crossreact with in vitro transcribed (IVT) RNA [26].…”

“…Endosomal toll-like receptor (TLR) TLR3, TLR7, and TLR8 in immune cells and RIG-I and MDA5 in nonimmune cells act as a natural defense against foreign RNA but can crossreact with in vitro transcribed (IVT) RNA [26]. The activation of these receptors triggers an inflammatory cascade, assembly of inflammasome platform production of type I interferons, and nuclear translocation of NK-kB [24,25,27]. Inflammasomes are large multiproteins that are responsive to pathogen-and stress-associated cellular insults.…”

New insights into human immune memory from SARS‐CoV‐2 infection and vaccination

“… 123 Importantly, these complications are now well documented, and can be recognized and treated early to avoid long‐term complications. 126 , 127 , 128 , 129 …”

“…Myocarditis following mRNA vaccination is more prominent in young men with 1.7 in 100,000 affected 123 . Importantly, these complications are now well documented, and can be recognized and treated early to avoid long‐term complications 126–129 …”

Post-COVID mRNA vaccine myocarditis in children: report of two cases

“…Studies from the USA show that the risk of myocarditis after receiving mRNA-based COVID-19 vaccines is increased across all age and sex groups. Epidemiological studies reported an incidence of 20–30 per million patients, and the risk is highest after the second vaccination dose in adolescent males 2 3. The Centers for Disease Control and Prevention (CDC) recommends that COVID-19 primary series vaccines should be given to everyone aged 6 months and older with COVID-19 boosters for everyone 5 years and older 4.…”