Myocarditis and pericarditis in COVID-19 vaccine recipients

Are the cardiac complications associated with the coronavirus disease 2019 (COVID-19) vaccines worse than the disease itself? In order to answer this question, it is necessary to understand their true incidence and association with the vaccine.

A new study published on the preprint server medRxiv* provides valuable evidence towards this end, using surveillance data to provide the best estimates of these outcomes.

Study: Myocarditis and Pericarditis following COVID-19 Vaccination:  Evidence Syntheses on Incidence, Risk Factors, Natural History, and Hypothesized Mechanisms. Image Credit: /

Study: Myocarditis and Pericarditis following COVID-19 Vaccination:  Evidence Syntheses on Incidence, Risk Factors, Natural History, and Hypothesized Mechanisms. Image Credit: /


The onset of COVID-19, caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to a worldwide outbreak of infections, sickness, and death. The emergence and rapid transmission of SARS-CoV-2 prompted the development of vaccines to potentially create herd immunity and limit the spread of SARS-CoV-2.

However, doubts raised by the unprecedented speed of vaccine approval, the novel platforms used for their development, and the rapid spread of conspiracy theories, accompanied by a severe shortfall of vaccine supplies to developing areas of the world, hindered the expected speed of vaccine coverage. During this lag period, attention shifted to the potential adverse effects associated with COVID-19 vaccines.

The cardiac events following COVID-19 vaccination have been of particular concern, including myocarditis and pericarditis. The current study summarizes the results of an analysis of more than 8,000 cases of these complications while presenting a possible mechanism by which they arise.

The first reports of myocarditis and pericarditis arose in April 2021 and triggered the development of a system to monitor these and other events of special interest occurring subsequent to vaccination with a nucleic acid or messenger ribonucleic acid (mRNA) vaccine from either Pfizer or Moderna. Currently, myocarditis occurs in 1-2, and 11, cases per 100,000 person-years, in the United States and the United Kingdom, respectively.

Conversely, the rates in these countries after vaccination are 1.4 and 0.2 per million, respectively. In both situations, myocarditis is more common in young males.

Study findings

The scientists included systematic reviews, evidence reviews, and evidence underpinning proposed mechanisms. An earlier review by the same authors showed negligible rates of myocarditis and pericarditis after vaccines other than the mRNA vaccines and in adults aged 40 years or over. With mRNA vaccines, there were differences in the incidence of myocarditis in different age groups, as well as vaccine dosage, and between sexes.

In the present study, 14 studies were reviewed, all of which came from several mostly Westernized developed countries. The results showed that in females of any age and in children aged 5-11 years old of either sex, myocarditis occurred in less than 20 cases per million after the second dose of the Pfizer vaccine. However, this side effect occurred in 25-82 per million male adults between 18-39 years of age; however, doubts on this estimate remain.

The third vaccine dose was followed by myocarditis in less than 20 cases per million in adults aged 40 years and over. There is little certainty about the incidence of this side effect in females of this age, as well as in individuals between 13 and 39 years of age.

Pericarditis is covered in very little detail; therefore, its incidence after Pfizer vaccination remains uncertain.

The Moderna vaccine provides a higher dose of the spike antigen than the Pfizer vaccine and is likely associated with a higher incidence of myocarditis in males and females aged 18-29 years and in males alone aged 18-39 years. In older adults, there is little difference.

The risk of these events may be lowered by increasing the interval between doses to at least 31 days. An interval of 56 days or more, for example, may be most beneficial in young males between the ages of 18-29 years in reducing the incidence.

Children were more likely to present with myocarditis presented with symptoms after receiving their second dose. Notably, almost all children recovered from this side effect.

Over 90% of myocarditis cases after vaccination were reported in males aged 20-29 years, though the youngest was 12 and the oldest 56 years old. The average lag from the last dose to the onset of symptoms was two to four days, with common symptoms including chest pain, pressure, or increases in troponin.

Heart dysfunction was observed in less than a third of patients. Although 84% of heart dysfunction cases were hospitalized, intensive care unit admission was uncommon, with most patients being discharged within two to four days. Mortality was less than 1% among unconfirmed patients and less than 2% among unconfirmed cases.

Pericarditis was mentioned in three reports, the vast majority of which were unconfirmed and mostly in males. The median interval from the last vaccine dose to symptom onset was 20 days, mostly after the second dose. Hospitalizations occurred in between 30% to 70% of cases but rarely required intensive care unit (ICU) admission, with the median length of stay being one day and mortality occurring in less than 0.5% of cases.

The mechanisms of cardiac inflammation following COVID-19 mRNA vaccination included autoimmunity, serum sickness, hypersensitivity to one or more components of the vaccine, low levels of double-stranded RNA, increased blood viscosity leading to heart inflammation, and inflammation induced by heavy exercise. Sex steroids were often implicated by researchers to account for the male-female divide.


The highest risk of vaccine-associated myocarditis is in young adults and adolescents at a rate of up to 140 per million. Children between five and 11 years of age, as well as females of all ages, are at low risk. The Moderna vaccine may be linked to a higher incidence of myocarditis as compared to Pfizer in adults between 18 and 29 years of age.

In males who are between 18 and 29 years of age, increasing the interval between the first and second doses to at least eight weeks resulted in a significant reduction in the incidence of myocarditis. Overall, there is little data on long-term outcomes, though the illness appears to resolve spontaneously, completely, and rapidly.

The various pathogenetic mechanisms all lack one or more convincing explanations. However, it remains true that myocarditis is mostly found in young males, who are nonetheless at small risk. Similarly, the illness is mostly mild and self-limiting. The use of the Pfizer vaccine may reduce the risk in this subgroup still further, especially if the intervals between doses are increased.

The understanding that myocarditis is far more common, serious, and damaging following COVID-19 as compared to vaccination should be clearly communicated to young males and their caregivers, guardians, or parents. Furthermore, this patient population should be given information on the proven ability of vaccines to reduce the clinical severity and mortality rate of COVID-19, as it may facilitate and encourage proper decision-making.

Ongoing surveillance of adverse vaccine effects is key to shaping future strategies for booster doses, especially as SARS-CoV-2 continues to mutate. Myocarditis patients should be closely monitored to identify and trace long-term sequelae if any.

A mechanistic understanding of this complication will require multiple centers to be involved in carrying out prospective studies.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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