Heart Inflammation After mRNA Vaccines: Common Conditions Don’t Explain Young Men’s Risk

Young adult males who developed myocarditis or pericarditis after receiving an mRNA COVID-19 vaccine were no more likely to have had high blood pressure, diabetes, high cholesterol, or obesity than expected, according to a new analysis of US vaccine safety reports. In fact, these cardiovascular conditions appeared far less often among the reported cases than their known prevalence in the general population, leaving the question of why young men face elevated risk largely unanswered.

The study, published in the journal Drugs – Real World Outcomes, drew on the Vaccine Adverse Event Reporting System, or VAERS, a national US surveillance database jointly managed by the Centers for Disease Control and Prevention and the Food and Drug Administration. Researchers led by Mohammed Salah Salem, with Yola Moride and Bernard Bégaud, identified 869 reports of myocarditis or pericarditis following mRNA COVID-19 vaccination in males aged 18 to 30 years between 2021 and 2022. After excluding ten reports documenting a prior history of these heart conditions, 859 eligible reports remained for analysis.

Myocarditis and pericarditis are inflammatory conditions affecting the heart muscle and the protective membrane surrounding the heart, respectively. Rare cases following mRNA vaccination have been reported primarily among males under 30, and evidence from pharmacovigilance systems, cohort studies, and systematic reviews supports an association, with observational studies providing the strongest evidence for a causal link. The mechanisms behind this heightened susceptibility remain incompletely understood, though proposals include inflammatory and immune-mediated pathways, molecular mimicry, cross-reactivity, elevated free spike proteins, and genetic predisposition. What has been lacking, the authors note, is research into whether underlying medical conditions might modify this risk.

To probe that question, the team took an unusual methodological route. Observed-versus-expected and disproportionality analyses are staples of pharmacovigilance, typically used to detect safety signals for drugs and vaccines. Here, the researchers applied them to a different purpose: testing whether hypertension, diabetes, dyslipidemia, and obesity were disproportionately represented among reported myocarditis and pericarditis cases compared with vaccinated and general populations. The authors describe this as the first application of a disproportionality-based approach within a spontaneous reporting database to investigate potential risk modifiers of vaccine-related adverse events through pre-existing comorbidities.

The observed prevalence of the four conditions among the 859 cases was strikingly low. Hypertension appeared in 0.35 percent of reports, diabetes in 0.58 percent, dyslipidemia in 0.81 percent, and obesity in 1.75 percent. The researchers compared these figures against expected prevalence estimates drawn from a targeted literature review covering studies published between 2016 and 2022, including research on vaccinated US populations and prepandemic national statistics. Those sources painted a very different picture: diagnosed diabetes among 20-to-39-year-olds was estimated at 4.4 percent, obesity at 39.9 percent, hypertension among males aged 18 to 39 at 31.2 percent, and dyslipidemia among males aged 20 to 79 at 29.5 percent. Across every comorbidity, the observed rates in VAERS reports fell well below what these population estimates would predict.

The disproportionality analyses compared the myocarditis and pericarditis reports against three internal VAERS comparator groups: males aged 18 to 30 with other adverse event reports following mRNA COVID-19 vaccination, those with adverse event reports following non-COVID-19 vaccination, and those with Bell’s palsy reports following mRNA vaccination. Here the picture grew more nuanced. Myocarditis and pericarditis reports showed significantly higher rates of dyslipidemia, 0.81 percent versus 0.33 percent, and obesity, 1.75 percent versus 0.85 percent, but lower hypertension, 0.35 percent versus 1.30 percent, compared with other mRNA vaccine adverse event reports. Against non-COVID-19 vaccination reports, obesity was higher at 1.75 percent versus 0.67 percent, while hypertension was lower at 0.35 percent versus 1.43 percent. Compared with Bell’s palsy reports, hypertension was again lower, 0.35 percent versus 5.6 percent. Despite these statistically significant differences, absolute comorbidity prevalence remained low across all groups, generally below 10 percent and most commonly between 0 and 2 percent.

The authors conclude that no evidence of a modifying role for hypertension, diabetes, dyslipidemia, or obesity was observed for the increased reporting of myocarditis and pericarditis among young adult males following mRNA COVID-19 vaccination. They caution, however, that the higher prevalence of obesity and dyslipidemia seen in some internal comparisons may warrant further investigation.

Interpreting these findings requires careful attention to the limitations of spontaneous reporting systems. VAERS collects reports submitted by healthcare professionals, vaccine manufacturers, and the public, and functions as an early warning system rather than a definitive measure of causality or incidence. Causality between vaccination and myocarditis or pericarditis cannot be established from VAERS data alone, and some reports may reflect coincidental events or alternative causes, including prior viral infections. Three myocarditis reports documented a previous COVID-19 infection, which could have represented an alternative cause, though these cases were retained because they had been reported as suspected adverse events following vaccination. Comprehensive clinical adjudication of all reports was not feasible given the volume and structure of the database.

A more significant concern is under-ascertainment of comorbidities. While myocarditis and pericarditis are generally coded in structured symptom fields, comorbidities are often documented inconsistently within free-text history and narrative sections. The researchers used a keyword-based search algorithm across the HISTORY, CUR_ILL, and SYMPTOM_TEXT variables, with manual review of hypertension reports to distinguish pre-existing from incident cases. Internal comparisons showed similarly low comorbidity reporting across all comparator groups, suggesting that under-documentation was widespread rather than specific to myocarditis and pericarditis reports, and that the true prevalence of these conditions among affected individuals was likely underestimated. The healthy vaccine effect, in which individuals who seek vaccination may differ in health-seeking behavior and overall health status, may also contribute to lower observed comorbidity rates, though the authors argue this does not fully account for the markedly low prevalence in the reports.

Methodological challenges further complicate the analysis. None of the identified literature studies provided prevalence estimates specifically stratified for males aged 18 to 30, the study’s target population, limiting direct comparability between observed and expected groups. Some estimates came from selected populations such as veterans, healthcare workers, or regional healthcare systems, which may not represent the broader vaccinated population. VAERS also does not collect information on race or ethnicity, though the prevalence of these comorbidities is known to vary across subpopulations. The authors emphasize that the study was hypothesis-generating by design and call for formal hypothesis-testing studies using healthcare databases, potentially examining other comorbidities, history of viral infection, lifestyle and behavioral factors, race and ethnicity, allergies, and concomitant medication use. Despite the caveats, they argue that disproportionality and internal comparison approaches within spontaneous reporting databases can still offer valuable, timely insights in emergency public health settings such as mass vaccination campaigns, where identifying potential susceptibility factors matters most.

Subject of Research: Pre-existing cardiovascular comorbidities as potential risk modifiers for myocarditis and pericarditis following mRNA COVID-19 vaccination in young adult males, analyzed through VAERS disproportionality methods

Article Title: Pre–existing Comorbidities as Potential Risk Modifiers for New-Onset Myocarditis and Pericarditis following mRNA COVID-19 Vaccination in Males Aged 18–30 in the United States: A Disproportionality Analysis using VAERS Spontaneous Reporting Data

Article References: Salem, M. S., Moride, Y., & Bégaud, B. (2026). Pre–existing Comorbidities as Potential Risk Modifiers for New-Onset Myocarditis and Pericarditis following mRNA COVID-19 Vaccination in Males Aged 18–30 in the United States: A Disproportionality Analysis using VAERS Spontaneous Reporting Data. Drugs – Real World Outcomes, 13(3), 409-419. https://doi.org/10.1007/s40801-026-00568-4

Image Credits: AI Generated

DOI: 10.1007/s40801-026-00568-4

Keywords: myocarditis, pericarditis, mRNA COVID-19 vaccines, VAERS, disproportionality analysis, observed-versus-expected, hypertension, diabetes, dyslipidemia, obesity, young adult males, vaccine safety