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Multiorgan Outcomes Following BNT162b2 mRNA Vaccination vs SARS-CoV-2 Infection: A 30-Million-Person Real-World
Eman A Toraih1,2, Dara Bruce3, Mohammad H Hussein4
1Department of Cardiovascular Perfusion, SUNY Upstate Medical University, Syracuse, New York, 13210, USA. toraihe@upstate.edu.
NPJ Vaccines
|July 19, 2026
Summary
SARS-CoV-2 infection significantly increases cardiovascular risks, including myocarditis and mortality, especially in males. BNT162b2 vaccination substantially reduces these risks, offering a favorable cardiovascular risk-benefit profile.
Area of Science:
- Cardiology
- Infectious Diseases
- Vaccinology
Background:
- Limited comparative data exists on cardiovascular risks between SARS-CoV-2 infection and BNT162b2 vaccination across sexes.
- Understanding these distinct risk profiles is crucial for public health strategies.
Purpose of the Study:
- To directly compare cardiovascular, cerebrovascular, and mortality outcomes between SARS-CoV-2 infection and BNT162b2 vaccination.
- To evaluate these risks across different immunological exposure groups and biological sexes.
Main Methods:
- A large-scale retrospective cohort study of 30.3 million individuals using the TriNetX Research Network (December 2020-December 2024).
- Stratification into four cohorts: uninfected/unvaccinated, infected/unvaccinated, vaccinated-only, and hybrid immunity.
- Analysis of 50 prespecified outcomes across four temporal windows, stratified by sex.
Main Results:
- SARS-CoV-2 infection showed 3- to 5-fold increases in cardiovascular events (e.g., myocarditis, all-cause mortality), with persistent risks beyond nine months.
- BNT162b2 vaccination reduced major adverse cardiovascular events (MACE) by 65-76% (0-3 months).
- Hybrid immunity offered additional MACE reduction; males showed late pericarditis elevation. Two vaccine doses maximally reduced mortality and myocarditis.
Conclusions:
- SARS-CoV-2 infection poses substantially greater and more sustained cardiovascular risk than BNT162b2 vaccination.
- BNT162b2 vaccination demonstrates a favorable cardiovascular risk-benefit profile compared to infection.
- Vaccination, particularly a completed primary series, is associated with significant reductions in adverse cardiovascular outcomes and mortality.
