Mounting safety data for SARS-CoV-2 mRNA vaccines

Reviewed by Erica Stohs, MD, MPH, University of Nebraska Medical Center and James “Brad” Cutrell, MD, UT Southwestern Medical Center

Two active surveillance programs analyzing adverse events following millions of administered mRNA vaccinations against SARS CoV-2 infection support their safety while one also suggests that risk of certain adverse events is more likely with SARS CoV-2 infection than vaccination.

In the New England Journal of Medicine, Barda and colleagues examined data from Israel’s largest health care organization to compare potential adverse events (AEs) within 6 weeks of receipt of BNT162b2 (Pfizer) vaccination. They compared AEs between vaccinated vs unvaccinated groups matched across a host of sociodemographic and clinical variables. They took the analysis one step further by comparing risk ratios for AEs between vaccinated vs unvaccinated and SARS-CoV2 infected vs uninfected individuals. Myocarditis, lymphadenopathy, appendicitis, and herpes zoster infection had statistically significant risk ratios for vaccinated vs unvaccinated persons. Specifically, the RR for myocarditis was 3.24 (risk difference of 2.7 events per 100,000 persons). However, the risk of myocarditis following infection was much higher, with a RR for myocarditis in SARS-CoV-2 infected vs uninfected of 18.3 (risk difference of 11 events per 100,000 persons). Other serious AEs that were significantly elevated following SARS-CoV-2 infection included acute kidney injury, thromboembolic events, myocardial infarction, and arrhythmias.

In JAMA, Klein and colleagues analyzed surveillance data from over 6 million people in the US receiving nearly 12 million doses of mRNA vaccine to compare serious health outcomes occurring in the first 3 weeks of vaccination (when AEs are most likely) vs 4-6 weeks following vaccination. Data came from one of the largest health care plans in 8 geographically diverse sites in the US, comprising 3.6% of the US population. They calculated incidences and rate ratios for 23 serious AEs including anaphylaxis, myocarditis, venous thromboembolic events, appendicitis, and certain serious neurologic sequelae. They detected no signal for vaccine-outcome associations. Supplemental analyses did compare AEs in vaccinated vs unvaccinated groups; the risk ratio of 1.39 for myocarditis/pericarditis was statistically significant. The incidences for anaphylaxis were 4.8 per million doses of Pfizer and 5.1 per million of Moderna vaccine.

While large randomized controlled trials of SARS-CoV-2 vaccines gaining FDA approval were performed in largely healthy participants, active surveillance programs continue to amass data from millions receiving vaccination in real-world settings. These studies continue to better define the safety profile of these vaccines and support continued vaccination efforts.

Barda N, et al. Safety of the BNT162b2 mRNA COVID-19 vaccine in a nationwide setting. NEJM 2021;385:1078-90. DOI: 10.1056/NEJMoa2110475.

We use cookies to help improve your experience