In a recent study posted to medRxiv*, researchers evaluated adverse events (AEs) in older adults after messenger ribonucleic acid (mRNA) vaccination for coronavirus disease 2019 (COVID-19).

*Study: Evaluation of Potential Adverse Events Following COVID-19 mRNA Vaccination Among Adults Aged 65 Years and Older: A Self-Controlled Study in the U.S.. Image Credit: myboys.me/Shutterstock*

Background

The United States (US) Food and Drug Administration (FDA) approved COVID-19 vaccines under emergency use authorization for primary and booster vaccination. These included Pfizer’s BNT162b2 and Moderna’s mRNA-1273 for individuals aged six months or older and Novavax for those aged 12 or above. Rapid cycle analysis (RCA) is a near real-time surveillance method to screen for elevated risks of AEs post-vaccination.

This method revealed a significant association between primary vaccination with BNT162b2 and pulmonary embolism (PE), acute myocardial infarction (AMI), immune thrombocytopenia (ITP), and disseminated intravascular coagulation (DIC). Another study reported associations of BNT162b2 and mRNA-1273 booster vaccination with Bell’s Palsy and myocarditis/pericarditis (Myo/Peri), respectively. These AEs may not represent true safety concerns as RCA fails to establish vaccines as causality.

About the study

The present study summarized findings from two independent studies on COVID-19 vaccine safety. In particular, they examined the risks of PE, AMI, ITP, and DIC after primary mRNA vaccination and the risk of ITP, AMI, BP, Myo/Peri, and PE post-booster mRNA vaccination. They defined the first two doses of the COVID-19 mRNA vaccine (mRNA-1273 or BNT162b2) as the primary series and the subsequent third dose as the booster.

The incidence rates of AEs due to vaccination within the hypothesized risk interval were compared to those during a control interval for primary and booster vaccinations among adults aged 65 or older. Both studies (primary and booster series) included Medicare Fee-for-Service beneficiaries vaccinated with at least one dose and who experienced an incident AE during the follow-up.

The primary series study analyzed the post-vaccination risk of DIC, AMI, and PE within a risk window of 28 days and ITP in a 42-day risk window. The booster study evaluated the risk of PE and AMI using a 28-day risk window, Myo/Peri using a 21-day risk window, and ITP and BP within a risk window of 42 days.

Subjects were followed up until the end of the observation/study, fourth vaccination, or death. Medical records were reviewed for cases from the two studies classified as true, indeterminate, or non-cases. A conditional Poisson regression method was applied to compute the incidence rate ratio comparing rates for each AE in the risk and control intervals.

Findings

More than 3.3 million individuals completed the primary series, and 6.1 million were boosted with either mRNA vaccine. Case counts for AMI were 3,653 (primary series) and 16,042 (booster), in-patient PE were 2,470 (primary) and 5,085 (booster), DIC were 254 (primary only), BP were 3,268 (booster-only), ITP were 1,085 (primary) and 88 (booster), and Myo/Peri were 1,295 (booster-only).

BNT162b2 recipients were younger, more likely to live in a nursing home, and less likely to live in a rural area than mRNA-1273 recipients in both studies. In the primary series study, DIC and AMI exhibited a high case fatality rate of 67% and 34%. The risk of AMI was significantly increased following primary vaccination with BNT162b2.

Nonetheless, this effect was insignificant after adjusting for seasonality or outcome misclassification and excluding individuals with prior COVID-19. The risk of AMI post-BNT162b2 booster was not elevated. The risk of AMI was not significantly elevated after primary or booster mRNA-1273 vaccination.

The risk of inpatient PE increased significantly after primary BNT162b2 vaccination, which remained significant in the adjusted analysis. By contrast, it was significantly reduced following the BNT162b2 booster vaccination. The primary series study revealed no significant increase in the risk of inpatient PE post-vaccination with mRNA-1273, while the risk was significantly reduced after mRNA-1273 booster vaccination.

BP risk increased significantly after booster vaccination with the BNT162b2 vaccine but not with mRNA-1273 and was consistent in adjusted analyses. ITP risk did not increase after primary/booster vaccination with either mRNA vaccine. Similarly, the risk of DIC was not elevated following vaccination. Myo/Peri risk was not significantly increased for either vaccine.

Conclusion

In summary, the researchers found no significant increases in the risks of DIC, Myo/Peri, AMI, and ITP following COVID-19 mRNA vaccination in the elderly US population. The results were inconsistent for PE. The risk of BP was slightly increased after mRNA vaccination. Overall, these findings corroborate the safety of mRNA vaccines against COVID-19 and are in line with the conclusion that vaccination benefits outweigh the risks.

*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.