An Israel study estimates vaccinated persons' risk of side effects including myocarditis, relative to the risk brought on by SARS-CoV-2 infection.
A nationwide assessment of Israel in the 5 months during initiated COVID-19 vaccine administration showed Pfizer-BioNTech vaccine BNT162b2 (Comirnaty) was not associated with increased risk of most adverse events relative to the risk of such events due to SARS-CoV-2 infection.
The data from 2.4 million vaccinated people showed, for example, that risk of myocarditis was nearly 6-fold greater in those who had been infected by SARS-CoV-2 than in those who received the mRNA vaccine.
The new findings were published in The New England Journal of Medicine this week.
Israel was noted for its expedited and comprehensive vaccine rollout strategies following the authorization of Pfizer-BioNTech’s and Moderna’s products in late December. The small country had fully vaccinated more than half its population against COVID-19 by late March this year, but has since plateaued to approximately 60% full vaccination rate as of today.
Led by Noam Barda, MD, of the Clalit Research Institute in Tel Aviv, investigators sought to interpret the safety of the widely distributed Pfizer-BioNTech 2-dose vaccine. They noted that pivotal phase 3 trials for COVID-19 vaccines have identified potential adverse events including lymphadenopathy, Bell’s palsy—and more exclusively to BNT162b2, appendicitis, hypersensitivity reactions, acute myocardial infarction (MI), and cerebrovascular accidents.
“However, phase 3 trials may have inherent limitations in assessing vaccine safety because of a small number of participants and a healthier-than-average sample population,” Barda and colleagues wrote. “Hence, they are often underpowered to identify less common adverse events.”
The investigators used observational data from the Clalit Health Services, the largest of Israel’s 4 integrated payer-provider health care organizations that are required to provide health care coverage and the insurer for 52% of the country’s population. They individually matched vaccinated persons to unvaccinated persons, based on sociodemographic and clinical factors, among the population to have experienced identified adverse events (n = 884,828).
Patients had no previous diagnosis of the adverse event. Risk ratios and differences at 42 days post-vaccination were defined via Kaplan-Meier. A similar analysis was conducted with patients infected with SARS-CoV-2, matched to those uninfected by the virus.
Investigators observed an associated elevated risk of myocarditis among people vaccinated with BNT162b2 (risk ratio [RR], 3.24; 95% CI, 1.0 – 4.6), as well as increased risk of lymphadenopathy (RR, 2.43; 95% CI, 2.05 – 2.78), appendicitis (RR, 1.40; 95% CI, 1.02 – 2.01), and herpes zoster infection (RR, 1.43; 95% CI, 1.20 -1.73).
For each of the 4 adverse events, the risk difference per 100,000 vaccinated persons were:
Bell’s palsy (RR, 1.32; 95% CI, 0.92 – 1.86), myocardial infarction (RR, 1.07; 95% CI, 0.74 – 1.60), and pericarditis (RR, 1.27; 95% CI, 0.68 – 1.24) were among the adverse events associated with slightly increased risk among vaccinated persons.
However, SARS-CoV-2 infection was associated with a significantly greater risk of myocarditis (RR, 18.28; 95% CI, 3.95 – 25.12; risk difference, 11.0 per 100,000; 95% CI, 5.6 – 15.8). It additionally was associated with significantly increased risk of pericarditis; arrhythmia; deep vein thrombosis; pulmonary embolism; myocardial infarction; intracranial hemorrhage; and thrombocytopenia.
Infection was not estimated to have significant impact on incidence of lymphadenopathy, appendicitis, or herpes zoster infection.
Barda and colleagues noted some “initially unexpected effects” observed in the assessment, including the seemingly protective nature of BNT162b2 versus conditions including anemia and intracranial hemorrhage—events identified as complications brought on by SARS-CoV-2 infection.
Overall, their findings indicated an estimated increase incidence of a few adverse events in the 42 days following BNT162b2 vaccination—most being mild in nature, some such as myocarditis being more severe.
“However, our results indicate that SARS-CoV-2 infection is itself a very strong risk factor for myocarditis, and it also substantially increases the risk of multiple other serious adverse events,” they concluded. “These findings help to shed light on the short- and medium-term risks of the vaccine and place them in clinical context.”
Future studies are necessary to estimate potential long-term adverse events associated with COVID-19 vaccines, they wrote.