In an interim analysis of surveillance data from 6.2 million persons who received 11.8 million doses of an mRNA vaccine, event rates for 23 serious health outcomes were not significantly higher for individuals 1 to 21 days after vaccination compared with similar individuals at 22 to 42 days after vaccination, according to a study published in JAMA by Corresponding author, Nicola P. Klein, MD, PhD, Kaiser Permanente Vaccine Study Center.
This analysis found no significant associations between vaccination with mRNA COVID-19 vaccines and selected serious health outcomes 1 to 21 days after vaccination, although CIs were wide for some rate ratio estimates and additional follow-up is ongoing.
Safe and effective vaccines against SARS-CoV-2 are critical to ending the pandemic. Two messenger RNA (mRNA) vaccines (BNT162b2, Pfizer-BioNTech; and mRNA-1273, Moderna) were the first SARS-CoV-2 vaccines authorized in the US. Large phase 3 trials for BNT162b2 and mRNA-1273 demonstrated that both vaccines were more than 94% effective against symptomatic SARS-CoV-2 infection. Neither trial reported serious safety findings, and both observed low incidence of serious adverse events.
When the first COVID-19 vaccine was administered in December 2020, weekly monitoring started immediately. This report includes interim findings on risk of adverse events after receipt of mRNA COVID-19 vaccines through June 2021.
In this interim analysis of surveillance monitoring of more than 11.8 million doses of 2 mRNA vaccines in a diverse population and weekly analyses from December 14, 2020, to June 26, 2021, no vaccine-outcome association met the prespecified threshold for a signal. Incidence of selected serious outcomes was not significantly higher 1 to 21 days postvaccination compared with 22 to 42 days postvaccination for any of the outcomes. For the less frequent outcomes, CIs were wide and did not necessarily exclude clinically relevant increases associated with vaccination, and surveillance is ongoing.
In response to concerns regarding an association between thromboembolic outcomes with thrombocytopenia and ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV.2.S (Janssen) vaccines, surveillance for additional outcomes (cerebral venous sinus thrombosis and thrombosis with thrombocytopenia syndrome) was initiated. There has been no evidence that these outcomes are associated with mRNA vaccines. Close monitoring will continue for thromboembolic outcomes with thrombocytopenia after vaccination with all COVID-19 vaccines, including the Ad26.COV.2.S vaccine.
Analyses of all ages combined did not detect a significant association between myocarditis/pericarditis and mRNA vaccines. However, consistent with case reports, supplemental analyses of confirmed cases among individuals aged 12 to 39 years yielded an elevated RR estimate. Significant clustering within the first week after vaccination, especially after dose 2, provides additional evidence of an association between mRNA vaccines and myocarditis/pericarditis in younger individuals.
Anaphylaxis after COVID-19 mRNA vaccination has been observed more commonly than the estimated 1 to 2 cases per million doses reported after receipt of influenza vaccine and some other vaccines. Estimated anaphylaxis incidence rates after receipt of both BNT162b2 and mRNA-1273 vaccines in this study were similar to rates after receipt of mRNA vaccines in other reports, although somewhat higher than VAERS estimated reporting rates.
In contrast, estimated anaphylaxis incidence rates were much lower than the 24.7 cases of confirmed anaphylaxis per 100 000 vaccinees estimated through prospective surveillance of healthcare workers. Consistent with reports from the European Union and Japan, nearly all anaphylaxis after receipt of mRNA vaccines occurred among female recipients. Although the biological mechanism for the higher incidence among female vaccinees is not clear, it may be related to genes, hormones, and environmental and immunologic factors.
The phase 3 trials for both the BNT162b2 and mRNA-1273 vaccines noted that the incidence of Bell palsy was higher in the vaccine group than in the placebo group. Among nearly 40,000 vaccinees in both trials combined, there were 7 cases of Bell palsy vs 1 in the placebo group. In this current surveillance, neither the primary analyses nor those with unvaccinated comparators found evidence of an association between Bell palsy and mRNA vaccines, a finding that is consistent with a recent analysis of cases reported to the World Health Organization database.