Comparability of clinical trials and spontaneous reporting data regarding COVID-19 vaccine safety

Severe adverse events (AEs) after COVID-19 vaccination are not well studied in randomized controlled trials (RCTs) due to rarity and short follow-up. To monitor the safety of COVID-19 vaccines (Pfizer vaccine dose 1 and 2, Moderna vaccine dose 1 and 2, and Janssen vaccine single dose) in the U.S., especially regarding severe AEs, we compare the relative rankings of these vaccines using both RCT and the Vaccine Adverse Event Reporting System (VAERS) data. The risks of local and systemic AEs were assessed from the three pivotal COVID-19 vaccine trials and also calculated in the VAERS cohort consisting of 559,717 reports between December 14, 2020 and September 17, 2021. AE rankings of the five vaccine groups calculated separately by RCT and VAERS were consistent, especially for systemic AEs. For severe AEs reported in VAERS, the reported risks of thrombosis and GBS after Janssen vaccine were highest. The reported risk of shingles after the first dose of Moderna vaccine was highest, followed by the second dose of the Moderna vaccine. The reported risk of myocarditis was higher after the second dose of Pfizer and Moderna vaccines. The reported risk of anaphylaxis was higher after the first dose of Pfizer vaccine. Limitations of this study are the inherent biases of the spontaneous reporting system data, and only including three pivotal RCTs and no comparison with other active vaccine safety surveillance systems.

Automated summary

Limited studies have been conducted on severe adverse events (AEs) after COVID-19 vaccination due to their rarity and short follow-up. To monitor the safety of COVID-19 vaccines in the U.S., a study compared the rankings of different vaccines using both randomized controlled trials (RCTs) and the Vaccine Adverse Event Reporting System (VAERS) data, and assessed the risks of local and systemic AEs. Consistent rankings were observed between RCT and VAERS, particularly for systemic AEs.