ABSTRACT
Background: The large-scale use of mRNA COVID-19 vaccines during the pandemic was associated with enhanced safety monitoring to ensure accurate and timely review of safety. We reviewed the mRNA-1273 (original strain) safety profile following 2 years of use (>772 million administered doses), primarily focusing upon predefined safety topics (ie, adverse events of special interest [AESI]) proposed in advance of COVID-19 vaccine use. Methods: Cumulative mRNA-1273 safety data from spontaneous adverse event (AE) cases reported to the Moderna, Inc., global safety database (GSDB) between December 18, 2020, and December 17, 2022, were included. Reporting rates of AESI were calculated per 1 million doses of mRNA-1273 administered. Observed-to-expected (OE) ratios were computed by comparing observed rates of AESI to the background/expected rate for these events to evaluate potential associations with mRNA-1273. Results: There were 658,767 identified case reports, associated with 2,517,669 AEs. Most AEs were non-serious (83.4%); 0.7% were fatal. AESI represented 13.7% of all AEs, with reporting rates for most AESI below the expected background incidence. Exceptions included anaphylaxis (OE ratio 3 days after vaccination, 2.19 [95% CI, 2.02-2.37]), myocarditis (OE ratio 7 days after vaccination, 1.41 [1.32-1.51]; among men aged 12-40 years, 9.75 [7.74-12.3]; and individuals aged 12-40 years, 3.51 [3.19-3.86]), and pericarditis (OE ratio 7 days after vaccination in individuals aged 12-40 years, 2.54 [2.16-2.99]). Conclusions: With the exceptions of anaphylaxis, myocarditis, and pericarditis, this safety analysis of mRNA-1273 did not find evidence to suggest an increased risk for AESI identified for enhanced monitoring ahead of COVID-19 vaccine use.