ABSTRACT
Vaccination with two injections of mRNA-1273 (100-μg) was shown to be safe and efficacious at preventing coronavirus disease 2019 (COVID-19) in the Coronavirus Efficacy (COVE) trial at completion of the blinded part of the study. We present the final report of the longer-term safety and efficacy data of the primary vaccination series plus a 50-μg booster dose administered in Fall 2021. The booster safety profile was consistent with that of the primary series. Incidences of COVID-19 and severe COVID-19 were higher during the Omicron BA.1 than Delta variant waves and boosting versus non-boosting was associated with significant reductions for both. In an exploratory Cox regression model adjusted for time-varying covariates, a longer interval between primary vaccination and boosting was associated with a significantly lower incidence of COVID-19 during the Omicron BA.1 wave. Boosting elicited greater immune responses against ancestral SARS-CoV-2 than the primary series, irrespective of prior SARS-CoV-2 infection. ClinicalTrials.gov: NCT04470427
Subject(s)
COVID-19ABSTRACT
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.
Subject(s)
COVID-19 , Myocarditis , PericarditisABSTRACT
Background: Growing evidence indicates a causal relationship between SARS-CoV-2 infection and myocarditis. Post-authorization safety data have also identified myocarditis as a rare safety event following mRNA COVID-19 vaccination, most notably among younger adult males and after dose 2. To further evaluate the potential risk after vaccination, we queried the Moderna global safety database to assess the occurrence of myocarditis/myopericarditis among mRNA-1273 vaccine recipients worldwide since first international Emergency Use Authorization issuance. Methods: Reports of myocarditis/myopericarditis entered into the Moderna global safety database from December 18, 2020 to September 30, 2021 were reviewed and classified based on the Brighton Collaboration case definition. The cumulative observed occurrence of myocarditis/myopericarditis was assessed by calculating the reported rate after any known dose of mRNA-1273 according to age and sex. This reporting rate was compared to a population-based incidence rate (US military) to calculate observed-to-expected rate ratios (RR). Results: Through September 30, 2021, a total of 1,439 cases of myocarditis/myopericarditis among approximately 151.1 million mRNA-1273 vaccine recipients were reported to the Moderna global safety database. The overall reporting rate among all vaccine recipients was 0.95 cases per 100,000 vaccine recipients, which was lower than the expected rate from the reference population (2.12 cases per 100,000 vaccine recipients; RR [95% CI]: 0.45 [0.42-0.48]). When stratified by sex and age, observed rates were highest for males aged [≤]39 years, particularly those aged 18-24 years (7.40 cases per 100,000 vaccine recipients), which was higher than expected (RR [95% CI]: 3.49 [2.88-4.22]). For males and females aged <18 years, the rate ratio for myocarditis was 1.05 (95% CI, 0.52-2.13) and 0.21 (95% CI, 0.04-0.94), respectively. When considering only cases occurring within 7 days after vaccination, the observed rate was highest for males aged 18-24 years after dose 2 (4.9 cases per 100,000 doses administered). Conclusion: Myocarditis/myopericarditis accounted for 0.4% of adverse events reported to the Moderna global safety database after mRNA-1273 vaccination; rates were higher than expected in males aged 18-24 years, with most occurring by 7 days after dose 2, but were not higher than expected for the overall population of vaccine recipients and were lower than that observed in individuals infected with SARS-CoV-2.