Global Safety Assessment of Adverse Events of Special Interest Following 2 Years of Use and 772 Million Administered Doses of mRNA-1273 (preprint)

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.

Antibody Response Following COVID-19 Boosters During the Omicron Wave in the United States: A Decentralized, Digital Health, Real-World Study (preprint)

As the coronavirus disease 2019 (COVID-19) pandemic evolves, new methods that enable real-world studies can provide public health information regarding long-term immunity following vaccination and booster campaigns. We conducted an observational trial to assess antibody levels against SARs-CoV-2 following COVID-19 vaccine boosters in adults in the United States during the omicron wave. This study utilized mobile health technology to recruit and enroll participants in combination with at-home blood collection self-conducted by participants and self-administration of surveys. The results show that when compared with the Pfizer-only primary/booster COVID-19 vaccine, the Moderna-only primary/booster vaccine substantially boosts and maintains high antibody titers over time against the ancestral strain and variants, including BA.1; the geometric mean ratios were generally statistically significantly greater when comparing the Moderna-only to the Pfizer-only vaccine/booster series over much of the study period. These observations suggest that priming/boosting with the Moderna vaccine may be highly protective against COVID-19; such data are vital to inform future recommendations for COVID-19 boosters and to assess the emergence of variants.

Myocarditis After mRNA-1273 Vaccination: A Population-Based Analysis of 151 Million Vaccine Recipients Worldwide (preprint)

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.

Effect of COVID-19 on inequalities in premature mortality in England: an analysis of excess mortality by deprivation and ethnicity (preprint)

Objectives: To examine the impact of the COVID-19 pandemic on inequalities in premature mortality in England by deprivation and ethnicity. Design: A statistical model to estimate increased mortality in population sub-groups during the COVID-19 pandemic by comparing observed with expected mortality in each group based on trends over the previous five years. Setting: Information on deaths registered in England since 2015 was used, including age, sex, area of residence, and cause of death. Ethnicity was obtained from Hospital Episode Statistics (HES) records linked to death registration data. Participants: Population study of England, including all 569,824 deaths from all causes registered between 21 March 2020 and 26 February 2021. Main outcome measures: Excess mortality in each sub-group over and above the number expected based on trends in mortality in that group over the previous five years. Results: The gradient in excess mortality by deprivation was greater in the under 75s (most deprived had 1.25 times as many deaths as expected, least deprived 1.14) than in all ages (most deprived had 1.24 times as many deaths as expected, least deprived 1.20). Among the Black and Asian groups, all deprivation quintiles had significantly larger excesses than the most deprived White group and there were no clear gradients across quintiles. Among the White group, only the most deprived had more excess deaths than deaths directly involving COVID-19. Among the Black group all deprivation quintiles experienced more excess deaths than deaths directly involving COVID-19. Conclusion: The COVID-19 pandemic has widened inequalities in premature mortality by deprivation. Among those under 75, the direct and indirect effects of the pandemic on deaths have disproportionately impacted ethnic minority groups irrespective of deprivation, and the most deprived White group. Statistics limited to deaths directly involving COVID-19 understate the pandemic's impact on inequalities by deprivation and ethnic group at younger ages.

Factors indicating intention to vaccinate with a COVID-19 vaccine among older U.S. Adults (preprint)

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBACKGROUNDC_ST_ABSThe success of vaccination efforts to curb the COVID-19 pandemic will require broad public uptake of immunization and highlights the importance of understanding factors associated with willingness to receive a vaccine. METHODSAdults enrolled in the Heartline clinical study were invited to complete a COVID-19 vaccine assessment through the Heartline mobile application between November 6-20, 2020. Factors associated with willingness to receive a COVID-19 vaccine were evaluated using an ordered logistic regression as well as a Random Forest classification algorithm. RESULTSAmong 9,106 study participants, 81.3% (n=7402) responded and had available demographic data. The majority (91.3%) reported a willingness to be vaccinated. Factors most strongly associated with vaccine willingness were beliefs about the safety and efficacy of COVID-19 vaccines and vaccines in general. Women and Black or African American respondents reported lower willingness to vaccinate. Among those less willing to get vaccinated, 66.2% said that they would talk with their health provider before making a decision. During the study, positive results from the first COVID-19 vaccine outcome study were released; vaccine willingness increased after this report. CONCLUSIONSEven among older adults at high-risk for COVID-19 complications who are participating in a longitudinal clinical study, 1 in 11 reported lack of willingness to receive COVID-19 vaccine in November 2020. Variability in vaccine willingness by gender, race, education, and income suggests the potential for uneven vaccine uptake. Education by health providers directed toward assuaging concerns about vaccine safety and efficacy can help improve vaccine acceptance among those less willing. Clinicaltrials.gov NCT04276441