Benefits and risks of the mRNA-1273 COVID-19 vaccine

In a recent study posted on medrex sib*Preprint server, researchers modeled the benefit-risk of Moderna’s coronavirus disease 2019 (COVID-19) mRNA-1273 vaccine.

Background

The mRNA-1273 vaccine was approved for emergency use in the United States (US) and was recently licensed in January 2022. The real-world period of evidence for mRNA vaccines prior to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron suggests that vaccines effectively prevent COVID-19 cases, associated hospitalizations, and deaths. is showing.

Nonetheless, cases of pericarditis and myocarditis associated with COVID-19 mRNA vaccination have been reported in the United States, particularly among young adult men and adolescents. The U.S. Food and Drug Administration (FDA) previously evaluated the benefits and risks of his Comirnaty vaccine in people over the age of 16.

Research and Findings

In this study, researchers conducted a benefit-risk assessment of the mRNA-1273 vaccine in individuals aged 18 and older. They assessed benefits and risks per million people stratified by age, considering the age-dependent risk of post-vaccination pericarditis and myocarditis. Benefit endpoints were COVID-19 cases, hospitalizations, and intensive care unit (ICU) admissions preventable by vaccination.

Risk endpoints were cases of vaccine-induced pericarditis/myocarditis, hospitalization, admission to the ICU, and death. The team determined vaccine-induced protection over 5 months after completing two dosing regimens (primary series). The incidence of COVID-19 cases and hospitalizations was assumed to remain constant throughout this period.

The model predicted benefit and risk estimates for six scenarios, with the first scenario being the base scenario. Scenarios 1, 2, and 3 represent uncertainties in the case incidence of COVID-19. Scenarios 1 and 4 represent VE uncertainty for emerging SARS-CoV-2 variants. Scenarios 1, 5, and 6 represent uncertainties in the incidence of pericarditis/myocarditis resulting from vaccination.

The authors found that SARS-CoV-2 Omicron was the predominant variant in five scenarios (1, 2, 3, 5, and 6) with vaccine efficacy (VE) of 30 for COVID-19 cases and hospitalizations, respectively. I assumed it was % and 72%. In Scenario 4, SARS-CoV-2 Delta was assumed to be the predominant variant and VE was 80% and 90% for COVID-19 cases and hospitalizations.

VE for death was comparable to that for hospitalization in all scenarios. The age-stratified incidence of pericarditis/myocarditis was calculated for the second vaccination and used as an input for the risk of double-vaccinated individuals. Since most cases of myocardial inflammation were reported after her second vaccination, risks after the first vaccination were not considered.

For scenarios 1, 2, 3 and 4, the authors used the proportion of pericarditis/myocarditis cases predicted by previous meta-analyses, whereas for scenarios 5 and 6 it was 2.5^th and 97.5^th Percentiles were used for each. The current analysis was limited to men aged 18 to her 64, as data on women of all ages and men aged 65 and over were rare.

In this model, 2 doses of mRNA-1273 in 1 million men aged 18-25 years would result in 82,484 COVID-19 cases, 4,766 associated hospitalizations, 1,144 ICU admissions, and predicted that 51 deaths could be prevented. Nonetheless, this would have resulted in his 128 cases of myocarditis/pericarditis, 110 hospitalizations, and 0 ICU admissions/deaths.

These observations provide benefits and risks for groups at highest potential risk of pericarditis/myocarditis during periods of SARS-CoV-2 Omicron dominance and clarify the benefit of vaccination against risk. showed. Results from five additional scenarios also suggest that COVID-19 vaccination outweighs the associated risks.

Conclusion

The findings suggest that the benefits of Moderna’s COVID-19 vaccine (mRNA-1273) outweigh the risks for men aged 18 to 64 in all scenarios. Furthermore, given evidence of a lower risk of myocarditis in women and older men (>65 years) after COVID-19 vaccination, the benefit/risk profile of mRNA-1273 vaccine is more favorable in these populations. You can expect there to be. compared to the male population.

In particular, given the uncertainty in the trajectory of the pandemic, assuming a constant incidence of COVID-19, there would have been great uncertainty in the benefit outcome. , decreases as VE decreases for emerging SARS-CoV-2 variants.

If the vaccine-induced protection decays differently against infection and severe disease within 5 months after the second dose, the benefits of vaccination may be diminished. In addition, women and people aged 65 years and older of both genders were not considered in the current study because of the rarity of pericarditis/myocarditis cases in these demographic groups.

The authors also did not evaluate specific demographic groups, such as individuals with comorbidities for which data are limited. Importantly, these findings helped inform the US FDA’s licensing decision for Moderna’s vaccine. The purpose of this publication was to increase transparency and communicate that Moderna’s benefits outweigh its risks.

*Important Notices

medRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information. There is none