The benefit-risk of the mRNA-1273 COVID-19 vaccine

By Tarun Sai LomteReviewed by Danielle Ellis, B.Sc.Dec 12 2022

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

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Background

The mRNA-1273 vaccine was approved for emergency use in the United States (US) and received a license recently in January 2022. Real-world evidence of mRNA vaccines from before the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron period indicates that vaccines effectively prevent COVID-19 cases, associated hospitalization, and death.

Nevertheless, cases of pericarditis and myocarditis associated with COVID-19 mRNA vaccination have been documented in the US, particularly among young adult males and adolescents. The US Food and Drug Administration (FDA) previously assessed the benefit-risk of the Comirnaty vaccine in people aged 16 or older.

The study and findings

In the present study, researchers performed the benefit-risk assessment of the mRNA-1273 vaccine in individuals aged 18 or above. They evaluated the benefits and risks per million individuals stratified by age, given the age-dependent risk of pericarditis and myocarditis after vaccination. The benefit endpoints were COVID-19 cases, hospitalizations, and admissions to an intensive care unit (ICU) preventable by vaccination.

The risk endpoints were vaccine-attributable cases of pericarditis/myocarditis, hospitalizations, ICU admissions, and death. The team determined vaccine-elicited protection over five months after completing the two-dose regimen (primary series). The incidence rates of COVID-19 cases and hospitalizations were assumed to be constant throughout this period.

The model predicted benefit-risk estimates for six scenarios, with the first scenario being the basal one. Scenarios 1, 2, and 3 represented the uncertainty in COVID-19 case incidence. Scenarios 1 and 4 represented VE uncertainty against emergent SARS-CoV-2 variants. Scenarios 1, 5, and 6 represented the uncertainty in the pericarditis/myocarditis rates attributable to vaccination.

The authors assumed SARS-CoV-2 Omicron as the dominant variant for five scenarios (1, 2, 3, 5, and 6) and 30% and 72% vaccine effectiveness (VE) against COVID-19 cases and hospitalization, respectively. For scenario 4, SARS-CoV-2 Delta was assumed as the predominant variant, and the VE was 80% and 90% against COVID-19 cases and hospitalizations.

VE against death was equal to that against hospitalization for all scenarios. Age-stratified incidences of pericarditis/myocarditis were calculated for the second vaccine dose and used as input for the risk of double-vaccinated individuals. The risk after the first vaccination was not considered, given that most myocarditis cases have been reported after the second vaccination.

For scenarios 1, 2, 3, and 4, the authors used the rate of pericarditis/myocarditis cases predicted by a prior meta-analysis, whereas for scenarios 5 and 6, 2.5^th and 97.5^th percentiles were used, respectively. The present analysis was limited to males aged 18 to 64 because data on females of all ages and males >65 were rare.

The model predicted that vaccinating a million males aged 18 to 25 with two mRNA-1273 doses would have prevented 82,484 COVID-19 cases, 4,766 associated hospitalizations, 1,144 ICU admissions, and 51 deaths in the base scenario. Nonetheless, this would have resulted in 128 cases of myocarditis/pericarditis, with 110 hospitalizations and zero ICU admissions/deaths.

These observations provided the benefit-risk of groups with the highest potential risk of pericarditis/myocarditis during the SARS-CoV-2 Omicron-dominated period and explicitly indicated the benefits of vaccination over risks. The results of five additional scenarios also suggested that COVID-19 vaccination outweighed the associated risks.

Conclusions

The findings suggest that the benefits of Moderna’s COVID-19 vaccine (mRNA-1273) outweigh the risks among males aged 18 to 64 across all scenarios. Further, given the evidence of a lower risk of myocarditis in females and older males (> 65 years) after COVID-19 vaccination, it can be anticipated that the benefit-risk profile of the mRNA-1273 vaccine would be more favorable in these populations compared to the male population.

Notably, given the uncertainty in the pandemic trajectory, the assumption of a constant rate of COVID-19 incidence would have created a high uncertainty on benefit outcomes. The estimated benefits of COVID-19 vaccination will decline if the VE decreases against emergent SARS-CoV-2 variants.

If the vaccine-elicited protection decays differentially against infection and severe disease within five months after the second dose, it may attenuate the benefits of vaccination. In addition, females and people older than 65 years of either sex were not considered in the current investigation due to the rarity of pericarditis/myocarditis cases in these demographic groups.

The authors also did not assess specific demographic groups, such as comorbid individuals for whom data are limited. Importantly, these findings helped inform the US FDA’s licensure decision on Moderna’s vaccine, and the purpose of this publication was to increase transparency and communicate that the benefits of Moderna outweighed its risks.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources