Lower risk of vaccine-breakthrough infections for mRNA-1273 recipients


Recently, a team of researchers examined breakthrough infections, hospitalizations, and mortality rates in double-dose messenger RNA (mRNA) vaccine recipients in a research letter published in the Journal of American Medical Association (JAMA).

Vaccine-induced immune responses against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) wane after six months of administration of the mRNA vaccines – BNT162b2 (Pfizer) and mRNA-1273 (Moderna). Several reports of vaccine-breakthrough infections have emerged, which is another cause for concern.

The latest surge in coronavirus disease 2019 (COVID-19) cases across many countries due to the new, highly mutated SARS-CoV-2 Omicron variant has been alarming. As a result, several nations have approved the administration of booster doses of the COVID-19 vaccines to control the number of infections.

Research Letter: Comparison of mRNA-1273 and BNT162b2 Vaccines on Breakthrough SARS-CoV-2 Infections, Hospitalizations, and Death During the Delta-Predominant Period. Image Credit: Carl DMaster/Shutterstock

The study

The present study collected deidentified electronic health records (EHRs) of COVID-19 patients showing diverse geography, race, ethnicity, and income.

TriNetX analytics, a cloud-based platform, was used to access and analyze patient-level data. Individuals who received two doses of BNT162b2 and mRNA-1273 vaccines between December 2020 and November 2021 and had a positive test for SARS-CoV-2 RNA after 14 days of second vaccination between July 2021 and November 2021 were included to study breakthrough infections.

Further, these individuals had no prior history of SARS-CoV-2 infection and have not received a booster shot of the SARS-CoV-2 vaccine.

Propensity scores were matched for the two cohorts – mRNA-1273 and BNT162b2 groups – for demographics, social determinants of health, transplants, COVID-19-related comorbidities, and Kaplan-Meier survival and Cox proportional hazard analyses were performed. Breakthrough infection cases per 1,000 person-days (monthly incidence rates) were compared between the two groups.


A total of about 62,628 and 574,538 fully vaccinated individuals received mRNA-1273 and BNT162b2 vaccines, which included around 3078 and 18,737 breakthrough infections, respectively. The authors noted that the mRNA-1273 cohort comprised older people and had more COVID-19-related comorbidities relative to the BNT162b2 coho. However, propensity score matching decreased these differences. An increase in the monthly incidence rate of breakthrough infections was observed in both cohorts from July 2021 to November 2021, but it was comparatively higher for the BNT162b2 cohort than the mRNA-1273 cohort.

Hospitalization and mortality rate in infected patients for 60 days after a positive test were analyzed and compared between the two cohorts. The hospitalization risk was found to be 12.7% for mRNA-1273 vaccinees and 13.3% for BNT162b2 vaccine recipients. The mortality rate was 1.14% and 1.1% for mRNA-1273 and BNT162b2 recipients, respectively. After propensity-score matching of the two cohorts, the authors observed a lower risk of hospitalization for those who received two doses of Moderna vaccine when compared to people fully vaccinated with the BNT162b2 vaccine. The mortality rate showed no significant differences between the two cohorts after matching.


The present study, which was conducted when the SARS-CoV-2 Delta variant was the dominant strain, noted that breakthrough infections among people who received the mRNA-1273 vaccine were less frequent when compared to the BNT162b2 vaccine recipients. Similarly, a lower risk of hospitalization was observed for infected individuals who received the Moderna vaccine. The hazard ratios were also significantly lower for the matched mRNA-1273 cohort compared with the matched BNT162b2 cohort.

Although the study observed significant differences between the two cohorts, it is limited by a few factors that include the observational and retrospective nature of the study, which could introduce selection and follow-up biases.

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