The continued emergence of SARS-CoV-2 variants and breakthrough infections following vaccination underscore the need to study the effectiveness of current COVID-19 vaccines in the real world.

To date, only two mRNA COVID-19 vaccines have been approved for marketing, mRNA-1273 developed by Moderna and BNT162b2 developed by Pfizer/BioNTech, which have proven to be very effective in preventing severe illness, hospitalization and death due to SARS-CoV-2 infections.

However, the two mRNA vaccines induced different humoral immune responses, with data showing that humoral antibody responses were significantly higher with two doses of mRNA-1273 vaccine than with two doses of BNT162b2 vaccine. The higher humoral antibody response implies greater protection against SARS-CoV-2. In addition, there are data showing that breakthrough infections were higher after two doses of BNT162b2 vaccine than after two doses of mRNA-1273 vaccine during the Delta epidemic. These suggest to us that the two mRNA vaccines may have different effects in the real world.

On May 2, 2022, researchers at Optum Labs, a scientific healthcare organization, published a research paper in Nature Communications titled: Comparative effectiveness over time of the mRNA-1273 (Moderna) vaccine and the BNT162b2 (Pfizer-BioNTech) vaccine.

This retrospective cohort study of nearly 4 million individuals in the United States who received two doses of mRNA-1273 or BNT162b2 vaccine investigated the relationship between their severity of infection and the timing of vaccination to understand the actual performance and comparative effectiveness of these two mRNA vaccines. The primary outcome of this study was the rate of SARS-CoV-2 infections on days 30, 60, and 90 after the second dose of mRNA-1273 vaccine or BNT162b2 vaccination.

Of the nearly 4 million individuals who received two doses of mRNA-1273 vaccine (40%) or BNT162b2 vaccine (60%), a total of 8,848 were documented to be infected with SARS-CoV-2, of which 3,090 (35%) had previously received mRNA-1273 vaccine and 5,758 (65%) had previously received BNT162b2 vaccine.

Statistical results showed significant differences in infections over time between mRNA-1273 vaccination and BNT162b vaccination, with a lower probability of acquiring COVID-19 over time after mRNA-1273 vaccination. However, there was no statistically significant difference between the two mRNA vaccines over time for hospitalization, admission to the ICU, death, or transfer to hospice care.

This large retrospective analysis shows that there is a significant difference in the prevention of SARS-CoV-2 infections after mRNA-1273 vaccination and BNT162b vaccination, and that this difference is widening over time. The data show that for every 1 million people who received two doses of mRNA vaccine, there were 3,448 more breakthrough infections in people who received BNT162b vaccine than those who received mRNA-1273 vaccine at day 90.

Overall, mRNA-1273 vaccination was slightly more effective than BNT162b vaccination in preventing infection after complete vaccination. However, both vaccines were comparable in terms of protection against serious illness (hospitalization, ICU, or death) within 90 days of complete vaccination.