Efficacy of mRNA-1273 and BNT162b2 vaccines in Qatar

To the editor:

Increasing evidence suggests that coronavirus disease 2019 (Covid-19) vaccines differ in efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or severe Covid-19.^1-3 However, data from controlled studies, including direct comparisons of immunity induced by these vaccines, are lacking. A study was conducted to compare the protection of Qatar’s mRNA-1273 (Moderna) and BNT162b2 (Pfizer–BioNTech) vaccines.

Data from the National Covid-19 Electronic Health Database was used to emulate randomized controlled trials and documented outbreaks of SARS-CoV-2 infection after the first and second doses of mRNA-1273. We designed two matching retrospective cohort studies to assess rates. BNT162b2 vaccine. Both studies included the same population vaccinated with the mRNA-1273 or BNT162b2 vaccine between December 21, 2020 and October 20, 2021 (). Supplementary appendix, Available at NEJM.org with the full text of this letter). Persons were matched one-to-one according to the vaccination calendar week and other variables, and matching cohorts excluded those with confirmed SARS-CoV-2 infection prior to vaccination.

A total of 192,123 people who received the mRNA-1273 vaccine twice were consistent with the same number of people who received the BNT162b2 vaccine twice (Fig. S1, Table S3, and Section S5). Among those vaccinated with mRNA-1273, 878 breakthrough infections were recorded after the second dose with a median follow-up of 89 days. Three of these infections progressed to severe Covid-19 (acute hospitalization), but none progressed to serious illness (intensive care unit hospitalization) or death.

Figure 1. Figure 1. Breakthrough infection after the second dose of mRNA-1273 and BNT162b2 vaccines.

The cumulative incidence of breakthrough infections after the second dose in a matched cohort of mRNA-1273 vaccinated and BNT162b2 vaccinated has been shown. CI shows confidence intervals, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2.

Among those vaccinated with BNT162b2, a median follow-up of 86 days recorded 1262 breakthrough infections after the second dose. Of these infections, seven progressed to severe Covid-19, one progressed to serious illness, and one died. Both vaccination cohorts were prone to breakthrough infections among those who were long-term from the time of vaccination (Figure 1 And Table S5).

Differences between the two vaccine cohorts in documented infection incidence began 3 weeks after the first dose (Figure S2). The incidence of SARS-CoV-2 infection and severe Covid-19 was lower in mRNA-1273 vaccinated than in BNT162b2 vaccinated with a single dose (Section S5). At 6 months follow-up after the second dose, the estimated cumulative incidence of breakthrough infections was 0.59% (95% confidence interval). [CI], 0.55 to 0.64 among those who received the mRNA-1273 vaccine), 0.84% ​​(95% CI, 0.79 to 0.89) among those who received the BNT162b2 vaccine (95% CI, 0.79 to 0.89) (Figure 1). Approximately 90 days after the second dose, both incidence curves began to bend upwards during periods of low incidence of infection in Qatar.^2,4 This suggested a gradual decline in vaccine protection.^Four

The estimated overall adjusted hazard ratio for infection after the second dose of the mRNA-1273 vaccine compared to the second dose of the BNT162b2 vaccine was 0.69 (95% CI, 0.63 to 0.75). The adjusted hazard ratio was almost stable over time after the second dose at about this value (Figure 1). The estimated overall adjusted hazard ratio for Covid-19 after the second dose was 0.37 (95% CI, 0.10 to 1.41).

Vaccination with mRNA-1273 was associated with a lower incidence of SARS-CoV-2 breakthrough infections than vaccination with BNT162b2. This finding is consistent with the difference in neutralizing antibody titers.^Five However, both vaccines provided strong protection against Covid-19-related hospitalizations and deaths. Both vaccines also had a very similar pattern of defense accumulation, starting with the first dose and waning months after the second dose. The nature of vaccine immunity, which is built after vaccination and weakens over time, appeared to be similar in both vaccines.

Dr. Rice J. Abu Raddad
Dr. Hiam Chemitery
Weill Cornell Medicine – Qatar, Doha, Qatar
[email protected]

Roberto Bertorini, MD, MPH
Ministry of Public Health, Doha, Qatar

For the National Study Group for COVID-19 Vaccination

This letter was published on January 19, 2022 on NEJM.org.