To the editor:
Growing evidence suggests that vaccines against coronavirus disease 2019 (Covid-19) differ in efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or severe Covid-19,1-3 but data from controlled studies that include head-to-head comparisons of the immunity induced by these vaccines are lacking. We conducted a study to compare the protection afforded by the mRNA-1273 (Moderna) vaccine with that of the BNT162b2 (Pfizer-BioNTech) vaccine in Qatar.
Using data from national Covid-19 electronic health databases, we designed two matched retrospective cohort studies to mimic a randomized, controlled trial and to assess the incidence of documented SARS-CoV-2 infection after the first and second doses of mRNA. 1273 and BNT162b2 vaccines. Both studies involved the same population of individuals who had received the mRNA-1273 or BNT162b2 vaccines between 21 December 2020 and 20 October 2021 (see section S1 of the supplementary supplement, available in full text of this letter at NEJM.org). Individuals were matched one to one according to calendar week for vaccination and other variables, and the matched cohorts excluded individuals who had a confirmed SARS-CoV-2 infection prior to vaccination.
A total of 192,123 individuals who had received two doses of mRNA-1273 vaccine were matched with the same number of individuals who had received two doses of BNT162b2 vaccine (Fig. S1, Table S3 and Section S5). Among the mRNA-1273 vaccinated individuals, 878 breakthrough infections were detected after the second dose at a median follow-up of 89 days. Of these infections, 3 developed into severe Covid-19 (acute hospitalization), but none developed into critical illness (intensive care unit) or death.
The cumulative incidence of second-degree breakthrough infections in matched cohorts of mRNA-1273-vaccinated and BNT162b2-vaccinated individuals is shown. CI denotes confidence interval and SARS-CoV-2 severe acute respiratory syndrome coronavirus 2.
Among BNT162b2 vaccinated individuals, 1262 breakthrough infections were recorded after the second dose at a median follow-up of 86 days. Of these infections, 7 developed into severe Covid-19, none to critical illness and 1 to death. In both vaccinated cohorts, breakthrough infections tended to occur among individuals with a longer interval since the time of vaccination (figure 1 and Table S5).
The difference between the two vaccine cohorts in the incidence of documented infection started during the third week after the first dose (Fig. S2). The incidence of SARS-CoV-2 infection and severe Covid-19 was lower among mRNA-1273 vaccinated individuals than among BNT162b2 vaccinated individuals after only one dose (section S5). At 6 months follow-up after the second dose, the estimated cumulative incidence of breakthrough infection was 0.59% (95% confidence interval) [CI], 0.55 to 0.64) among those who received the mRNA-1273 vaccine and 0.84% (95% CI, 0.79 to 0.89) among those who received the BNT162b2 vaccine (figure 1). 90 days after the second dose, during a period of low incidence of infection in Qatar, both incidence curves began to bend upwards,2.4 which indicated a progressive decline in vaccine protection.4
The estimated overall adjusted hazard ratio for infection after the second dose of mRNA-1273 vaccine, compared to the second dose of BNT162b2 vaccine, was 0.69 (95% CI, 0.63 to 0.75). The adjusted hazard ratio was largely stable over time after the second dose at approx. this value (figure 1). The estimated overall adjusted hazard ratio for severe, critical or fatal 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 infection than vaccination with BNT162b2; this finding is consistent with the differences in neutralizing antibody titers.5 However, both vaccines induced strong protection against Covid-19-related hospitalization and death. Both vaccines also had remarkably similar patterns of protection building, starting from the first dose and then decreasing a few months after the second dose. The nature of vaccine immunity, which builds up after vaccination and decreases over time, appeared to be similar in both vaccines.
Laith J. Abu-Raddad, Ph.D.
Hiam Chemaitelly, Ph.D.
Weill Cornell Medicine – Qatar, Doha, Qatar
Roberto Bertollini, MD, MPH
Ministry of Public Health, Doha, Qatar
for the National Study Group on COVID-19 Vaccination
Information forms provided by the authors are available with the full text of this letter at NEJM.org.
This letter was published on January 19, 2022 on NEJM.org.
Members of the National COVID-19 Vaccination Research Group are listed in the Supplementary Appendix, which is available in full text of this letter at NEJM.org.
1. International Vaccine Access Center. VIEW hub: Covid-19 data, vaccine studies, efficacy studies. 2021 (https://view-hub.org/covid-19/effectiveness-studies/).
2. Abu-Raddad LJ, Chemaitelly H, Ayoub HHet al. Combination of previous SARS-CoV-2 infection with risk of breakthrough infection following mRNA vaccination in Qatar. JAMA 2021; 326:1930–1939.
3. Rothschild V, Hirsh-Raccah B, poor me, Muszkat M, Matok I. Comparison of the clinical efficacy of COVID-19 vaccines: a systematic review and network meta-analysis. Sci Rep 2021; 11:22777–22777.
4. Chemaitelly H, Tang P, Hasan MRet al. Decreasing BNT162b2 vaccine protection against SARS-CoV-2 infection in Qatar. N Engl J Med 2021385 (24):e83–e83.
5. Khoury DS, Cromer D, Reynaldi Aet al. Neutralizing antibody levels are highly predictive of immune protection against symptomatic SARS-CoV-2 infection. Nat Med 2021; 27:1205–1211.
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