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To The Editor: The messenger RNA vaccine BNT162b2 (Pfizer–BioNTech) has 95% efficacy against coronavirus disease 2019 (Covid-19).1 Qatar launched a mass immunization campaign with this vaccine on December 21, 2020. As of March 31, 2021, a total of 385,853 persons had received at least one vaccine dose and 265,410 had completed the two doses. Vaccination scale-up occurred as Qatar was undergoing its second and third waves of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which were triggered by expansion of the B.1.1.7 variant (starting in mid-January 2021) and the B.1.351 variant (starting in mid-February 2021). The B.1.1.7 wave peaked during the first week of March, and the rapid expansion of B.1.351 started in mid-March and continues to the present day. Viral genome sequencing conducted from February 23 through March 18 indicated that 50.0% of cases of Covid-19 in Qatar were caused by B.1.351 and 44.5% were caused by B.1.1.7. Nearly all cases in which virus was sequenced after March 7 were caused by either B.1.351 or B.1.1.7.

id-March and continues to the present day. Viral genome sequencing conducted from February 23 through March 18 indicated that 50.0% of cases of Covid-19 in Qatar were caused by B.1.351 and 44.5% were caused by B.1.1.7. Nearly all cases in which virus was sequenced after March 7 were caused by either B.1.351 or B.1.1.7. Data on vaccinations, polymerase-chain-reaction testing, and clinical characteristics were extracted from the national, federated Covid-19 databases that have captured all SARS-CoV-2–related data since the start of the epidemic (Section S1 of the Supplementary Appendix, available with the full text of this letter at NEJM.org). Vaccine effectiveness was estimated with a test-negative case–control study design, a preferred design for assessing vaccine effectiveness against influenza (see the Supplementary Appendix).2 A key strength of this design is the ability to control for bias that may result from differences in health care–seeking behavior between vaccinated and unvaccinated persons.2

-negative case–control study design, a preferred design for assessing vaccine effectiveness against influenza (see the Supplementary Appendix).2 A key strength of this design is the ability to control for bias that may result from differences in health care–seeking behavior between vaccinated and unvaccinated persons.2 The estimated effectiveness of the vaccine against any documented infection with the B.1.1.7 variant was 89.5% (95% confidence interval [CI], 85.9 to 92.3) at 14 or more days after the second dose (Table 1 and Table S2). The effectiveness against any documented infection with the B.1.351 variant was 75.0% (95% CI, 70.5 to 78.9). Vaccine effectiveness against severe, critical, or fatal disease due to infection with any SARS-CoV-2 (with the B.1.1.7 and B.1.351 variants being predominant within Qatar) was very high, at 97.4% (95% CI, 92.2 to 99.5). Sensitivity analyses confirmed these results (Table S3). Vaccine effectiveness was also assessed with the use of a cohort study design by comparing the incidence of infection among vaccinated persons with the incidence in the national cohort of persons who were antibody-negative (Section S2). Effectiveness was estimated to be 87.0% (95% CI, 81.8 to 90.7) against the B.1.1.7 variant and 72.1% (95% CI, 66.4 to 76.8) against the B.1.351 variant, findings that confirm the results reported above.

mong vaccinated persons with the incidence in the national cohort of persons who were antibody-negative (Section S2). Effectiveness was estimated to be 87.0% (95% CI, 81.8 to 90.7) against the B.1.1.7 variant and 72.1% (95% CI, 66.4 to 76.8) against the B.1.351 variant, findings that confirm the results reported above. The BNT162b2 vaccine was effective against infection and disease in the population of Qatar, despite the B.1.1.7 and B.1.351 variants being predominant within the country; however, vaccine effectiveness against the B.1.351 variant was approximately 20 percentage points lower than the effectiveness (>90%) reported in the clinical trial1 and in real-world conditions in Israel4 and the United States.5 In Qatar, as of March 31, breakthrough infections have been recorded in 6689 persons who had received one dose of the vaccine and in 1616 persons who had received two doses. Seven deaths from Covid-19 have been also recorded among vaccinated persons: five after the first dose and two after the second dose. Nevertheless, the reduced protection against infection with the B.1.351 variant did not seem to translate into poor protection against the most severe forms of infection (i.e., those resulting in hospitalization or death), which was robust, at greater than 90%.