Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants

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.

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

Vaccine Effectiveness against Infection and against Disease in Qatar.

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.

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%.

Laith J. Abu-Raddad, Ph.D.
Hiam Chemaitelly, M.Sc.
Weill Cornell Medicine–Qatar, Doha, Qatar
[email protected]

Adeel A. Butt, M.D.
Hamad Medical Corporation, Doha, Qatar

for the National Study Group for COVID-19 Vaccination

Supported by the Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core at Weill Cornell Medicine–Qatar; the Ministry of Public Health; and Hamad Medical Corporation. The Qatar Genome Program supported the viral genome sequencing.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

This letter was published on May 5, 2021, at NEJM.org.

Members of the National Study Group for COVID-19 Vaccination are listed in the Supplementary Appendix, available with the full text of this letter at NEJM.org.

  1. 1. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:26032615.

  2. 2. Jackson ML, Nelson JC. The test-negative design for estimating influenza vaccine effectiveness. Vaccine 2013;31:21652168.

  3. 3. COVID-19 clinical management: living guidance. Geneva: World Health Organization, January 25, 2021 (https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1).

  4. 4. Dagan N, Barda N, Kepten E, et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med 2021;384:14121423.

  5. 5. Thompson MG, Burgess JL, Naleway AL, et al. Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines in preventing SARS-CoV-2 infection among health care personnel, first responders, and other essential and frontline workers — eight U.S. locations, December 2020–March 2021. MMWR Morb Mortal Wkly Rep 2021;70:495500.

Vaccine Effectiveness against Infection and against Disease in Qatar.

Type of Infection or Disease PCR-Positive Persons PCR-Negative Persons Effectiveness (95% CI)*
Vaccinated Unvaccinated Vaccinated Unvaccinated
number of persons percent
PCR-confirmed infection with the B.1.1.7 variant†
After one dose 892 18,075 1241 17,726 29.5 (22.9–35.5)
≥14 days after second dose 50 16,354 465 15,939 89.5 (85.9–92.3)
PCR-confirmed infection with the B.1.351 variant‡
After one dose 1329 20,177 1580 19,926 16.9 (10.4–23.0)
≥14 days after second dose 179 19,396 698 18,877 75.0 (70.5–78.9)
Severe, critical, or fatal disease caused by the B.1.1.7 variant
After one dose 30 468 61 437 54.1 (26.1–71.9)
≥14 days after second dose 0 401 20 381 100.0 (81.7–100.0)
Severe, critical, or fatal disease caused by the B.1.351 variant
After one dose 45 348 35 358 0.0 (0.0–19.0)
≥14 days after second dose 0 300 14 286 100.0 (73.7–100.0)
Severe, critical, or fatal disease caused by any SARS-CoV-2
After one dose 139 1,966 220 1,885 39.4 (24.0–51.8)
≥14 days after second dose 3 1,692 109 1,586 97.4 (92.2–99.5)