Pfizer-BioNTech mRNA BNT162b2 Covid-19 vaccine protection against variants of concern after one versus two doses

Abstract

Strategies for rolling out vaccination against Coronavirus Disease 2019 (Covid-19) varied across countries. A key question is whether delaying administration of the second vaccine dose to vaccinate the largest number of people in the shortest time, in situations of limited vaccine supplies and high incidence, could avert more disease cases, hospitalizations and deaths than the current protocol of a second dose shortly after the first dose. The messenger RNA vaccine BNT162b2 (Pfizer-BioNTech) effectiveness against infection and against disease in the weeks following the first dose. Error bars indicate the 95% confidence intervals for vaccine effectiveness estimates. The messenger RNA vaccine BNT162b2 (Pfizer-BioNTech) effectiveness against infection and against disease in the weeks following vaccination with the first dose aVaccine effectiveness was estimated using the test-negative, case–control study design.2 Cases and controls were matched one-to-one by age, sex, nationality, and reason for PCR testing. Vaccine effectiveness is given by2 |$\mathrm{Vaccine}\ \mathrm{effectiveness}=1-\frac{\mathrm{vaccinated}\ \mathrm{among}\ \mathrm{cases}\times \mathrm{unvaccinated}\ \mathrm{among}\ \mathrm{controls}}{\mathrm{vaccinated}\ \mathrm{among}\ \mathrm{controls}\times \mathrm{unvaccinated}\ \mathrm{among}\ \mathrm{cases}}$|⁠. bAny B.1.1.7 PCR-confirmed infection. A B.1.1.7 infection is proxied as an S-gene ‘target failure’ case using the TaqPath COVID-19 Combo Kit platform (Thermo Fisher Scientific, USA), applying the criterion of PCR cycle threshold value ≤ 30 for both the N and ORF1ab genes, but a negative outcome for the S-gene. The median date of vaccination was March 1 2021 for the cases and February 28 2021 for their matched controls. cAny B.1.351 PCR-confirmed infection. With only B.1.351 and B.1.1.7 cases identified in the viral genome sequencing after 7 March 2021, a B.1.351 infection is proxied as the complement of the B.1.1.7 criterion, that is any infection with a Ct value ≤ 30 for the N, ORF1ab and S genes between March 8 and 31 2021. The median date of vaccination was March 7 2021 for the cases and March 1 2021 for their matched controls. dAny B.1.1.7 PCR-confirmed infection that led to severe, critical or fatal disease. Severe disease, critical disease and COVID-19 death were defined based on the World Health Organization criteria for classifying SARS-CoV-2 infection severity3 and COVID-19-related death.4 eAny B.1.351 PCR-confirmed infection that led to severe, critical or fatal disease. Severe disease, critical disease and COVID-19 death were defined based on the World Health Organization criteria for classifying SARS-CoV-2 infection severity3 and COVID-19-related death.4 fAny PCR-confirmed infection that led to severe, critical or fatal disease. With the dominance of both B.1.1.7 and B.1.351 variants during the study period, this effectiveness is a combined measure against both of these variants. Severe disease, critical disease and COVID-19 death were defined based on the World Health Organization criteria for classifying SARS-CoV-2 infection severity3 and COVID-19-related death.4 BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Qatar was recently reported with focus on individuals who completed 14 days after the second dose.1 Here, we provide a follow-up analysis of how vaccine protection develops week-by-week after the first dose. Data for SARS-CoV-2 were extracted from Qatar’s nationwide digital-health information platform. The platform hosts the national centralized SARS-CoV-2 databases that captured all vaccination records, polymerase chain reaction (PCR) testing, and COVID-19 hospitalizations and deaths since epidemic start.1 The study was conducted from 1 February to 31 March 2021, the period of rapid mass vaccination scale-up. Vaccine effectiveness was estimated using the test-negative case–control study design.2 Cases and controls were matched one-to-one by age, sex, nationality and reason for PCR testing. Effectiveness was estimated against documented infection with the B.1.1.7 or B.1.351 variants, as well as against severe, critical or fatal disease due to any SARS-CoV-2 infection. Classification of COVID-19 case severity (acute-care hospitalizations),3 criticality (ICU hospitalizations)3 and fatality4 followed the World Health Organization guidelines. Further details on study methods can be found in our previous publication.1 Between 1 February and 31 March 2021, 333 764 individuals received at least one BNT162b2 vaccine dose, of whom 250 619 completed two doses. Two-thirds (60.8%) of those vaccinated were men, and the median age was 40 years. Median time elapsed between the first and second doses was 21 days, and 98.4% of individuals received their second dose ≤ 25 days after the first dose. Effectiveness against infection with B.1.1.7 or B.1.351 was negligible for 2 weeks after the first dose (Figure 1). E