Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar

N Engl J Med. 2021 Dec 9;385(24):e83. doi: 10.1056/NEJMoa2114114. Epub 2021 Oct 6.


Background: Waning of vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (Covid-19) is a concern. The persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the B.1.351 (or beta) and B.1.617.2 (or delta) variants have dominated incidence and polymerase-chain-reaction testing is done on a mass scale, is unclear.

Methods: We used a matched test-negative, case-control study design to estimate vaccine effectiveness against any SARS-CoV-2 infection and against any severe, critical, or fatal case of Covid-19, from January 1 to September 5, 2021.

Results: Estimated BNT162b2 effectiveness against any SARS-CoV-2 infection was negligible in the first 2 weeks after the first dose. It increased to 36.8% (95% confidence interval [CI], 33.2 to 40.2) in the third week after the first dose and reached its peak at 77.5% (95% CI, 76.4 to 78.6) in the first month after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating after the fourth month to reach approximately 20% in months 5 through 7 after the second dose. Effectiveness against symptomatic infection was higher than effectiveness against asymptomatic infection but waned similarly. Variant-specific effectiveness waned in the same pattern. Effectiveness against any severe, critical, or fatal case of Covid-19 increased rapidly to 66.1% (95% CI, 56.8 to 73.5) by the third week after the first dose and reached 96% or higher in the first 2 months after the second dose; effectiveness persisted at approximately this level for 6 months.

Conclusions: BNT162b2-induced protection against SARS-CoV-2 infection appeared to wane rapidly following its peak after the second dose, but protection against hospitalization and death persisted at a robust level for 6 months after the second dose. (Funded by Weill Cornell Medicine-Qatar and others.).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273
  • Adult
  • Aged
  • BNT162 Vaccine / immunology*
  • COVID-19 / epidemiology
  • COVID-19 / immunology
  • COVID-19 / mortality
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines
  • Case-Control Studies
  • Female
  • Humans
  • Immunization, Secondary
  • Immunogenicity, Vaccine*
  • Male
  • Middle Aged
  • Qatar / epidemiology
  • Time Factors
  • Vaccine Efficacy*
  • Young Adult


  • COVID-19 Vaccines
  • 2019-nCoV Vaccine mRNA-1273
  • BNT162 Vaccine

Supplementary concepts

  • COVID-19 breakthrough infections