Effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes in Ontario, Canada: a test-negative design study

ABSTRACT Objectives To estimate the effectiveness of mRNA COVID-19 vaccines against symptomatic infection and severe outcomes. Design We applied a test-negative design study to linked laboratory, vaccination, and health administrative databases, and used multivariable logistic regression adjusting for demographic and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness (VE) against symptomatic infection and severe outcomes. Setting Ontario, Canada between 14 December 2020 and 19 April 2021. Participants Community-dwelling adults aged ≥16 years who had COVID-19 symptoms and were tested for SARS-CoV-2. Interventions Pfizer-BioNTech’s BNT162b2 or Moderna’s mRNA-1273 vaccine. Main outcome measures Laboratory-confirmed SARS-CoV-2 by RT-PCR; hospitalization/death associated with SARS-CoV-2 infection. Results Among 324,033 symptomatic individuals, 53,270 (16.4%) were positive for SARS-CoV-2 and 21,272 (6.6%) received ≥1 vaccine dose. Among test-positive cases, 2,479 (4.7%) had a severe outcome. VE against symptomatic infection ≥14 days after receiving only 1 dose was 60% (95%CI, 57 to 64%), increasing from 48% (95%CI, 41 to 54%) at 14–20 days after the first dose to 71% (95%CI, 63 to 78%) at 35–41 days. VE ≥7 days after 2 doses was 91% (95%CI, 89 to 93%). Against severe outcomes, VE ≥14 days after 1 dose was 70% (95%CI, 60 to 77%), increasing from 62% (95%CI, 44 to 75%) at 14–20 days to 91% (95%CI, 73 to 97%) at ≥35 days, whereas VE ≥7 days after 2 doses was 98% (95%CI, 88 to 100%). For adults aged ≥70 years, VE estimates were lower for intervals shortly after receiving 1 dose, but were comparable to younger adults for all intervals after 28 days. After 2 doses, we observed high VE against E484K-positive variants. Conclusions Two doses of mRNA COVID-19 vaccines are highly effective against symptomatic infection and severe outcomes. Single-dose effectiveness is lower, particularly for older adults shortly after the first dose.