Two-Dose Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Effectiveness With Mixed Schedules and Extended Dosing Intervals: Test-Negative Design Studies From British Columbia and Quebec, Canada

Background. The Canadian coronavirus disease 2019 (COVID-19) immunization strategy deferred second doses and allowed mixed schedules. We compared 2-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in 2 of Canada’s larger provinces. Methods. Two-dose VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or hospitalization among adults ≥ 18 years, including due to Alpha, Gamma, and Delta variants of concern (VOCs), was assessed ≥ 14 days postvaccination by test-negative design studies separately conducted in British Columbia and Quebec, Canada, between 30 May and 27 November (epi-weeks 22–47) 2021. Results. In both provinces, all homologous or heterologous mRNA and/or ChAdOx1 2-dose schedules were associated with ≥ 90% reduction in SARS-CoV-2 hospitalization risk for ≥ 7 months. With slight decline from a peak of . 90%, VE against infection was ≥ 80% for ≥ 6 months following homologous mRNA vaccination, lower by ≏ 10% when both doses were ChAdOx1 but comparably high following heterologous ChAdOx1 + mRNA receipt. Findings were similar by age group, sex, and VOC. VE was significantly higher with longer 7–8-week versus manufacturer-specified 3–4-week intervals between mRNA doses. Conclusions