Effectiveness of COVID-19 vaccines over time prior to Omicron emergence in Ontario, Canada: test-negative design study

Background — Waning protection from two doses of COVID-19 vaccines led to third dose availability in multiple countries even prior to emergence of the Omicron variant.

Methods — We used the test-negative study design to estimate vaccine effectiveness (VE) against any SARS-CoV-2 infection, symptomatic infection, and severe outcomes (COVID-19-related hospitalizations or death) by time since second dose of any combination of BNT162b2, mRNA-1273, and ChAdOx1 between 11 January and 21 November 2021 for subgroups based on patient and vaccine characteristics.

Results — We included 261,360 test-positive cases (of any SARS-CoV-2 lineage) and 2,783,699 individuals as test-negative controls. VE of two mRNA vaccine doses decreased from 90% (95%CI, 90-90%) 7-59 days after the second dose to 75% (95%CI, 72-78%) after ≥240 days against infection, from 94% (95%CI, 84-95%) to 87% (95%CI, 85-89%) against symptomatic infection, and remained stable (98% [95%CI, 97-98%] to 98% [95%CI, 96-99%])against severe outcomes. Similar trends were seen with heterologous ChAdOx1 and mRNA vaccine schedules. VE estimates for dosing intervals <35 days were lower than for longer intervals (e.g., VE of two mRNA vaccines against symptomatic infection at 120-179 days was 86% [95%CI, 85-88%] for dosing intervals <35 days, 92% [95%CI, 91-93%] for 35-55 days, and 91% [95%CI, 90-92%] for ≥56 days), but when stratified by age group and subperiod, there were no differences between dosing intervals.

Conclusions — Prior to Omicron emergence, VE of any two-dose primary series, including heterologous schedules and varying dosing intervals, decreased over time against any infection and symptomatic infection but remained high against severe outcomes.