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

Chung H, Austin PC, Brown KA, Buchan SA, Fell DB, Fong C, Gubbay JB, Nasreen S, Schwartz KL, Sundaram ME, Tadrous M, Wilson K, Wilson SE, Kwong JC; on behalf of the Canadian Immunization Research Network (CIRN) Provincial Collaborative Network (PCN) Investigators. Open Forum Infect Dis. 2022; Sep 7 [Epub ahead of print]. DOI:

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.

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