SARS-CoV-2 mRNA vaccine effectiveness in healthcare workers by dosing interval and time since vaccination: test negative design, British Columbia, Canada

Abstract Background One- and two-dose mRNA vaccine effectiveness (VE) estimates against SARS-CoV-2 infection by dosing interval and time since vaccination were assessed among healthcare workers (HCWs) in publicly-funded acute and community (non-residential) healthcare facilities in British Columbia, Canada. Methods A test-negative design was used with (6:1) controls matched to cases on epidemiological week of SARS-CoV-2 test date. mRNA vaccination was defined by receipt of the first dose ≥21 days or second dose ≥14 days before test date. HCWs ≥18 years old tested for SARS-CoV-2 between epi-weeks 3-39 (January 17-October 2,2021) were included, when varying dosing intervals and a mix of circulating variants-of-concern contributed, including Delta dominance provincially from epi-week 31 (August 1). Results Single- and two-dose analyses included 1,265 and 1,246 cases, respectively. Median follow-up period was 49 days (interquartile range: 34-69) for single-dose and 89 days (interquartile range: 61-123) for two-dose recipients, with 12%, 31% and 58% of second doses given 3-5, 6 or ≥7 weeks after the first. Adjusted mRNA VE against SARS-CoV-2 was 71% [95% CI: 66, 76] for one dose and 90% [95% CI: 88, 92] for two doses, similar with two heterologous mRNA doses (92%;[95% CI: 86, 95]). Two-dose VE remained >80% at ≥28 weeks post-second dose. Two-dose VE was consistently 5-7% higher with ≥7-week versus 3-5-week interval between doses. Conclusions In a HCW population, we report substantial single-dose and strong and sustained two-dose mRNA vaccine protection, the latter maintained at least seven months. Findings inform longer interval between doses, with global health and equity implications.