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: Two doses of any mRNA and/or ChAdOx1 combination gave substantial and sustained protection against SARS-CoV-2 hospitalization, spanning Delta-dominant circulation. ChAdOx1 VE against infection was improved by heterologous mRNA series completion. A 7-8-week interval between first and second doses improved mRNA VE and may be the optimal schedule outside periods of intense epidemic surge. Findings support interchangeability and extended intervals between SARS-CoV-2 vaccine doses, with potential global implications for low-coverage areas and, going forward, for children.

SARS-CoV-2 mRNA Vaccine Effectiveness in Health Care Workers by Dosing Interval and Time Since Vaccination: Test-Negative Design, British Columbia, Canada.

Background: One- and two-dose mRNA vaccine effectiveness (VE) estimates against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by dosing interval and time since vaccination were assessed among healthcare workers (HCWs) in publicly funded acute and community (nonresidential) healthcare facilities in British Columbia, Canada. Methods: A test-negative design was used with controls matched to cases (6:1) 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 the test date. HCWs ≥18 years old tested for SARS-CoV-2 between epi-weeks 3 and 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 1265 and 1246 cases, respectively. The median follow-up period (interquartile range) was 49 (34-69) days for single-dose and 89 (61-123) days 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 to 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 a ≥7-week vs 3-5-week interval between doses, but with overlapping confidence intervals. Conclusions: Among HCWs, we report substantial single-dose and strong and sustained two-dose mRNA vaccine protection, with the latter maintained for at least 7 months. These findings support a longer interval between doses, with global health and equity implications.

Comparative Single-Dose mRNA and ChAdOx1 Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2, Including Variants of Concern: Test-Negative Design, British Columbia, Canada.

BACKGROUND: In British Columbia, Canada, most adults 50-69 years old became eligible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in April 2021, with chimpanzee adenoviral vectored vaccine (ChAdOx1) restricted to ≥55-year-olds and second doses deferred ≥6 weeks to optimize single-dose coverage. METHODS: Among adults 50-69 years old, single-dose messenger RNA (mRNA) and ChAdOx1 vaccine effectiveness (VE) against SARS-CoV-2 infection and hospitalization, including variant-specific, was assessed by test-negative design between 4 April and 2 October 2021. RESULTS: Single-dose VE included 11 861 cases and 99 544 controls. Median of postvaccination follow-up was 32 days (interquartile range, 15-52 days). Alpha, Gamma, and Delta variants comprised 23%, 18%, and 56%, respectively, of genetically characterized viruses. At 21-55 days postvaccination, single-dose mRNA and ChAdOx1 VE (95% confidence interval [CI]) was 74% (71%-76%) and 59% (53%-65%) against any infection and 86% (80%-90%) and 94% (85%-97%) against hospitalization, respectively. VE (95% CI) was similar against Alpha and Gamma infections for mRNA (80% [76%-84%] and 80% [75%-84%], respectively) and ChAdOx1 (69% [60%-76%] and 66% [56%-73%], respectively). mRNA VE was lower at 63% (95% CI, 56%-69%) against Delta but 85% (95% CI, 71%-92%) against Delta-associated hospitalization (nonestimable for ChAdOx1). CONCLUSIONS: A single mRNA or ChAdOx1 vaccine dose gave important protection against SARS-CoV-2, including early variants of concern. ChAdOx1 VE was lower against infection, but 1 dose of either vaccine reduced the hospitalization risk by >85% to at least 8 weeks postvaccination. Findings inform program options, including longer dosing intervals.

Single-dose mRNA Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Including Alpha and Gamma Variants: A Test-negative Design in Adults 70 Years and Older in British Columbia, Canada.

BACKGROUND: Randomized-controlled trials of messenger RNA (mRNA) vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) included relatively few elderly participants. We assess single-dose mRNA vaccine effectiveness (VE) in adults ≥ 70 years old in British Columbia, Canada, where second doses were deferred by up to 16 weeks and where a spring 2021 wave uniquely included codominant circulation of Alpha (B.1.1.7) and Gamma (P.1) variants of concern (VOC). METHODS: Analyses included community-dwelling adults ≥ 70 years old with specimen collection between 4 April (epidemiological week 14) and 1 May (week 17) 2021. Adjusted VE was estimated by test-negative design. Cases were reverse-transcription polymerase chain reaction (RT-PCR) test-positive for SARS-CoV-2, and controls were test-negative. Vaccine status was defined by receipt of a single-dose ≥ 21 days before specimen collection, but a range of intervals was assessed. Variant-specific VE was estimated against viruses genetically characterized as Alpha, Gamma or non-VOC lineages. RESULTS: VE analyses included 16 993 specimens: 1226 (7%) test-positive cases and 15 767 test-negative controls. Of 1131 (92%) genetically characterized viruses, 509 (45%), 314 (28%), and 276 (24%) were Alpha, Gamma, and non-VOC lineages, respectively. At 0-13 days postvaccination, VE was negligible at 14% (95% confidence interval [CI], 0-26) but increased from 43% (95% CI, 30-53) at 14-20 days to 75% (95% CI, 63-83) at 35-41 days postvaccination. VE at ≥ 21 days postvaccination was 65% (95% CI, 58-71) overall: 72% (95% CI, 58-81), 67% (95% CI, 57-75), and 61% (95% CI, 45-72) for non-VOC, Alpha, and Gamma variants, respectively. CONCLUSIONS: A single dose of mRNA vaccine reduced the risk of SARS-CoV-2 by about two-thirds in adults ≥ 70 years old, with protection only minimally reduced against Alpha and Gamma variants.

Influenza Vaccine Does Not Increase the Risk of Coronavirus or Other Noninfluenza Respiratory Viruses: Retrospective Analysis From Canada, 2010-2011 to 2016-2017.

Influenza vaccine effectiveness against influenza and noninfluenza respiratory viruses (NIRVs) was assessed by test-negative design using historic datasets of the community-based Canadian Sentinel Practitioner Surveillance Network, spanning 2010-2011 to 2016-2017. Vaccine significantly reduced the risk of influenza illness by >40% with no effect on coronaviruses or other NIRV risk.