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

Abstract

Background The Canadian COVID-19 immunization strategy deferred second doses and allowed mixed schedules. We compared two-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in two of Canada’s larger provinces. Methods Two-dose VE against SARS-CoV-2 infection or hospitalization among adults ≥18-years-old, including due to Alpha, Gamma and Delta variants of concern (VOC), was assessed at ≥14 days post-vaccination by test-negative design studies separately conducted in British Columbia and Quebec, Canada between May 30 and November 27 (epi-weeks 22-47), 2021. Results In both provinces, all homologous or heterologous mRNA and/or ChAdOx1 two-dose schedules were associated with ≥90% reduction in SARS-CoV-2 hospitalization risk for at least 7 months. With slight decline from a peak of >90%, VE against infection was ≥80% for at least 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 vs. manufacturer-specified 3–4-week interval 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.

Short term, relative effectiveness of four doses versus three doses of BNT162b2 vaccine in people aged 60 years and older in Israel: retrospective, test negative, case-control study

“…Nonetheless, a growing number of studies suggest that an extended dosing interval amplifies both the humoral immune response 30 and perhaps the cellular response, 31 and is an effective global strategy given the discrepancies between regions with high and low vaccination coverage. 32 But even recent studies have so far only investigated the second dose and have not evaluated responses to the omicron variant. 30 33 Our present analysis showed that receiving the third dose later (that is, after August 2021) was associated with slight protection against infection, but was not significantly associated with the odds of hospital admission or death related to covid-19.…”

Protection against Omicron re-infection conferred by prior heterologous SARS-CoV-2 infection, with and without mRNA vaccination

“…Second doses were deferred up to 16 weeks with third doses also beginning with the oldest in December 2021 ( Supplementary Figure 1 ). 10,11…”

Role of COVID-19 Vaccines in SARS-CoV-2 Variants

“…The negative test case–control study from Canada showed that AZD1222 against documented infection for Gamma was surprisingly effective ( 50 ). However, the study from Brazil revealed that the VE of double-dose AstraZeneca-Vaxzevria vaccine was 88.1% (95% CI: 82.8–91.7) ( 56 ) ( Table 3 ).…”

“…Peer-reviewed studies from Spain also demonstrated that AZD1222 was 55% (95% CI: 39–67) effective against documented infection for the Delta variant ( 41 ). The results of the negative test case–control study from Canada revealed that the VE against hospitalization due to Delta was >90% ≥14 days following the 2nd dose ( 50 ). Furthermore, the VE of AZD1222 against death caused by the Delta variant was 91% (95% CI: 86–94) in the evaluation of the VE of AZD1222 preventing death among 380,532 residents in British Columbia including 27,439 cases ≥14 days following the second dose ( 62 ) ( Table 3 ).…”