Two-dose SARS-CoV-2 vaccine effectiveness against infection and hospitalization in Canada

In December 2020, two mRNA vaccines were approved for use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Canada, the BNT162b2 (Pfizer-BioNTech) and the mRNA-1273 (Moderna). Also authorized for use was the chimpanzee adenoviral vectored (ChAdOx1) vaccine (AstraZeneca) in February 2021. Both mRNA-based vaccines were scheduled to be administered via two doses, with three-week intervals for the BNT162b2 vaccine and four weeks for the mRNA-1273 vaccine. The ChAdOx1 vaccine was scheduled to be administered via two doses with an interval between doses of 4-12 weeks.

Study: Two-dose SARS-CoV-2 vaccine effectiveness with mixed schedules and extended dosing intervals: test-negative design studies from British Columbia and Quebec, Canada. Image Credit: JLStock/ Shutterstock

A second dose-deferral approach was implemented in March 2021 by Canada’s National Advisory Committee on Immunization (NACI), which recommended an extension in the interval between the first and second dose of vaccine of up to 16 weeks. Healthcare workers and residents of long-term care facilities (LTCF) were prioritized for the first doses of SARS-CoV-2 vaccines within British Columbia (BC) and Quebec. In March 2021, vaccination began of community-dwelling adults, progressing sequentially to younger age groups.

In this study, authors from varying Canadian institutes report on two-dose vaccine effectiveness (VE) against infection and hospitalization, which includes infection from the Delta variant of concern (VOC) in BC and Quebec.

A preprint version of this study, which is yet to undergo peer review, is available on the medRxiv* preprint server.

The study

The authors collected 380,532 specimens to analyze VE in BC, of which 27,439 were test-positive cases, and 1582 were from hospitalized cases. There was a total of 854,915 cases collected from Quebec, of which 17,234 were test-positive cases, and 878 were hospitalized cases. The Delta variant made up 91% of the cases in BC and 85% of cases in Quebec.

The VE with both doses of the mRNA-based vaccines was 90% in BC and 88% in Quebec. The VE of the ChAdOx1 vaccine was significantly lower in recipients who received two doses, with 71% in BC and 73% in Quebec. However, VE was significantly improved in individuals who received a mixed schedule of mRNA-based and the ChAdOx1 vaccine, with 90% in BC and 87% in Quebec.

VE against hospitalization with two doses of the mRNA-based vaccines was 98% in BC and 97% in Quebec and was similar for the ChAdOx1 vaccine with 94% in BC and 94% in Quebec. Similar levels of VE were also shown in recipients of mixed mRNA or mixed ChAdOx1/mRNA doses. The VE for both vaccine types against the Delta variant was almost identical to the overall analysis and was similar among the other VOCs.

The two-dose VE against hospitalization with the mRNA-based vaccines in BC and Quebec remained ≥95% seven months post-vaccination. The VE against infection with the mRNA-based vaccines peaked at 2-3 weeks post-vaccination at 90% but remained at 80% eight months post-vaccination. Recipients of the homologous two-dose ChAdOx1 vaccine showed VE of ≥70%, which was maintained for at least four months post-vaccination. None of the results collected indicated a greater decline in VE against the Delta variant.

VE of the mRNA-based vaccines was improved when there were longer intervals between the first and second doses. With the proposed interval specified by the manufacturers of 3-4 weeks, VE in BC was 85% and 79% in Quebec. VE against hospitalizations was observed to be greater with a 7-8 week interval (99%) when compared to a 3-4 week interval (93%).

Due to a shorter interval between vaccines meaning there would have been a longer time since the second dose when the samples were collected, the authors explored VE stratified simultaneously for period effects. When the second dose was administered ≥7- as opposed to 3-4 weeks after the first, the increased VE of 5-10% was maintained at all time points since the second dose.

Implications

The results from this study demonstrated that two doses of mRNA-based and/or ChAdOx1 vaccines provide robust protection against hospitalization, without minimal signs of decline 5-7 months post-vaccination in community-dwelling adults. These vaccines were also shown to provide sustained protection against VOCs, including the Delta variant.

There was a slight decline in VE against infection observed from the peak of 90%, but it remained approximately 80% seven months post-vaccination. VE was shown to be improved when the interval between the first and second dose was extended. These results support mixed SARS-CoV-2 vaccine schedules and the extension of intervals between the first and second doses, each of which could improve vaccine coverage globally.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Colin Lightfoot

Colin graduated from the University of Chester with a B.Sc. in Biomedical Science in 2020. Since completing his undergraduate degree, he worked for NHS England as an Associate Practitioner, responsible for testing inpatients for COVID-19 on admission.