. 2021 Aug 20:374:n1943.

doi: 10.1136/bmj.n1943.

Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study

Hannah Chung¹, Siyi He¹, Sharifa Nasreen¹, Maria E Sundaram^{1

2}, Sarah A Buchan^{1

2

3

4}, Sarah E Wilson^{1

2

3

4}, Branson Chen¹, Andrew Calzavara¹, Deshayne B Fell^{1

5

6}, Peter C Austin^{1

7}, Kumanan Wilson^{5

8

9}, Kevin L Schwartz^{1

2

3}, Kevin A Brown^{1

2

3}, Jonathan B Gubbay^{3

10}, Nicole E Basta¹¹, Salaheddin M Mahmud¹², Christiaan H Righolt¹², Lawrence W Svenson^{13

14

15

16}, Shannon E MacDonald^{15

17}, Naveed Z Janjua^{18

19}, Mina Tadrous^{1

20

21}, Jeffrey C Kwong^{22

2

3

4

23

24}; Canadian Immunization Research Network (CIRN) Provincial Collaborative Network (PCN) Investigators

Affiliations

¹ ICES, Toronto, ON, Canada.
² Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
³ Public Health Ontario, ON, Canada.
⁴ Centre for Vaccine Preventable Diseases, University of Toronto, Toronto, ON, Canada.
⁵ School of Epidemiology and Public Health, University of Ottawa, ON, Canada.
⁶ Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
⁷ Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada.
⁸ Bruyère and Ottawa Hospital Research Institutes, Ottawa, ON, Canada.
⁹ Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹⁰ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
¹¹ Department of Epidemiology, Biostatistics, and Occupational Health, School of Population and Global Health, McGill University, Montreal, QC, Canada.
¹² Vaccine and Drug Evaluation Centre, Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
¹³ Analytics and Performance Reporting Branch, Alberta Health, Edmonton, AB, Canada.
¹⁴ Division of Preventive Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
¹⁵ School of Public Health, University of Alberta, Edmonton, AB, Canada.
¹⁶ Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
¹⁷ Faculty of Nursing, University of Alberta, Edmonton, AB, Canada.
¹⁸ British Columbia Centre for Disease Control, Vancouver, BC, Canada.
¹⁹ School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
²⁰ Women's College Hospital, Toronto, ON, Canada.
²¹ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
²² ICES, Toronto, ON, Canada jeff.kwong@utoronto.ca.
²³ Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
²⁴ University Health Network, Toronto, ON, Canada.

PMID: 34417165
PMCID: PMC8377789
DOI: 10.1136/bmj.n1943

Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study

Hannah Chung et al. BMJ. 2021.

. 2021 Aug 20:374:n1943.

doi: 10.1136/bmj.n1943.

Authors

Affiliations

¹ ICES, Toronto, ON, Canada.
² Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
³ Public Health Ontario, ON, Canada.
⁴ Centre for Vaccine Preventable Diseases, University of Toronto, Toronto, ON, Canada.
⁵ School of Epidemiology and Public Health, University of Ottawa, ON, Canada.
⁶ Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
⁷ Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada.
⁸ Bruyère and Ottawa Hospital Research Institutes, Ottawa, ON, Canada.
⁹ Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹⁰ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
¹¹ Department of Epidemiology, Biostatistics, and Occupational Health, School of Population and Global Health, McGill University, Montreal, QC, Canada.
¹² Vaccine and Drug Evaluation Centre, Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
¹³ Analytics and Performance Reporting Branch, Alberta Health, Edmonton, AB, Canada.
¹⁴ Division of Preventive Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
¹⁵ School of Public Health, University of Alberta, Edmonton, AB, Canada.
¹⁶ Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
¹⁷ Faculty of Nursing, University of Alberta, Edmonton, AB, Canada.
¹⁸ British Columbia Centre for Disease Control, Vancouver, BC, Canada.
¹⁹ School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
²⁰ Women's College Hospital, Toronto, ON, Canada.
²¹ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
²² ICES, Toronto, ON, Canada jeff.kwong@utoronto.ca.
²³ Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
²⁴ University Health Network, Toronto, ON, Canada.

PMID: 34417165
PMCID: PMC8377789
DOI: 10.1136/bmj.n1943

Abstract

Objective: To estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death).

Design: Test negative design study.

Setting: Ontario, Canada between 14 December 2020 and 19 April 2021.

Participants: 324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2.

Interventions: BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine.

Main outcome measures: Laboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes.

Results: Of 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation.

Conclusions: Two doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the Public Health Agency of Canada, the Canadian Institutes of Health Research, and Ontario’s Ministry of Health and Ministry of Long term Care for the submitted work. KW is chief executive officer of CANImmunize and serves on the data safety board for the Medicago covid-19 vaccine trial. SMM has received unrestricted research grants from Merck, GlaxoSmithKline, Sanofi Pasteur, Pfizer, and Roche-Assurex for unrelated studies. SMM has received fees as an advisory board member for GlaxoSmithKline, Merck, Pfizer, Sanofi Pasteur, and Seqirus. CHR has received an unrestricted research grant from Pfizer for an unrelated study.

Figures

**Fig 1**
Community dwelling people aged ≥16 years included in tested cohort between 14 December 2020 and 19 April 2021 in Ontario, Canada. *Recorded symptoms not consistent with covid-19 (eg, anxiety, cancer, falls). RT-PCR=reverse transcription polymerase chain reaction; ChAdOx1=Oxford-AstraZeneca vaccine

**Fig 2**
Unadjusted and adjusted vaccine effectiveness estimates of covid-19 mRNA vaccines (BNT162b2, mRNA-1273) against laboratory confirmed symptomatic SARS-CoV-2 infection by various intervals, between 14 December 2020 and 19 April 2021 in Ontario, Canada. Models were adjusted for age, sex, public health unit region, biweekly period of test, number of SARS-CoV-2 tests in the three months before 14 December 2020, presence of any comorbidity increasing the risk of severe covid-19, receipt of influenza vaccination in current or previous influenza season, and fifths of neighbourhood level household income, number of people in each dwelling, proportion of people employed as non-health essential workers, and self-identified visible minority

**Fig 3**
Unadjusted and adjusted vaccine effectiveness estimates of covid-19 mRNA vaccines (BNT162b2, mRNA-1273) against severe outcomes (hospital admission or death) associated with laboratory confirmed symptomatic SARS-CoV-2 infection by various intervals, between 14 December 2020 and 19 April 2021 in Ontario, Canada. Models were adjusted for age, sex, public health unit region, biweekly period of test, number of SARS-CoV-2 tests in the three months before 14 December 2020, presence of any comorbidity increasing the risk of severe covid-19, receipt of influenza vaccination in current or previous influenza season, and fifths of neighbourhood level household income, number of people in each dwelling, proportion of people employed as non-health essential workers, and self-identified visible minority

**Fig 4**
Adjusted vaccine effectiveness estimates ≥14 days after dose 1 (for those who received only one dose) and ≥0 days after dose 2 of covid-19 mRNA vaccines (BNT162b2, mRNA-1273) by various factors, including vaccine product, patient characteristics, epidemic wave, and SARS-CoV-2 lineage against laboratory confirmed symptomatic SARS-CoV-2 infection and severe outcomes (hospital admission or death) between 14 December 2020 and 19 April 2021 in Ontario, Canada. Models were adjusted for age, sex, public health unit region, biweekly period of test, number of SARS-CoV-2 tests in the three months before 14 December 2020, presence of any comorbidity increasing the risk of severe covid-19, receipt of influenza vaccination in current or previous influenza season, and fifths of neighbourhood level household income, number of people living in each dwelling, proportion of people employed as non-health essential workers, and self-identified visible minority (unless adjusted variable was used for stratification). *For vaccine effectiveness estimates against symptomatic SARS-CoV-2 infection, this interval was ≥7 days after dose 2. Against severe outcomes, vaccine effectiveness was evaluated for the entire period (≥0 days) after receipt of the second dose owing to the small number of outcomes. For subgroup analyses by characteristic and SARS-CoV-2 lineage, individuals vaccinated with either mRNA vaccine were included

**Fig 5**
Adjusted vaccine effectiveness estimates ≥14 days after dose 1 and ≥0 days after dose 2 of covid-19 mRNA vaccines (BNT162b2, mRNA-1273) against laboratory confirmed symptomatic SARS-CoV-2 infection and severe outcomes (hospital admission or death) by age group, between 14 December 2020 and 19 April 2021 in Ontario, Canada. Models were adjusted for age, sex, public health unit region, biweekly period of test, number of SARS-CoV-2 tests in the three months before 14 December 2020, presence of any comorbidity increasing the risk of severe covid-19, receipt of influenza vaccination in current or previous influenza season, and fifths of neighbourhood level household income, number of people living in each dwelling, proportion of people employed as non-health essential workers, and self-identified visible minority (unless adjusted variable was used for stratification). *For vaccine effectiveness estimates against symptomatic SARS-CoV-2 infection, this interval was ≥7 days after dose 2. Against severe outcomes, vaccine effectiveness was evaluated for the entire period (≥0 days) after receipt of the second dose owing to the small number of outcomes

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References

1. Patel MM, Jackson ML, Ferdinands J. Postlicensure Evaluation of COVID-19 Vaccines. JAMA 2020;324:1939-40. 10.1001/jama.2020.19328. - DOI - PubMed
1. National Advisory Committee on Immunization. COVID-19 vaccine: Guidance on the prioritization of initial doses - Canada.ca. 2021. https://www.canada.ca/en/public-health/services/immunization/national-advisory-c... (accessed 2 May 2021).
1. Jackson ML, Nelson JC. The test-negative design for estimating influenza vaccine effectiveness. Vaccine 2013;31:2165-8. 10.1016/j.vaccine.2013.02.053. - DOI - PubMed
1. Sullivan SG, Tchetgen Tchetgen EJ, Cowling BJ. Theoretical Basis of the Test-Negative Study Design for Assessment of Influenza Vaccine Effectiveness. Am J Epidemiol 2016;184:345-53. 10.1093/aje/kww064. - DOI - PMC - PubMed
1. Watson J, Whiting PF, Brush JE. Interpreting a covid-19 test result. BMJ 2020;369:m1808. 10.1136/bmj.m1808. - DOI - PubMed

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Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study

Affiliations

Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous