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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

BMJ 2021; 374 doi: (Published 20 August 2021) Cite this as: BMJ 2021;374:n1943

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  1. Hannah Chung, associate research methodologist1,
  2. Siyi He, research analyst1,
  3. Sharifa Nasreen, postdoctoral fellow1,
  4. Maria E Sundaram, postdoctoral fellow12,
  5. Sarah A Buchan, scientist and assistant professor1234,
  6. Sarah E Wilson, medical epidemiologist and assistant professor1234,
  7. Branson Chen, senior health information analyst1,
  8. Andrew Calzavara, associate research methodologist1,
  9. Deshayne B Fell, scientist and associate professor156,
  10. Peter C Austin, senior scientist and professor17,
  11. Kumanan Wilson, senior scientist and professor589,
  12. Kevin L Schwartz, infection prevention and control physician and assistant professor123,
  13. Kevin A Brown, scientist and assistant professor123,
  14. Jonathan B Gubbay, medical microbiologist and associate professor310,
  15. Nicole E Basta, associate professor11,
  16. Salaheddin M Mahmud, director and professor12,
  17. Christiaan H Righolt, analytics manager12,
  18. Lawrence W Svenson, provincial health analytics officer and associate professor13141516,
  19. Shannon E MacDonald, associate professor1517,
  20. Naveed Z Janjua, senior scientist and clinical professor1819,
  21. Mina Tadrous, scientist and assistant professor12021,
  22. Jeffrey C Kwong, senior scientist and professor12342223
  23. on behalf of the Canadian Immunization Research Network (CIRN) Provincial Collaborative Network (PCN) Investigators
  1. 1ICES, Toronto, ON, Canada
  2. 2Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
  3. 3Public Health Ontario, ON, Canada
  4. 4Centre for Vaccine Preventable Diseases, University of Toronto, Toronto, ON, Canada
  5. 5School of Epidemiology and Public Health, University of Ottawa, ON, Canada
  6. 6Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada
  7. 7Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada
  8. 8Bruyère and Ottawa Hospital Research Institutes, Ottawa, ON, Canada
  9. 9Department of Medicine, University of Ottawa, Ottawa, ON, Canada
  10. 10Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
  11. 11Department of Epidemiology, Biostatistics, and Occupational Health, School of Population and Global Health, McGill University, Montreal, QC, Canada
  12. 12Vaccine and Drug Evaluation Centre, Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada
  13. 13Analytics and Performance Reporting Branch, Alberta Health, Edmonton, AB, Canada
  14. 14Division of Preventive Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
  15. 15School of Public Health, University of Alberta, Edmonton, AB, Canada
  16. 16Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
  17. 17Faculty of Nursing, University of Alberta, Edmonton, AB, Canada
  18. 18British Columbia Centre for Disease Control, Vancouver, BC, Canada
  19. 19School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
  20. 20Women’s College Hospital, Toronto, ON, Canada
  21. 21Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
  22. 22Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada
  23. 23University Health Network, Toronto, ON, Canada
  1. Correspondence to: J Kwong jeff.kwong{at} (or @DrJeffKwong on Twitter)
  • Accepted 2 August 2021


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.


  • Contributors: HC and JCK designed and oversaw the study. SH and HC obtained the data and conducted all analyses (dataset and variable creation and statistical modelling). BC contributed to data analyses and data preparation for the symptomatic dataset. SN, MES, HC, and JCK drafted the manuscript. All authors contributed to the analysis plan, interpreted the results, critically reviewed and edited the manuscript, approved the final version, and agreed to be accountable for all aspects of the work. JCK is the guarantor. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: This work was supported by the Canadian Immunization Research Network (CIRN) through a grant from the Public Health Agency of Canada and the Canadian Institutes of Health Research (CNF 151944); funding from the Public Health Agency of Canada, through the Vaccine Surveillance Reference group and the COVID-19 Immunity Task Force; and ICES, which is funded by an annual grant from Ontario’s Ministry of Health (MOH) and Ministry of Long term Care (MLTC); and the Ontario Health Data Platform (OHDP), a Province of Ontario initiative to support Ontario’s ongoing response to covid-19 and its related impacts. JCK is supported by a clinician-scientist award from the University of Toronto Department of Family and Community Medicine. PCA is supported by a mid-career investigator award from the Heart and Stroke Foundation. The study sponsors did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

  • Parts of this material are based on data and/or information compiled and provided by the Canadian Institute for Health Information (CIHI) and by Cancer Care Ontario (CCO). However, the analyses, conclusions, opinions, and statement expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement by ICES, MOH, MLTC, OHDP, its partners, the Province of Ontario, CIHI, or CCO is intended or should be inferred.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at 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.

  • The corresponding author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

  • Dissemination to participants and related patient and public communities: As the personal identifying information of participants have been removed from the study dataset, it is not possible to send the results of this study to participants. However, the results from this manuscript have been made publicly available through a preprint server and will be further disseminated by ICES through social media channels and news media.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

Data availability statement

The study dataset is held securely in coded form at ICES. While legal data sharing agreements between ICES and data providers (eg, healthcare organisations and government) prohibit ICES from making the dataset publicly available, access might be granted to those who meet prespecified criteria for confidential access, available at (email The full dataset creation plan and underlying analytic code are available from the authors upon request, understanding that the computer programs might rely upon coding templates or macros that are unique to ICES and are therefore either inaccessible or require modification.

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See:

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