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Estimated Effectiveness of COVID-19 Vaccines Against Omicron or Delta Symptomatic Infection and Severe Outcomes

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Question  What is the estimated effectiveness of COVID-19 vaccines for preventing symptomatic infections due to the Omicron and Delta variants and severe outcomes (hospitalization or death) associated with these infections?

Findings  In this test-negative case-control study of 134 435 adults in Ontario, Canada, the estimated effectiveness of 2 doses of COVID-19 vaccine was high against symptomatic Delta infection and severe outcomes and was lower against symptomatic Omicron infection. After a third dose, estimated vaccine effectiveness against Omicron was 61% for symptomatic infection and 95% for severe outcomes.

Meaning  The findings suggest that 3 doses of COVID-19 vaccine may protect against symptomatic Omicron infection and severe outcomes, but other measures are also likely needed to prevent Omicron infection.

Abstract

Importance  The incidence of SARS-CoV-2 infection, including among individuals who have received 2 doses of COVID-19 vaccine, increased substantially following the emergence of the Omicron variant in Ontario, Canada. Understanding the estimated effectiveness of 2 or 3 doses of COVID-19 vaccine against outcomes associated with Omicron and Delta infections may aid decision-making at the individual and population levels.

Objective  To estimate vaccine effectiveness (VE) against symptomatic infections due to the Omicron and Delta variants and severe outcomes (hospitalization or death) associated with these infections.

Design, Setting, and Participants  This test-negative case-control study used linked provincial databases for SARS-CoV-2 laboratory testing, reportable disease, COVID-19 vaccination, and health administration in Ontario, Canada. Participants were individuals aged 18 years or older who had COVID-19 symptoms or severe outcomes (hospitalization or death) and were tested for SARS-CoV-2 between December 6 and 26, 2021.

Exposures  Receipt of 2 or 3 doses of the COVID-19 vaccine and time since last dose.

Main Outcomes and Measures  The main outcomes were symptomatic Omicron or Delta infection and severe outcomes (hospitalization or death) associated with infection. Multivariable logistic regression was used to estimate the effectiveness of 2 or 3 COVID-19 vaccine doses by time since the latest dose compared with no vaccination. Estimated VE was calculated using the formula VE = (1 – [adjusted odds ratio]) × 100%.

Results  Of 134 435 total participants, 16 087 were Omicron-positive cases (mean [SD] age, 36.0 [14.1] years; 8249 [51.3%] female), 4261 were Delta-positive cases (mean [SD] age, 44.2 [16.8] years; 2199 [51.6%] female), and 114 087 were test-negative controls (mean [SD] age, 42.0 [16.5] years; 67 884 [59.5%] female). Estimated VE against symptomatic Delta infection decreased from 89% (95% CI, 86%-92%) 7 to 59 days after a second dose to 80% (95% CI, 74%-84%) after 240 or more days but increased to 97% (95% CI, 96%-98%) 7 or more days after a third dose. Estimated VE against symptomatic Omicron infection was 36% (95% CI, 24%-45%) 7 to 59 days after a second dose and 1% (95% CI, –8% to 10%) after 180 days or longer, but 7 or more days after a third dose, it increased to 61% (95% CI, 56%-65%). Estimated VE against severe outcomes was high 7 or more days after a third dose for both Delta (99%; 95% CI, 98%-99%) and Omicron (95%; 95% CI, 87%-98%).

Conclusions and Relevance  In this study, in contrast to high estimated VE against symptomatic Delta infection and severe outcomes after 2 doses of COVID-19 vaccine, estimated VE was modest and short term against symptomatic Omicron infection but better maintained against severe outcomes. A third dose was associated with improved estimated VE against symptomatic infection and with high estimated VE against severe outcomes for both variants. Preventing infection due to Omicron and potential future variants may require tools beyond the currently available vaccines.

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Article Information

Accepted for Publication: July 19, 2022.

Published: September 22, 2022. doi:10.1001/jamanetworkopen.2022.32760

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Buchan SA et al. JAMA Network Open.

Corresponding Author: Jeffrey C. Kwong, MD, ICES, G1 06, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada (jeff.kwong@utoronto.ca).

Author Contributions: Ms Chung and Dr Kwong had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Buchan, Chung, Brown, Fell, Schwartz, Kwong.

Acquisition, analysis, or interpretation of data: Buchan, Chung, Austin, Fell, Gubbay, Nasreen, Schwartz, Sundaram, Tadrous, K. Wilson, S.E. Wilson, Kwong.

Drafting of the manuscript: Buchan, Chung, Kwong.

Critical revision of the manuscript for important intellectual content: Chung, Brown, Austin, Fell, Gubbay, Nasreen, Schwartz, Sundaram, Tadrous, K. Wilson, S.E. Wilson, Kwong.

Statistical analysis: Chung, Brown.

Obtained funding: Fell, Kwong.

Administrative, technical, or material support: Buchan, Schwartz, Sundaram.

Supervision: Brown, Kwong.

Conflict of Interest Disclosures: Dr Buchan reported receiving grants from the Canadian Institutes of Health Research and the Public Health Agency of Canada during the conduct of the study. Dr Austin reported being supported by a Mid-Career Investigator Award from the Heart and Stroke Foundation. Dr Gubbay reported being a consultant scientific editor for the Global Infectious Diseases Epidemiology Online Network. Dr Sundaram reported receiving grants from GSK outside the submitted work. Dr K. Wilson reported being the chief executive officer and cofounder of CANImmunize Inc, being a member of the independent data monitoring committee of Medicago, and serving on the data safety board for the Medicago COVID-19 vaccine trial outside the submitted work. Dr S. E. Wilson reported receiving grants from the Public Health Agency of Canada COVID-19 Immunity Task Force and the Canadian Immunization Research Network during the conduct of the study. Dr Kwong reported receiving grants from the Public Health Agency of Canada and the Canadian Institutes of Health Research during the conduct of the study and being supported by a Clinician-Scientist Award from the University of Toronto Department of Family and Community Medicine. No other disclosures were reported.

Funding/Support: This work was supported by the Canadian Immunization Research Network (CIRN) through grant CNF 151944 from the Public Health Agency of Canada and the Canadian Institutes of Health Research and CITF-VSRG-01 from the Public Health Agency of Canada through the Vaccine Surveillance Reference Group and the COVID-19 Immunity Task Force. This study was also supported by ICES (which is funded by an annual grant from the Ontario Ministry of Health [MOH] and the Ministry of Long-Term Care [MLTC]), Public Health Ontario, 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. Parts of this study were based on data and/or information compiled and provided by the Canadian Institute for Health Information (CIHI) and by Ontario Health (OH).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources. No endorsement by ICES, the MOH, the MLTC, the OHDP, or their partners; the Province of Ontario; the CIHI; or OH is intended or should be inferred.

Additional Contributions: Public Health Ontario provided access to vaccination data from COVaxON, case-level data from the Public Health Case and Contact Management System (CCM), and COVID-19 laboratory data as well as assistance with data interpretation. The staff of Ontario’s public health units were responsible for COVID-19 case and contact management and data collection within the CCM. IQVIA Solutions Canada Inc permitted use of its Drug Information File. The CIRN provided networking support. We thank the Ontario residents, without whom this research would be impossible.

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