Protection of prior SARS-CoV-2 infection, COVID-19 boosters, and hybrid immunity against Omicron severe illness: A population-based cohort study of five million residents in Canada

PLoS One. 2024 Feb 23;19(2):e0299304. doi: 10.1371/journal.pone.0299304. eCollection 2024.

Abstract

Background: Evidence on protection of different patterns of infection- and vaccine-acquired immunity against Omicron-associated severe illness is useful in planning booster vaccination strategies. We examined protection of prior SARS-CoV-2 infection, a third or a fourth COVID-19 vaccine dose, and hybrid immunity against Omicron-associated severe illness.

Methods and findings: This population-based cohort study followed five million individuals with at least one SARS-CoV-2 RT-PCR test before November 21, 2021 until an Omicron-associatedhospitalization or death. We used Cox regression models to estimate risks of Omicron-associated hospitalization and a composite severe outcome (hospitalized and death), among individuals with infection- and/or vaccination-acquired immunity. Individuals who were unvaccinated and had no history of a prior infection severed as the reference group. Both adjusted hazard ratios (HR) and corresponding protection (one minus adjusted HR), with 95% confidence intervals (CIs), were reported. Three doses provided 94% (95%CI 93-95) and 93% (95%CI 91-94) protection against Omicron-associated hospitalization at 2-3 and ≥3 months post-vaccination respectively, similar to the protection conferred by three doses and a prior infection (2-3 months: 99%, 95%CI 97-100; ≥3 months: 97%, 95%CI 92-99) and four doses (1 month: 87%, 95%CI 79-92; 1-2 months: 96%, 95%CI 92-98). In individuals ≥65 years old, protection of four doses increased to 95% (95%CI 91-98) at 1-2 months, significantly higher than that of three doses over the follow-up period. Similar results were observed with the composite severe outcome.

Conclusion: At least three antigenic exposures, achieved by vaccination or infection, confers significant protection against Omicron-associated hospitalization and death in all age groups. Our findings support a third dose for the overall population, regardless of prior infection status, and a fourth dose for the elderly to maintain high level of immunity and substantially reduce risk of severe illness at individual level.

MeSH terms

  • Adaptive Immunity
  • Aged
  • COVID-19 Vaccines / therapeutic use
  • COVID-19* / prevention & control
  • Canada / epidemiology
  • Cohort Studies
  • Humans
  • SARS-CoV-2

Substances

  • COVID-19 Vaccines

Grants and funding

This study was supported by the Ontario Health Data Platform (OHDP), a Province of Ontario initiative to support Ontario’s ongoing response to COVID-19 and its related impacts. This analysis 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). We were not paid to write this manuscript by any pharmaceutical company or agency. SW is supported by the Dalla Lana School Implementation Science Interdisciplinary Cluster. XW is supported as the Dalla Lana Chair in Global Health Policy at the University of Toronto. XW declares funding from the Canadian Institutes of Health Research. JK is supported by a Clinician-Scientist award from the Department of Family and Community Medicine at the University of Toronto. SM is supported by a Tier 2 Canada Research Chair in Mathematical Modelling and Program Science. The funder was not involved in the study design, data collection, analysis, decision to publish, and preparation of the manuscript.