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. 2024 May 15;78(5):1372-1382.
doi: 10.1093/cid/ciad716.

Protection Conferred by COVID-19 Vaccination, Prior SARS-CoV-2 Infection, or Hybrid Immunity Against Omicron-Associated Severe Outcomes Among Community-Dwelling Adults

Nelson Lee  1 , Lena Nguyen  2 , Peter C Austin  2   3 , Kevin A Brown  1   2   4 , Ramandip Grewal  1   2   4   5 , Sarah A Buchan  1   2   3   4   5 , Sharifa Nasreen  1   2 , Jonathan Gubbay  6 , Kevin L Schwartz  1   2   4 , Mina Tadrous  2   7   8 , Kumanan Wilson  9   10   11 , Sarah E Wilson  1   2   4   5 , Jeffrey C Kwong  1   2   4   5   12   13
Affiliations

Protection Conferred by COVID-19 Vaccination, Prior SARS-CoV-2 Infection, or Hybrid Immunity Against Omicron-Associated Severe Outcomes Among Community-Dwelling Adults

Nelson Lee et al. Clin Infect Dis. .

Abstract

Introduction: We assessed protection from coronavirus disease 2019 (COVID-19) vaccines and/or prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection against Omicron-associated severe outcomes during successive sublineage-predominant periods.

Methods: We used a test-negative design to estimate protection by vaccines and/or prior infection against hospitalization/death among community-dwelling, polymerase chain reaction (PCR)-tested adults aged ≥50 years in Ontario, Canada, between 2 January 2022 and 30 June 2023. Multivariable logistic regression was used to estimate the relative change in the odds of hospitalization/death with each vaccine dose (2-5) and/or prior PCR-confirmed SARS-CoV-2 infection (compared with unvaccinated, uninfected subjects) up to 15 months since the last vaccination or infection.

Results: We included 18 526 cases with Omicron-associated severe outcomes and 90 778 test-negative controls. Vaccine protection was high during BA.1/BA.2 predominance but was generally <50% during periods of BA.4/BA.5 and BQ/XBB predominance without boosters. A third/fourth dose transiently increased protection during BA.4/BA.5 predominance (third-dose, 6-month: 68%, 95% confidence interval [CI] 63%-72%; fourth-dose, 6-month: 80%, 95% CI 77%-83%) but was lower and waned quickly during BQ/XBB predominance (third-dose, 6-month: 59%, 95% CI 48%-67%; 12-month: 49%, 95% CI 41%-56%; fourth-dose, 6-month: 62%, 95% CI 56%-68%, 12-months: 51%, 95% CI 41%-56%). Hybrid immunity conferred nearly 90% protection throughout BA.1/BA.2 and BA.4/BA.5 predominance but was reduced during BQ/XBB predominance (third-dose, 6-month: 60%, 95% CI 36%-75%; fourth-dose, 6-month: 63%, 95% CI 42%-76%). Protection was restored with a fifth dose (bivalent; 6-month: 91%, 95% CI 79%-96%). Prior infection alone did not confer lasting protection.

Conclusions: Protection from COVID-19 vaccines and/or prior SARS-CoV-2 infections against severe outcomes is reduced when immune-evasive variants/subvariants emerge and may also wane over time. Our findings support a variant-adapted booster vaccination strategy with periodic review.

Keywords: COVID-19 vaccination; Omicron; adults; hybrid immunity; severe outcomes.

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Conflict of interest statement

Potential conflicts of interest. N. L. has previously received honoraria for consultancy work, speaking in educational programs, and/or travel support from: Shionogi Inc., Gilead Sciences Canada Inc., Janssen Inc., GlaxoSmithKline plc., Sanofi Pasteur Ltd., F. Hoffmann-La Roche Ltd., Genentech Inc., CIDARA Therapeutics Inc., Clarion Healthcare, bioStrategies, Technospert, Aligos; all unrelated to this work. K. W. is a shareholder and board member and Co-founder and Chief Scientific Officer of CANImmunize Inc. and has served on independent scientific advisory boards for Medicago (Independent Data Monitoring Committee) and Moderna (Global Advisory Core Consultancy Group). J. G. reports a position as a paid consultant scientific editor for GIDEON Informatics, Inc., which is unrelated to the current work. S. E. W. reports being a co-investigator on a grant related to public health surveillance of invasive pneumococcal disease (no involvement in administration of funds) for the Canadian Immunization Research Network and a co-investigator on a grant on immunization data in Canada (no involvement in administration of funds) for CIRN; travel support to attend the Future of Vaccinology conference in October 2023 as an invited speaker from McMaster University (Hamilton, ON) and a role as an unpaid volunteer member for Canada's National Advisory Committee on Immunization (NACI). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Percentage of COVID-19 cases by the most prevalent Omicron sublineages and week in Ontario, 2 January 2022 to 30 June 2023. Abbreviation: COVID-19, coronavirus disease 2019.
Figure 2.
Figure 2.
Estimated protection (proportionate reduction) conferred by mRNA COVID-19 vaccines and/or prior SARS-CoV-2 infections against severe outcomes, by time since the last immunogenic event, according to documented prior infection status. Results are reported for each sublineage (BA.1/BA.2, BA.4/BA.5, BQ/XBB) predominant period. Note: “unvaccinated”—subjects who never received COVID-19 vaccine; “second dose”—subjects who received a second dose as the last dose of vaccine; “third dose”—subjects who received a third dose as the last dose of vaccine; same for “fourth dose” and “fifth dose.” “Time since the last immunogenic event”—at 3, 6, 9, 12, and 15 m since last vaccination or prior infection, whichever occurred later. Results not reported if insufficient data or unstable estimate (95% CI width exceeded 150 percentage points). Abbreviations: CI, confidence interval; COVID-19, coronavirus disease 2019; mRNA, messenger RNA; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Figure 3.
Figure 3.
Estimated marginal protection conferred by hybrid immunity (vaccination and documented prior SARS-CoV-2 infection vs vaccination alone) against severe outcomes, by time since the last immunogenic event, according to the number of COVID-19 vaccine doses received. Results are reported for each sublineage (BA.1/BA.2, BA.4/BA.5, BQ/XBB) predominant period. Abbreviations: COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
Figure 4.
Figure 4.
Estimated marginal protection conferred by booster doses against severe outcomes, using those who were last vaccinated >12 m ago as the reference group, by time since the last COVID-19 vaccine dose, according to the number of doses received. Results are reported for each sublineage (BA.1/BA.2, BA.4/BA.5, BQ/XBB) predominant period. Abbreviation: COVID-19, coronavirus disease 2019.
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