. 2023 May;23(5):556-567.

doi: 10.1016/S1473-3099(22)00801-5. Epub 2023 Jan 18.

Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: a systematic review and meta-regression

Niklas Bobrovitz¹, Harriet Ware², Xiaomeng Ma³, Zihan Li⁴, Reza Hosseini⁵, Christian Cao⁶, Anabel Selemon², Mairead Whelan², Zahra Premji⁷, Hanane Issa⁸, Brianna Cheng⁹, Laith J Abu Raddad¹⁰, David L Buckeridge¹¹, Maria D Van Kerkhove¹², Vanessa Piechotta¹³, Melissa M Higdon¹⁴, Annelies Wilder-Smith¹⁵, Isabel Bergeri¹², Daniel R Feikin¹⁶, Rahul K Arora¹⁷, Minal K Patel¹⁶, Lorenzo Subissi¹²

Affiliations

¹ Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada; Centre for Health Informatics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. Electronic address: niklas.bobrovitz@mail.utoronto.ca.
² Centre for Health Informatics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
³ Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁴ Centre for Health Informatics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Bioengineering, University of California, Berkeley, CA, USA.
⁵ Centre for Health Informatics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
⁶ Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Centre for Health Informatics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁷ Libraries, University of Victoria, Victoria, BC, Canada.
⁸ Institute of Health Informatics, University College London, London, UK.
⁹ Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁰ Infectious Disease Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar.
¹¹ Department of Epidemiology and Biostatistics, School of Population and Global Health, McGill University, Montreal, QC, Canada.
¹² Health Emergencies Programme, World Health Organization, Geneva, Switzerland.
¹³ Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
¹⁴ International Vaccine Access Center, Department of International Health, John Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
¹⁵ Department of Immunizations, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland; Heidelberg Institute of Global Health, University of Heidelberg, Germany.
¹⁶ Department of Immunizations, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland.
¹⁷ Centre for Health Informatics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Institute of Biomedical Engineering, University of Oxford, Oxford, UK.

PMID: 36681084
PMCID: PMC10014083
DOI: 10.1016/S1473-3099(22)00801-5

Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: a systematic review and meta-regression

Niklas Bobrovitz et al. Lancet Infect Dis. 2023 May.

. 2023 May;23(5):556-567.

doi: 10.1016/S1473-3099(22)00801-5. Epub 2023 Jan 18.

Authors

Affiliations

¹ Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada; Centre for Health Informatics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. Electronic address: niklas.bobrovitz@mail.utoronto.ca.
² Centre for Health Informatics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
³ Institute of Health Policy Management and Evaluation, University of Toronto, Toronto, ON, Canada.
⁴ Centre for Health Informatics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Bioengineering, University of California, Berkeley, CA, USA.
⁵ Centre for Health Informatics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
⁶ Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Centre for Health Informatics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁷ Libraries, University of Victoria, Victoria, BC, Canada.
⁸ Institute of Health Informatics, University College London, London, UK.
⁹ Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁰ Infectious Disease Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar.
¹¹ Department of Epidemiology and Biostatistics, School of Population and Global Health, McGill University, Montreal, QC, Canada.
¹² Health Emergencies Programme, World Health Organization, Geneva, Switzerland.
¹³ Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
¹⁴ International Vaccine Access Center, Department of International Health, John Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
¹⁵ Department of Immunizations, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland; Heidelberg Institute of Global Health, University of Heidelberg, Germany.
¹⁶ Department of Immunizations, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland.
¹⁷ Centre for Health Informatics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Institute of Biomedical Engineering, University of Oxford, Oxford, UK.

PMID: 36681084
PMCID: PMC10014083
DOI: 10.1016/S1473-3099(22)00801-5

Abstract

Background: The global surge in the omicron (B.1.1.529) variant has resulted in many individuals with hybrid immunity (immunity developed through a combination of SARS-CoV-2 infection and vaccination). We aimed to systematically review the magnitude and duration of the protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against infection and severe disease caused by the omicron variant.

Methods: For this systematic review and meta-regression, we searched for cohort, cross-sectional, and case-control studies in MEDLINE, Embase, Web of Science, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, the WHO COVID-19 database, and Europe PubMed Central from Jan 1, 2020, to June 1, 2022, using keywords related to SARS-CoV-2, reinfection, protective effectiveness, previous infection, presence of antibodies, and hybrid immunity. The main outcomes were the protective effectiveness against reinfection and against hospital admission or severe disease of hybrid immunity, hybrid immunity relative to previous infection alone, hybrid immunity relative to previous vaccination alone, and hybrid immunity relative to hybrid immunity with fewer vaccine doses. Risk of bias was assessed with the Risk of Bias In Non-Randomized Studies of Interventions Tool. We used log-odds random-effects meta-regression to estimate the magnitude of protection at 1-month intervals. This study was registered with PROSPERO (CRD42022318605).

Findings: 11 studies reporting the protective effectiveness of previous SARS-CoV-2 infection and 15 studies reporting the protective effectiveness of hybrid immunity were included. For previous infection, there were 97 estimates (27 with a moderate risk of bias and 70 with a serious risk of bias). The effectiveness of previous infection against hospital admission or severe disease was 74·6% (95% CI 63·1-83·5) at 12 months. The effectiveness of previous infection against reinfection waned to 24·7% (95% CI 16·4-35·5) at 12 months. For hybrid immunity, there were 153 estimates (78 with a moderate risk of bias and 75 with a serious risk of bias). The effectiveness of hybrid immunity against hospital admission or severe disease was 97·4% (95% CI 91·4-99·2) at 12 months with primary series vaccination and 95·3% (81·9-98·9) at 6 months with the first booster vaccination after the most recent infection or vaccination. Against reinfection, the effectiveness of hybrid immunity following primary series vaccination waned to 41·8% (95% CI 31·5-52·8) at 12 months, while the effectiveness of hybrid immunity following first booster vaccination waned to 46·5% (36·0-57·3) at 6 months.

Interpretation: All estimates of protection waned within months against reinfection but remained high and sustained for hospital admission or severe disease. Individuals with hybrid immunity had the highest magnitude and durability of protection, and as a result might be able to extend the period before booster vaccinations are needed compared to individuals who have never been infected.

Funding: WHO COVID-19 Solidarity Response Fund and the Coalition for Epidemic Preparedness Innovations.

© 2023 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests NB, HW, XM, ZL, RH, CC, AS, MW, BC, and RKA report grants unrelated to the present work from the WHO Health Emergencies Program, the Public Health Agency of Canada through Canada's COVID-19 Immunity Task Force (grant 2021-HQ-000056), the Robert Koch Institute, and the Canadian Medical Association Joule Innovation Fund. HI reports contracts unrelated to the present work from WHO. MMH reports contracts unrelated to the present work from WHO, Pfizer, and the Bill & Melinda Gates Foundation. VP is an unpaid governing board member and Royal Trustee at Cochrane. RKA reports consulting fees unrelated to the present work from the Bill & Melinda Gates Foundation Strategic Investment Fund, Health Canada, and Flagship Pioneering, and stock in Alethea Medical that is unrelated to the present work. MDVK, IB, DF, and LS are employed by WHO. MMH has contracts with WHO, CEPI, and the Asian Development Bank to gather data on COVID-19 vaccine efficacy, effectiveness, and safety from published studies, and reports unrelated grants from Pfizer and the Bill & Melinda Gates Foundation. AW-S and MKP consult on COVID-19 research and policy for WHO.

Figures

**Figure 1**
Study selection *There were two rounds of full-text screening. Studies not meeting general inclusion criteria were excluded in the first round. In the second round, articles were screened with criteria specific to the types of exposures and comparators being reported (ie, previous infection and hybrid immunity). †There were 16 unique articles: nine articles reported on one study, five articles reported on two studies (one on previous infection and one on hybrid immunity), one article reported on three studies (one on previous infection and two on hybrid immunity), and one article reported on four studies (two on previous infection and two on hybrid immunity). Seven articles reported data for previous infection and hybrid immunity.

**Figure 2**
Protection against omicron variant conferred by previous infection or hybrid immunity compared to immune-naive individuals over time This analysis uses a log-odds meta-regression model. Points of the same color represent estimates from the same study. The diameter of the circles varies with the sample size of the study. Dotted lines represent 95% CIs. Solid black lines represent point estimates.

**Figure 3**
Protection against omicron variant conferred by the primary series vaccine, first booster vaccine, previous infection, and hybrid immunity compared to immune-naive individuals over time The shaded areas denote 95% CIs. Vaccine effectiveness data were procured from a separate systematic review.

See this image and copyright information in PMC

Comment in

The benefit of vaccination after previous SARS-CoV-2 infection in the omicron era.
Boaventura VS, Cerqueira-Silva T, Barral-Netto M. Boaventura VS, et al. Lancet Infect Dis. 2023 May;23(5):511-512. doi: 10.1016/S1473-3099(22)00880-5. Epub 2023 Jan 18. Lancet Infect Dis. 2023. PMID: 36681085 Free PMC article. No abstract available.
Risk of omicron infection for high-risk older adults in long-term care facilities.
Pallett SJC, Heskin J, Keating F, Mazzella A, O'Shea MK, Moore LSP. Pallett SJC, et al. Lancet Infect Dis. 2023 May;23(5):526-527. doi: 10.1016/S1473-3099(23)00179-2. Epub 2023 Mar 17. Lancet Infect Dis. 2023. PMID: 36940702 Free PMC article. No abstract available.

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Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: a systematic review and meta-regression

Affiliations

Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: a systematic review and meta-regression

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Conflict of interest statement

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