Immune histories and natural infection protection during the omicron era

Abstract Background Past immunological events can either enhance or compromise an individual’s future immune protection. This study investigated how different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) natural infection histories before an omicron infection, with or without vaccina...

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Main Authors: Hiam Chemaitelly, Houssein H. Ayoub, Niklas Bobrovitz, Peter Coyle, Patrick Tang, Mohammad R. Hasan, Hadi M. Yassine, Asmaa A. Al Thani, Zaina Al-Kanaani, Einas Al-Kuwari, Andrew Jeremijenko, Anvar Hassan Kaleeckal, Ali Nizar Latif, Riyazuddin Mohammad Shaik, Hanan F. Abdul-Rahim, Gheyath K. Nasrallah, Mohamed Ghaith Al-Kuwari, Hamad Eid Al-Romaihi, Mohamed H. Al-Thani, Abdullatif Al-Khal, Roberto Bertollini, Adeel A. Butt, Laith J. Abu-Raddad
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Communications Medicine
Online Access:https://doi.org/10.1038/s43856-025-00974-9
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author Hiam Chemaitelly
Houssein H. Ayoub
Niklas Bobrovitz
Peter Coyle
Patrick Tang
Mohammad R. Hasan
Hadi M. Yassine
Asmaa A. Al Thani
Zaina Al-Kanaani
Einas Al-Kuwari
Andrew Jeremijenko
Anvar Hassan Kaleeckal
Ali Nizar Latif
Riyazuddin Mohammad Shaik
Hanan F. Abdul-Rahim
Gheyath K. Nasrallah
Mohamed Ghaith Al-Kuwari
Hamad Eid Al-Romaihi
Mohamed H. Al-Thani
Abdullatif Al-Khal
Roberto Bertollini
Adeel A. Butt
Laith J. Abu-Raddad
author_facet Hiam Chemaitelly
Houssein H. Ayoub
Niklas Bobrovitz
Peter Coyle
Patrick Tang
Mohammad R. Hasan
Hadi M. Yassine
Asmaa A. Al Thani
Zaina Al-Kanaani
Einas Al-Kuwari
Andrew Jeremijenko
Anvar Hassan Kaleeckal
Ali Nizar Latif
Riyazuddin Mohammad Shaik
Hanan F. Abdul-Rahim
Gheyath K. Nasrallah
Mohamed Ghaith Al-Kuwari
Hamad Eid Al-Romaihi
Mohamed H. Al-Thani
Abdullatif Al-Khal
Roberto Bertollini
Adeel A. Butt
Laith J. Abu-Raddad
author_sort Hiam Chemaitelly
collection DOAJ
description Abstract Background Past immunological events can either enhance or compromise an individual’s future immune protection. This study investigated how different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) natural infection histories before an omicron infection, with or without vaccination, influence protection against subsequent omicron reinfection. Methods Three national, matched, retrospective cohort studies were conducted in Qatar from February 28, 2020, to August 12, 2024 to compare incidence of omicron reinfection between individuals with two omicron infections (omicron double-infection cohort) and those with one (omicron single-infection cohort); the omicron double-infection cohort with individuals who had a pre-omicron infection followed by an omicron reinfection (pre-omicron-omicron double-infection cohort); and the pre-omicron-omicron double-infection cohort with the omicron single-infection cohort. Results Here we show that, in the first study, comparing the omicron double-infection cohort to the omicron single-infection cohort, the adjusted hazard ratio (aHR) is 1.27 (95% CI: 1.13–1.43); 0.93 (95% CI: 0.68–1.28) for the unvaccinated and 1.34 (95% CI: 1.18–1.52) for the vaccinated. In the second study, comparing the omicron double-infection cohort to the pre-omicron-omicron double-infection cohort, the aHR is 1.37 (95% CI: 1.13–1.65); 1.12 (95% CI: 0.63–1.97) for the unvaccinated and 1.42 (95% CI: 1.16–1.74) for the vaccinated. In the third study, comparing the pre-omicron-omicron double-infection cohort to the omicron single-infection cohort, the aHR is 0.97 (95% CI: 0.92–1.03); 0.75 (95% CI: 0.66–0.85) for the unvaccinated and 1.03 (95% CI: 0.97–1.09) for the vaccinated. Conclusions Immune history shapes protection against omicron reinfection, with pre-omicron-omicron immunity enhancing protection, while repeated similar exposures reduce protection against new variants.
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spelling doaj-art-d46f6abcfdff411087339f3ceb7da49d2025-08-20T03:45:31ZengNature PortfolioCommunications Medicine2730-664X2025-07-015111010.1038/s43856-025-00974-9Immune histories and natural infection protection during the omicron eraHiam Chemaitelly0Houssein H. Ayoub1Niklas Bobrovitz2Peter Coyle3Patrick Tang4Mohammad R. Hasan5Hadi M. Yassine6Asmaa A. Al Thani7Zaina Al-Kanaani8Einas Al-Kuwari9Andrew Jeremijenko10Anvar Hassan Kaleeckal11Ali Nizar Latif12Riyazuddin Mohammad Shaik13Hanan F. Abdul-Rahim14Gheyath K. Nasrallah15Mohamed Ghaith Al-Kuwari16Hamad Eid Al-Romaihi17Mohamed H. Al-Thani18Abdullatif Al-Khal19Roberto Bertollini20Adeel A. Butt21Laith J. Abu-Raddad22Infectious Disease Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell UniversityMathematics Program, Department of Mathematics and Statistics, College of Arts and Sciences, Qatar UniversityDepartment of Emergency Medicine, Cumming School of Medicine, University of CalgaryHamad Medical CorporationDepartment of Pathology and Laboratory Medicine, University of British ColumbiaDepartment of Pathology and Molecular Medicine, McMaster UniversityDepartment of Biomedical Science, College of Health Sciences, QU Health, Qatar UniversityDepartment of Biomedical Science, College of Health Sciences, QU Health, Qatar UniversityHamad Medical CorporationHamad Medical CorporationHamad Medical CorporationHamad Medical CorporationHamad Medical CorporationHamad Medical CorporationDepartment of Public Health, College of Health Sciences, QU Health, Qatar UniversityDepartment of Biomedical Science, College of Health Sciences, QU Health, Qatar UniversityPrimary Health Care CorporationMinistry of Public HealthMinistry of Public HealthHamad Medical CorporationMinistry of Public HealthDepartment of Population Health Sciences, Weill Cornell Medicine, Cornell UniversityInfectious Disease Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell UniversityAbstract Background Past immunological events can either enhance or compromise an individual’s future immune protection. This study investigated how different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) natural infection histories before an omicron infection, with or without vaccination, influence protection against subsequent omicron reinfection. Methods Three national, matched, retrospective cohort studies were conducted in Qatar from February 28, 2020, to August 12, 2024 to compare incidence of omicron reinfection between individuals with two omicron infections (omicron double-infection cohort) and those with one (omicron single-infection cohort); the omicron double-infection cohort with individuals who had a pre-omicron infection followed by an omicron reinfection (pre-omicron-omicron double-infection cohort); and the pre-omicron-omicron double-infection cohort with the omicron single-infection cohort. Results Here we show that, in the first study, comparing the omicron double-infection cohort to the omicron single-infection cohort, the adjusted hazard ratio (aHR) is 1.27 (95% CI: 1.13–1.43); 0.93 (95% CI: 0.68–1.28) for the unvaccinated and 1.34 (95% CI: 1.18–1.52) for the vaccinated. In the second study, comparing the omicron double-infection cohort to the pre-omicron-omicron double-infection cohort, the aHR is 1.37 (95% CI: 1.13–1.65); 1.12 (95% CI: 0.63–1.97) for the unvaccinated and 1.42 (95% CI: 1.16–1.74) for the vaccinated. In the third study, comparing the pre-omicron-omicron double-infection cohort to the omicron single-infection cohort, the aHR is 0.97 (95% CI: 0.92–1.03); 0.75 (95% CI: 0.66–0.85) for the unvaccinated and 1.03 (95% CI: 0.97–1.09) for the vaccinated. Conclusions Immune history shapes protection against omicron reinfection, with pre-omicron-omicron immunity enhancing protection, while repeated similar exposures reduce protection against new variants.https://doi.org/10.1038/s43856-025-00974-9
spellingShingle Hiam Chemaitelly
Houssein H. Ayoub
Niklas Bobrovitz
Peter Coyle
Patrick Tang
Mohammad R. Hasan
Hadi M. Yassine
Asmaa A. Al Thani
Zaina Al-Kanaani
Einas Al-Kuwari
Andrew Jeremijenko
Anvar Hassan Kaleeckal
Ali Nizar Latif
Riyazuddin Mohammad Shaik
Hanan F. Abdul-Rahim
Gheyath K. Nasrallah
Mohamed Ghaith Al-Kuwari
Hamad Eid Al-Romaihi
Mohamed H. Al-Thani
Abdullatif Al-Khal
Roberto Bertollini
Adeel A. Butt
Laith J. Abu-Raddad
Immune histories and natural infection protection during the omicron era
Communications Medicine
title Immune histories and natural infection protection during the omicron era
title_full Immune histories and natural infection protection during the omicron era
title_fullStr Immune histories and natural infection protection during the omicron era
title_full_unstemmed Immune histories and natural infection protection during the omicron era
title_short Immune histories and natural infection protection during the omicron era
title_sort immune histories and natural infection protection during the omicron era
url https://doi.org/10.1038/s43856-025-00974-9
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