Immune histories and natural infection protection during the omicron era

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

doi:10.1038/s43856-025-00974-9

Immune histories and natural infection protection during the omicron era

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^*

^*Corresponding author for this work

Weill Cornell Medicine-Qatar
Cornell University
Qatar University
University of Calgary
Hamad Medical Corporation
Queen's University Belfast
University of British Columbia
McMaster University
Primary Health Corporation (PHCC)
Ministry of Public Health Qatar
HBKU College of Health and Life Sciences

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

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.

Original language	English
Article number	262
Number of pages	10
Journal	Communications Medicine
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s43856-025-00974-9
Publication status	Published - Dec 2025
Externally published	Yes

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10.1038/s43856-025-00974-9

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Chemaitelly, H., Ayoub, H. H., Bobrovitz, N., Coyle, P., Tang, P., Hasan, M. R., Yassine, H. M., Al Thani, A. A., Al-Kanaani, Z., Al-Kuwari, E., Jeremijenko, A., Kaleeckal, A. H., Latif, A. N., Shaik, R. M., Abdul-Rahim, H. F., Nasrallah, G. K., Al-Kuwari, M. G., Al-Romaihi, H. E., Al-Thani, M. H., ... Abu-Raddad, L. J. (2025). Immune histories and natural infection protection during the omicron era. Communications Medicine, 5(1), Article 262. https://doi.org/10.1038/s43856-025-00974-9

@article{92a92cfb162443f3bd0bc86dcb0e4759,

title = "Immune histories and natural infection protection during the omicron era",

abstract = "Background: Past immunological events can either enhance or compromise an individual{\textquoteright}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{\textendash}1.43); 0.93 (95\% CI: 0.68{\textendash}1.28) for the unvaccinated and 1.34 (95\% CI: 1.18{\textendash}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{\textendash}1.65); 1.12 (95\% CI: 0.63{\textendash}1.97) for the unvaccinated and 1.42 (95\% CI: 1.16{\textendash}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{\textendash}1.03); 0.75 (95\% CI: 0.66{\textendash}0.85) for the unvaccinated and 1.03 (95\% CI: 0.97{\textendash}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.",

author = "Hiam Chemaitelly and Ayoub, \{Houssein H.\} and Niklas Bobrovitz and Peter Coyle and Patrick Tang and Hasan, \{Mohammad R.\} and Yassine, \{Hadi M.\} and \{Al Thani\}, \{Asmaa A.\} and Zaina Al-Kanaani and Einas Al-Kuwari and Andrew Jeremijenko and Kaleeckal, \{Anvar Hassan\} and Latif, \{Ali Nizar\} and Shaik, \{Riyazuddin Mohammad\} and Abdul-Rahim, \{Hanan F.\} and Nasrallah, \{Gheyath K.\} and Al-Kuwari, \{Mohamed Ghaith\} and Al-Romaihi, \{Hamad Eid\} and Al-Thani, \{Mohamed H.\} and Abdullatif Al-Khal and Roberto Bertollini and Butt, \{Adeel A.\} and Abu-Raddad, \{Laith J.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

doi = "10.1038/s43856-025-00974-9",

language = "English",

volume = "5",

journal = "Communications Medicine",

issn = "2730-664X",

publisher = "Springer Nature",

number = "1",

}

Chemaitelly, H, Ayoub, HH, Bobrovitz, N, Coyle, P, Tang, P, Hasan, MR, Yassine, HM, Al Thani, AA, Al-Kanaani, Z, Al-Kuwari, E, Jeremijenko, A, Kaleeckal, AH, Latif, AN, Shaik, RM, Abdul-Rahim, HF, Nasrallah, GK, Al-Kuwari, MG, Al-Romaihi, HE, Al-Thani, MH, Al-Khal, A, Bertollini, R, Butt, AA & Abu-Raddad, LJ 2025, 'Immune histories and natural infection protection during the omicron era', Communications Medicine, vol. 5, no. 1, 262. https://doi.org/10.1038/s43856-025-00974-9

TY - JOUR

T1 - Immune histories and natural infection protection during the omicron era

AU - Chemaitelly, Hiam

AU - Ayoub, Houssein H.

AU - Bobrovitz, Niklas

AU - Coyle, Peter

AU - Tang, Patrick

AU - Hasan, Mohammad R.

AU - Yassine, Hadi M.

AU - Al Thani, Asmaa A.

AU - Al-Kanaani, Zaina

AU - Al-Kuwari, Einas

AU - Jeremijenko, Andrew

AU - Kaleeckal, Anvar Hassan

AU - Latif, Ali Nizar

AU - Shaik, Riyazuddin Mohammad

AU - Abdul-Rahim, Hanan F.

AU - Nasrallah, Gheyath K.

AU - Al-Kuwari, Mohamed Ghaith

AU - Al-Romaihi, Hamad Eid

AU - Al-Thani, Mohamed H.

AU - Al-Khal, Abdullatif

AU - Bertollini, Roberto

AU - Butt, Adeel A.

AU - Abu-Raddad, Laith J.

PY - 2025/12

Y1 - 2025/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105009714898

U2 - 10.1038/s43856-025-00974-9

DO - 10.1038/s43856-025-00974-9

M3 - Article

AN - SCOPUS:105009714898

SN - 2730-664X

VL - 5

JO - Communications Medicine

JF - Communications Medicine

IS - 1

M1 - 262

ER -

Immune histories and natural infection protection during the omicron era

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