Differential protection against SARS-CoV-2 reinfection pre- and post-Omicron

Hiam Chemaitelly (), Houssein H. Ayoub, 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, Adeel A. Butt, Hamad Eid Al-Romaihi, Mohamed H. Al-Thani, Abdullatif Al-Khal, Roberto Bertollini and Laith J. Abu-Raddad ()
Additional contact information
Hiam Chemaitelly: Qatar Foundation – Education City
Houssein H. Ayoub: Qatar University
Peter Coyle: Qatar University
Patrick Tang: Sidra Medicine
Mohammad R. Hasan: McMaster University
Hadi M. Yassine: Qatar University
Asmaa A. Al Thani: Qatar University
Zaina Al-Kanaani: Hamad Medical Corporation
Einas Al-Kuwari: Hamad Medical Corporation
Andrew Jeremijenko: Hamad Medical Corporation
Anvar Hassan Kaleeckal: Hamad Medical Corporation
Ali Nizar Latif: Hamad Medical Corporation
Riyazuddin Mohammad Shaik: Hamad Medical Corporation
Hanan F. Abdul-Rahim: Qatar University
Gheyath K. Nasrallah: Qatar University
Mohamed Ghaith Al-Kuwari: Primary Health Care Corporation
Adeel A. Butt: Cornell University
Hamad Eid Al-Romaihi: Ministry of Public Health
Mohamed H. Al-Thani: Ministry of Public Health
Abdullatif Al-Khal: Hamad Medical Corporation
Roberto Bertollini: Ministry of Public Health
Laith J. Abu-Raddad: Qatar Foundation – Education City

Nature, 2025, vol. 639, issue 8056, 1024-1031

Abstract: Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved over short timescales, leading to the emergence of more transmissible variants such as Alpha and Delta1–3. The arrival of the Omicron variant marked a major shift, introducing numerous extra mutations in the spike gene compared with earlier variants1,2. These evolutionary changes have raised concerns regarding their potential impact on immune evasion, disease severity and the effectiveness of vaccines and treatments1,3. In this epidemiological study, we identified two distinct patterns in the protective effect of natural infection against reinfection in the Omicron versus pre-Omicron eras. Before Omicron, natural infection provided strong and durable protection against reinfection, with minimal waning over time. However, during the Omicron era, protection was robust only for those recently infected, declining rapidly over time and diminishing within a year. These results demonstrate that SARS-CoV-2 immune protection is shaped by a dynamic interaction between host immunity and viral evolution, leading to contrasting reinfection patterns before and after Omicron’s first wave. This shift in patterns suggests a change in evolutionary pressures, with intrinsic transmissibility driving adaptation pre-Omicron and immune escape becoming dominant post-Omicron, underscoring the need for periodic vaccine updates to sustain immunity.

Date: 2025
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DOI: 10.1038/s41586-024-08511-9

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