Hiam Chemaitelly1,2,3, Nico Nagelkerke1, Houssein H Ayoub4, Peter Coyle5,6,7, Patrick Tang8, Hadi M Yassine6,9, Hebah A Al-Khatib6,9, Maria K Smatti6,9, Mohammad R Hasan8, Zaina Al-Kanaani5, Einas Al-Kuwari5, Andrew Jeremijenko5, Anvar Hassan Kaleeckal5, Ali Nizar Latif5, Riyazuddin Mohammad Shaik5, Hanan F Abdul-Rahim10, Gheyath K Nasrallah6,9, Mohamed Ghaith Al-Kuwari11, Adeel A Butt3,5,12, Hamad Eid Al-Romaihi13, Mohamed H Al-Thani13, Abdullatif Al-Khal5, Roberto Bertollini13, Laith J Abu-Raddad1,2,3,10. 1. Infectious Disease Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Doha, Qatar. 2. World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation - Education City, Doha, Qatar. 3. Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York, New York, USA. 4. Mathematics Program, Department of Mathematics, Statistics, and Physics, College of Arts and Sciences, Qatar University, Doha, Qatar. 5. Hamad Medical Corporation, Doha, Qatar. 6. Biomedical Research Center, QU Health, Qatar University, Doha, Qatar. 7. Wellcome-Wolfson Institute for Experimental Medicine, Queens University, Belfast, United Kingdom. 8. Department of Pathology, Sidra Medicine, Doha, Qatar. 9. Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha, Qatar. 10. Department of Public Health, College of Health Sciences, QU Health, Qatar University, Doha, Qatar. 11. Primary Health Care Corporation, Doha, Qatar. 12. Department of Medicine, Weill Cornell Medicine, Cornell University, New York, New York, USA. 13. Ministry of Public Health, Doha, Qatar.
Abstract
BACKGROUND: The future of the SARS-CoV-2 pandemic hinges on virus evolution and duration of immune protection of natural infection against reinfection. We investigated duration of protection afforded by natural infection, the effect of viral immune evasion on duration of protection, and protection against severe reinfection, in Qatar, between February 28, 2020 and June 5, 2022. METHODS: Three national, matched, retrospective cohort studies were conducted to compare incidence of SARS-CoV-2 infection and COVID-19 severity among unvaccinated persons with a documented SARS-CoV-2 primary infection, to incidence among those infection-naïve and unvaccinated. Associations were estimated using Cox proportional-hazard regression models. RESULTS: Effectiveness of pre-Omicron primary infection against pre-Omicron reinfection was 85.5% (95% CI: 84.8-86.2%). Effectiveness peaked at 90.5% (95% CI: 88.4-92.3%) in the 7th month after the primary infection, but waned to ~ 70% by the 16th month. Extrapolating this waning trend using a Gompertz curve suggested an effectiveness of 50% in the 22nd month and < 10% by the 32nd month. Effectiveness of pre-Omicron primary infection against Omicron reinfection was 38.1% (95% CI: 36.3-39.8%) and declined with time since primary infection. A Gompertz curve suggested an effectiveness of < 10% by the 15th month. Effectiveness of primary infection against severe, critical, or fatal COVID-19 reinfection was 97.3% (95% CI: 94.9-98.6%), irrespective of the variant of primary infection or reinfection, and with no evidence for waning. Similar results were found in sub-group analyses for those ≥50 years of age. CONCLUSIONS: Protection of natural infection against reinfection wanes and may diminish within a few years. Viral immune evasion accelerates this waning. Protection against severe reinfection remains very strong, with no evidence for waning, irrespective of variant, for over 14 months after primary infection.
BACKGROUND: The future of the SARS-CoV-2 pandemic hinges on virus evolution and duration of immune protection of natural infection against reinfection. We investigated duration of protection afforded by natural infection, the effect of viral immune evasion on duration of protection, and protection against severe reinfection, in Qatar, between February 28, 2020 and June 5, 2022. METHODS: Three national, matched, retrospective cohort studies were conducted to compare incidence of SARS-CoV-2 infection and COVID-19 severity among unvaccinated persons with a documented SARS-CoV-2 primary infection, to incidence among those infection-naïve and unvaccinated. Associations were estimated using Cox proportional-hazard regression models. RESULTS: Effectiveness of pre-Omicron primary infection against pre-Omicron reinfection was 85.5% (95% CI: 84.8-86.2%). Effectiveness peaked at 90.5% (95% CI: 88.4-92.3%) in the 7th month after the primary infection, but waned to ~ 70% by the 16th month. Extrapolating this waning trend using a Gompertz curve suggested an effectiveness of 50% in the 22nd month and < 10% by the 32nd month. Effectiveness of pre-Omicron primary infection against Omicron reinfection was 38.1% (95% CI: 36.3-39.8%) and declined with time since primary infection. A Gompertz curve suggested an effectiveness of < 10% by the 15th month. Effectiveness of primary infection against severe, critical, or fatal COVID-19 reinfection was 97.3% (95% CI: 94.9-98.6%), irrespective of the variant of primary infection or reinfection, and with no evidence for waning. Similar results were found in sub-group analyses for those ≥50 years of age. CONCLUSIONS: Protection of natural infection against reinfection wanes and may diminish within a few years. Viral immune evasion accelerates this waning. Protection against severe reinfection remains very strong, with no evidence for waning, irrespective of variant, for over 14 months after primary infection.