Background: This study assessed the evolution of COVID-19 severity and fatality by utilizing rigorous and standardized criteria that were consistently applied throughout the pandemic in Qatar. Methods: A national cohort study was conducted on Qataris, using data on COVID-19 acute-care and ICU hospitalizations, as well as severe, critical, and fatal COVID-19 cases classified according to the World Health Organization criteria. Results: The cumulative incidence of severe, critical, or fatal COVID-19 after 3.14 years of follow-up was 0.45% (95% CI: 0.43-0.47%). The incidence rate for severe, critical, or fatal COVID-19 throughout the pandemic was 1.43 (95% CI: 1.35-1.50) per 1,000 person-years. In the pre-omicron phase, first omicron wave, and combined phases, it was 2.01 (95% CI: 1.90-2.13), 3.70 (95% CI: 3.25-4.22), and 2.18 (95% CI: 2.07-2.30) per 1,000 person-years, respectively. The post-first omicron phase saw a drastic drop to 0.10 (95% CI: 0.08-0.14) per 1,000 person-years, a 95.4% reduction. Among all severe, critical, and fatal cases, 99.5% occurred during the primary infection. The cumulative incidence of fatal COVID-19 was 0.042% (95% CI: 0.036-0.050%), with an incidence rate of 0.13 (95% CI: 0.11-0.16) per 1,000 person-years. In the post-first omicron phase, the incidence rate of fatal COVID-19 decreased by 90.0% compared to earlier stages. Both severity and fatality exhibited an exponential increase with age and a linear increase with the number of coexisting conditions. Conclusions: The conclusion of the first omicron wave was a turning point in the severity of the pandemic. While vaccination and enhanced case management reduced severity gradually, the rapid accumulation of natural immunity during the initial omicron wave appears to have played the crucial role in driving this shift in severity.

The authors have declared no competing interest.

The authors are grateful for institutional salary support from the Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, as well as for institutional salary support provided by the Ministry of Public Health, Hamad Medical Corporation, and Sidra Medicine. The authors are also grateful for the Qatar Genome Programme and Qatar University Biomedical Research Center for institutional support for the reagents needed for the viral genome sequencing. HHA acknowledges the support of Qatar University Internal Grant ID QUCG-CAS-23/24-114. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the article. Statements made herein are solely the responsibility of the authors.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Hamad Medical Corporation and Weill Cornell Medicine in Qatar Institutional Review Boards approved this retrospective study with a waiver of informed consent.

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The dataset of this study is a property of the Qatar Ministry of Public Health that was provided to the researchers through a restricted-access agreement that prevents sharing the dataset with a third party or publicly. The data are available under restricted access for preservation of confidentiality of patient data. Access can be obtained through a direct application for data access to Her Excellency the Minister of Public Health (https:// www.moph.gov.qa/english/OurServices/eservices/Pages/Governmental-HealthCommunication-Center.aspx). The raw data are protected and are not available due to data privacy laws. Aggregate data are available within the paper and its supplementary information.