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We estimated the South African SARS-CoV-2 disease burden and severity, describing changes in the shape of the disease burden pyramid with successive waves.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We estimated SARS-CoV-2 medically and non-medically attended illness stratified by severity (mild, severe non-fatal and fatal) during the initial five waves, spanning 1 March 2020 through 13 August 2022. We used individual-level national surveillance, healthcare utilisation and serosurvey data to estimate wave-specific hospitalisation-fatality (HFR) and infection-fatality ratios. We estimated wave-specific incidence rates per 100\u2009000 population with 95% CIs derived from bootstrapping the individual-level data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>On 13 August 2022, the estimated cumulative number of SARS-CoV-2 infections in South Africa was 104.6\u2009million, of which 399\u2009900 (0.38%) were severe non-fatal and 258\u2009800-289 000 (0.25 - 0.28%) fatal. 29% of severe non-fatal illness and 55 - 60% of deaths occurred outside the hospital. The highest burden of severe and fatal illness was during the Delta wave (wave 3), and the HFR across the initial three waves was similar (range 31\u201334%). Although there were more infections during the Omicron BA.1 wave (wave 4), there was a substantial reduction in HFR (14%). Successive waves saw a reduction in the rate of increase in mortality and hospitalisations with increasing age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The substantial South African national burden of SARS-CoV-2 for the initial five waves contradicts the belief of minimal impact in Africa. A high proportion of severe non-fatal and fatal illness occurred outside of the hospital, highlighting the importance of studies of health-seeking and vital registration systems to document the full burden of illness. The highest burden of severe illness and death was in the Delta wave. Following the Omicron emergence, severe illness reduced, and with successive waves, proportionately more children were infected and became ill, suggesting a transition to a more endemic pattern.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjph-2024-002174","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T06:35:25Z","timestamp":1763793325000},"page":"e002174","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Burden of SARS-CoV-2 infection and severe illness in South Africa (March 2020\u2013August 2022): a synthesis of epidemiological data"],"prefix":"10.1136","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7879-2173","authenticated-orcid":false,"given":"Larisse","family":"Bolton","sequence":"first","affiliation":[{"name":"South African Centre for Epidemiological Modelling and Analysis (SACEMA), School for Data Science and Computational Thinking, 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South African Medical Research Council, Cape Town, South Africa"},{"name":"Department of Family Medicine and Public Health, University of Cape Town, Rondebosch, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6865-9739","authenticated-orcid":false,"given":"Rob","family":"Dorrington","sequence":"additional","affiliation":[{"name":"Centre for Actuarial Research (CARe), University of Cape Town, Rondebosch, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7081-6273","authenticated-orcid":false,"given":"Jackie","family":"Kleynhans","sequence":"additional","affiliation":[{"name":"Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa"},{"name":"School of Public Health, University of the Witwatersrand, Johannesburg, South 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