Changing Epidemiology of COVID-19 in Children and Adolescents Over Four Successive Epidemic Waves in South Africa, 2020-2022

Background: South Africa experienced four initial waves of SARS-CoV-2 infection, dominated by Wuhan-Hu, Beta, Delta and Omicron (BA.1/BA.2) respectively. We describe the trends in SARS-CoV-2 testing, cases, admissions and deaths among children and adolescents in South Africa over successive waves. Methods: We analysed national COVID-19 testing, laboratory-confirmed case, and admissions data from 1 March 2020 to 5 February 2022 and estimated cumulative rates by age group for each endpoint. Severity in the third vs the fourth wave was assessed using multivariable logistic regression. Results: Individuals aged ≤18 years comprised 35% (21,008,060/60,142,978) of the population and 14% (3,006,244/22,105,970) of tests, 12% (424,394/3,593,644) of cases, 6% (26,176/451,753) of admissions and 0.7% (736/100,493) of deaths. Among individuals aged ≤18 years, infants had the highest cumulative testing (40,633/100,000 population) and admission (505/100,000) rates and 13-18-year olds had the highest case rate (3,609/100,000). In the first three waves, weekly testing, case and admission rates were consistently higher in adults aged >18 years, but in the fourth wave, weekly admissions in children aged <1 year (169/100,000) exceeded rates in adults (124/100,000). Of those admitted, children 1-4 years compared to adults were proportionately higher in the fourth wave than in the first wave (aOR 6.9, 95%CI 6.1-7.7) or the third wave (aOR 3.5, 95% CI 3.2-3.7). However, the proportion of admitted cases with severe COVID-19 in the fourth compared to the third wave was lower overall (aOR 0.3, 95%CI 0.3-0.3, P<0.001), and in each age group stratum. Discussion: During the fourth wave, rates of admission with positive COVID-19 tests were higher in children <5 years compared to previous waves with less severe outcomes, although data on whether admissions and deaths were COVID-19-attributable we not available. This increase in admissions may reflect the relative vulnerability of children who were not vaccinated, increased testing or increased exposure. Funding Information: This study was supported by the National Institute for Communicable Diseases and National Department of Health, Republic of South Africa. Declaration of Interests: CC has received grant support from Sanofi Pasteur, US CDC, Welcome Trust, Programme for Applied Technologies in Health (PATH), Bill & Melinda Gates Foundation and South African Medical Research Council (SA-MRC). AvG and NW have received grant support from Sanofi Pasteur and the Gates Foundation. MG has received grants from Bill & Melinda Gates Foundation and South African Medical Research Council. The remaining authors declare no conflict of interest. Ethics Approval Statement: The Human Research Ethics Committee of the University of the Witwatersrand granted ethical approval for the collection of COVID-19 case and test data as part of communicable disease surveillance (M210752), and the DATCOV surveillance program (M2010108).