We conducted an epidemiologic survey to determine the seroprevalence of SARS-CoV-2 anti-nucleocapsid (anti-N) and anti-spike (anti-S) protein IgG from 1 March to 11 April 2022 after the BA.1-dominant wave had subsided in South Africa and prior to another wave dominated by the BA.4 and BA.5 (BA.4/BA.5) sub-lineages. We also analysed epidemiologic trends in Gauteng Province for cases, hospitalizations, recorded deaths, and excess deaths were evaluated from the inception of the pandemic through 17 November 2022. Despite only 26.7% (1995/7470) of individuals having received a COVID-19 vaccine, the overall seropositivity for SARS-CoV-2 was 90.9% (95% confidence interval (CI), 90.2 to 91.5) at the end of the BA.1 wave, and 64% (95% CI, 61.8 to 65.9) of individuals were infected during the BA.1-dominant wave. The SARS-CoV-2 infection fatality risk was 16.5–22.3 times lower in the BA.1-dominant wave compared with the pre-BA.1 waves for recorded deaths (0.02% vs. 0.33%) and estimated excess mortality (0.03% vs. 0.67%). Although there are ongoing cases of COVID-19 infections, hospitalization and death, there has not been any meaningful resurgence of COVID-19 since the BA.1-dominant wave despite only 37.8% coverage by at least a single dose of COVID-19 vaccine in Gauteng, South Africa.