Population Based SARS-CoV-2 Sero-Epidemiological Survey and Estimated Infection Incidence and Fatality Risk in Gauteng Province, South Africa

Background: Limitations in laboratory testing capacity undermine the ability to quantify the overall burden of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. We undertook a cross-sectional population based sero-survey for SARS-CoV-2 infection in 26 sub-districts, Gauteng Province (population 15·9 million), South Africa. Furthermore, we estimated SARS-CoV-2 mortality risk triangulating seroprevalence, recorded COVID-19 deaths and excess mortality data. Methods: We employed multi-stage random household sampling with selection probability proportional to sub-district size, stratifying sub-district census-sampling frame by housing type and selecting clusters within household type strata. Serum SARS-CoV-2 receptor binding domain (RBD) Immunoglobulin G (IgG) was measured using a quantitative assay on Luminex platform. Findings: Overall RBD IgG seroprevalence was 19·1% (95%Confidence interval [CI]: 18·1-20·1%), being similar in children and adults. Seroprevalence varied from 5·5% to 43·2% across sub-districts. Conservatively, there were 2 897 120 (95%CI: 2 743 907-3 056 866) SARS-CoV-2 infections, yielding an incidence of 19 090 per 100 000 until January 9, 2021, when 330 336 COVID-19 cases were recorded.  The estimated mortality risk using recorded COVID-19 deaths (n=8198) was 0·28% (95%CI: 0·27-0·30) and 0·67% (95%CI: 0·64-0·71) assuming 90% of modelled natural excess deaths were due to COVID-19 (n=21 582). Notably, 53·8% (65/122) of individuals with previous self-reported confirmed SARS-CoV-2 infection were RBD IgG sero-negative. Interpretation: The imputed number of SARS-CoV-2 infections was 8·8 fold greater than recorded number of COVID-19 cases. The imputed SARS-CoV-2 infection mortality risk varied 2·39 fold when calculated using reported COVID-19 deaths (0·28%) compared with excess mortality derived COVID-19 attributable deaths (0·67%). Waning of RBD IgG may have inadvertently under-estimated number of SARS-CoV-2 infections, and conversely over-estimated mortality risk, by a factor of two.  Funding Information: Bill and Melinda Gates Foundation. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The University of the Witwatersrand Human Research Ethics Committee granted a waiver for formal approval of the survey, which was deemed to be part of public-health good and surveillance to manage the COVID-19 pandemic. Electronic signed informed consent was administered to individuals older than 15 years age, parental consent obtained for children <12 years of age, and assent and parental consent for adolescents 12-15 years old.