SARS-CoV-2 infections during Omicron (BA.1) dominant wave and subsequent population immunity in Gauteng, South Africa

Background The B.1.1.529 (Omicron BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global resurgence of coronavirus disease 2019 (Covid-19). The contribution of BA.1 infection to population immunity and its effect on subsequent resurgence of B.1.1.529 sub-lineages warrant investigation. Methods We conducted an epidemiologic survey to determine the sero-prevalence of SARS-CoV-2 IgG from March 1 to April 11, 2022, after the BA.1-dominant wave had subsided in Gauteng (South Africa), and prior to a resurgence of Covid-19 dominated by the BA.4 and BA.5 (BA.4/BA.5) sub-lineages. Population-based sampling included households in an earlier survey from October 22 to December 9, 2021 preceding the BA.1 dominant wave. Dried-blood-spot samples were quantitatively tested for IgG against SARS-CoV-2 spike protein and nucleocapsid protein. Epidemiologic trends in Gauteng for cases, hospitalizations, recorded deaths, and excess deaths were evaluated from the inception of the pandemic to the onset of the BA.1 dominant wave (pre-BA.1), during the BA.1 dominant wave, and for the BA.4/BA.5 dominant wave through June 6, 2022. Results The 7510 participants included 2420 with paired samples from the earlier survey. Despite only 26.7% (1995/7470) of individuals having received a Covid-19 vaccine, the overall sero-prevalence was 90.9% (95% confidence interval [CI], 90.2 to 91.5), including 89.5% in Covid-19 unvaccinated individuals. Sixty-four percent (95%CI, 61.8-65.9) of individuals with paired samples had serological evidence of SARS-CoV-2 infection during the BA.1 dominant wave. Of all cumulative recorded hospitalisations and deaths, 14.1% and 5.9% were contributed by the BA.1 dominant wave, and 5.1% and 1.6% by the BA.4/BA.5 dominant wave. The SARS-CoV-2 infection fatality risk was lower in the BA.1 compared with pre-BA.1 waves for recorded deaths (0.02% vs. 0.33%) and Covid-19 attributable deaths based on excess mortality estimates (0.03% vs. 0.67%). Conclusions Gauteng province experienced high levels of infections in the BA.1 -dominant wave against a backdrop of high (73%) sero-prevalence. Covid-19 hospitalizations and deaths were further decoupled from infections during BA.4/BA.5 dominant wave than that observed during the BA.1 dominant wave. (Funded by the Bill and Melinda Gates Foundation.) ### Competing Interest Statement Dr. Mutevedzi, Dr Izu, Mr Mukendi, Dr Kwatra, Dr Blumberg, reports research grants from BMGF, during the conduct of the study. Dr. Madhi reports grants from BMGF, during the conduct of the study; grants and personal fees from BMGF, grants from NOVAVAX, grants from South African Medical Research Council, grants from GLAXO SMITH KLINE, grants from EDCTP, grants from MINERVAX, grants from AstraZeneca, grants from Pfizer, grants from Gritstone, grants from ImmunityBio, outside the submitted work. Dr. Jassat reports grants from Right to Care/PEPFAR, during the conduct of the study. Mr. Welch reports grants from BMGF, during the conduct of the study; other from Adcock Ingram Holdings Ltd, other from Aspen Pharmacare Holdings Ltd, other from Dischem Pharmacies Ltd, other from Discovery Ltd, other from Netcare Ltd, outside the submitted work. ### Funding Statement This study was funded by Bill and Melinda Gates Foundation ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The survey was done in partnership with Gauteng Department of Health as part of public health surveillance. The Human Research Ethics Committee at the University of the Witwatersrand granted a waiver for ethics approval of the survey. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript