Continued Emergence and Evolution of Omicron in South Africa: New BA.4 and BA.5 lineages

South Africa’s fourth COVID-19 wave was driven predominantly by three lineages (BA.1, BA.2 and BA.3) of the SARS-CoV-2 Omicron variant of concern. We have now identified two new lineages, BA.4 and BA.5. The spike proteins of BA.4 and BA.5 are identical, and comparable to BA.2 except for the addition of 69-70del, L452R, F486V and the wild type amino acid at Q493. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure with the TaqPath™ COVID-19 qPCR assay. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa from the first week of April 2022 onwards. Using a multinomial logistic regression model, we estimate growth advantages for BA.4 and BA.5 of 0.08 (95% CI: 0.07 - 0.09) and 0.12 (95% CI: 0.09 - 0.15) per day respectively over BA.2 in South Africa. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by the South African Medical Research Council (SAMRC) with funds received from the National Department of Health. Sequencing activities for NICD are supported by a conditional grant from the South African National Department of Health as part of the emergency COVID-19 response; a cooperative agreement between the National Institute for Communicable Diseases of the National Health Laboratory Service and the United States Centers for Disease Control and Prevention (CDC)(grant number 5 U01IP001048-05-00; 1 NU51IP000930-01-00); the African Society of Laboratory Medicine (ASLM) and Africa Centers for Disease Control and Prevention through a sub-award from the Bill and Melinda Gates Foundation grant number INV-018978; the UK Foreign, Commonwealth and Development Office and Wellcome (Grant no 221003/Z/20/Z); and the UK Department of Health and Social Care and managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project. This research was also supported by The Coronavirus Aid, Relief, and Economic Security Act (CARES ACT) through the CDC and the COVID International Task Force (ITF) funds through the CDC under the terms of a subcontract with the African Field Epidemiology Network (AFENET) AF-NICD-001/2021. Sequencing activities at KRISP and CERI are supported in part by grants from the World Health Organization, the Abbott Pandemic Defense Coalition (APDC), the National Institute of Health USA (U01 AI151698) for the United World Antivirus Research Network (UWARN) and the INFORM Africa project through IHVN (U54 TW012041), and the South African Department of Science and Innovation (SA DSI) and the SAMRC under the BRICS JAF #2020/049 ### 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 project was approved by University of KwaZulu-Natal Biomedical Research Ethics Committee (ref. BREC/00001510/2020), the University of the Witwatersrand Human Research Ethics Committee (HREC) (ref. M180832), Stellenbosch University HREC (ref. N20/04/008 COVID-19) and the University of Cape Town HREC (ref. 383/2020). Individual participant consent was not required for the genomic surveillance. This requirement was waived by the Research Ethics Committees. 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 are available online at GISAID database.