Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in southern Africa has been characterised by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, whilst the second and third waves were driven by the Beta and Delta variants, respectively1-3. In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng Province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, predicted to influence antibody neutralization and spike function4. Here, we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity

Emergence and phenotypic characterization of the global SARS-CoV-2 C.1.2 lineage

CODE AVAILABILITY : The R and python scripts used to generate figures (excluding bar charts) in this paper are available at https://github.com/NICD-CRDM/C.1.2_scripts. The Nextstrain build profile, other scripts required to run the custom pipeline, and GISAID accession identifiers for all sequences in the final tree are available at https://github.com/NICD-CRDM/ C.1.2_scripts/tree/main/Nextstrain_files. The MATLAB scripts used for microscopy are available at https://github.com/NICD-CRDM/C.1.2_scripts/tree/main/microscopy. This code is also available in Supplementary Software 1.DATA AVAILABILITY : All of the global SARS-CoV-2 genomes generated and presented in this article are publicly accessible through the GISAID9 platform (https://www.gisaid.org/), along with all other SARS-CoV-2 genomes generated by the NGS-SA. The GISAID accession identifiers of the C.1.2 sequences analyzed in this study are provided as part of Supplementary Tables 1 and 2, which also contain the metadata for the sequences. The Nextstrain build of C.1.2 and global sequences is available at https://nextstrain.org/ groups/ngs-sa/COVID19-C.1.2-2022-01-05. The GISAID accession identifiers for the full set of sequences used in this build can be accessed at https://github.com/NICD-CRDM/ C.1.2_scripts/tree/main/Nextstrain_files. The GISAID accession identifiers for the sequences used in Supp. Fig. 2a and temporal analysis can be accessed at https:// github.com/NICD-CRDM/C.1.2_scripts in the files violin_plot_IDs.xlsx and C.1.2_global_tempest.xlsx respectively. The shapefile used for South African maps in Supplementary Fig. 1 was downloaded from https://gadm.org/ (licensed for use in academic publications, see https://gadm.org/license.html) and visualised in R with ggplot2. The global map in Supplementary Fig. 1 was obtained from the rnaturalearth package (public domain, see https://docs.ropensci.org/rnaturalearth/articles/ rnaturalearth.html) and visualised with ggplot2. The data was based on sequences available on GISAID at the time.Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The initial C.1.2 detection is associated with a high substitution rate, and includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 variants of concern or variants of interest. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta show high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2.The Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation. Sequencing activities for the different sequencing hubs were provided 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; 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; the UK Foreign, Commonwealth and Development Office and Wellcome; the South African Medical Research Council; the UK Department of Health and Social Care and managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project; German Federal Ministry of Education and Research for the African Network for Improved Diagnostics, Epidemiology and Management of common infectious Agents (ANDEMIA). This study was supported by the Bill and Melinda Gates award, National Institutes of Health, South African Medical Research Council and National Institutes of Health. Hyrax Biosciences’ Exatype platform was supported by the South African Medical Research Council with funds received from the Department of Science and Innovation.http://www.nature.com/naturecommunicationsam2023Medical VirologyVeterinary Tropical DiseasesSDG-03:Good heatlh and well-bein

Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa

DATA AVAILABILITY : All of the SARS-CoV-2 genomes generated and presented in this article are publicly accessible through the GISAID platform (https://www.gisaid.org/). The GISAID accession identifiers of the sequences analyzed in this study are provided as part of Supplementary Table 1. Other raw data for this study are provided as a supplementary dataset at https://github.com/krisp-kwazulu-natal/SARSCoV2_South_Africa_Omicron_BA4_BA5. The reference SARS-CoV-2 genome (MN908947.3) was downloaded from the National Center for Biotechnology Information database (https://www.ncbi.nlm.nih.gov/).CODE AVAILABILITY : All custom scripts to reproduce the analyses and figures presented in this article are available at https://github.com/krisp-kwazulu-natal/ SARSCoV2_South_Africa_Omicron_BA4_BA5.Three lineages (BA.1, BA.2 and BA.3) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern predominantly drove South Africa’s fourth Coronavirus Disease 2019 (COVID-19) wave. We have now identified two new lineages, BA.4 and BA.5, responsible for a fifth wave of infections. The spike proteins of BA.4 and BA.5 are identical, and similar to BA.2 except for the addition of 69–70 deletion (present in the Alpha variant and the BA.1 lineage), L452R (present in the Delta variant), F486V and the wild-type amino acid at Q493. The two lineages differ only outside of the spike region. The 69–70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure, on the background of variants not possessing this feature. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa by the first week of April 2022. Using a multinomial logistic regression model, we estimated growth advantages for BA.4 and BA.5 of 0.08 (95% confidence interval (CI): 0.08–0.09) and 0.10 (95% CI: 0.09–0.11) per day, respectively, over BA.2 in South Africa. The continued discovery of genetically diverse Omicron lineages points to the hypothesis that a discrete reservoir, such as human chronic infections and/or animal hosts, is potentially contributing to further evolution and dispersal of the virus.The South African Medical Research Council (SAMRC) with funds received from the National Department of Health. Sequencing activities for the National Institute for Communicable Diseases (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 NICD of the NHLS and the US Centers for Disease Control and Prevention (CDC) (U01IP001048 and 1 NU51IP000930); 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 (221003/Z/20/Z); and the UK Department of Health and Social Care, 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 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 the Centre for Epidemic Response and Innovation are supported, in part, by grants from the World Health Organization, the Rockefeller Foundation (HTH 017), the Abbott Pandemic Defense Coalition (APDC), the US National Institutes of Health (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). Sequencing at the Botswana Harvard AIDS Institute Partnership was supported by funding from the Bill and Melinda Gates Foundation, the Foundation for Innovation in Diagnostics, the National Institutes of Health Fogarty International Centre (3D43TW009610-09S1) and the HHS/NIH/ National Institute of Allergy and Infectious Diseases (NIAID) (5K24AI131928-04 and 5K24AI131924-04).http://www.nature.com/naturemedicineam2023Medical VirologySDG-03:Good heatlh and well-bein