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

Houriiyah Tegally; Monika Moir; Josie Everatt; Marta Giovanetti; Cathrine Scheepers; Eduan Wilkinson; Kathleen Subramoney; Zinhle Makatini; Sikhulile Moyo; Daniel G. Amoako; Cheryl Baxter; Christian L. Althaus; Ugochukwu J. Anyaneji; Dikeledi Kekana; Raquel Viana; Jennifer Giandhari; Richard J. Lessells; Tongai Maponga; Dorcas Maruapula; Wonderful Choga; Mogomotsi Matshaba; Mpaphi B. Mbulawa; Nokukhanya Msomi; Yeshnee Naidoo; Sureshnee Pillay; Tomasz Janusz Sanko; James E. San; Lesley Scott; Lavanya Singh; Nonkululeko A. Magini; Pamela Smith-Lawrence; Wendy Stevens; Graeme Dor; Derek Tshiabuila; Nicole Wolter; Wolfgang Preiser; Florette K. Treurnicht; Marietjie Venter; Georginah Chiloane; Caitlyn Mcintyre; Aine O’toole; Christopher Ruis; Thomas P. Peacock; Cornelius Roemer; Sergei L. Kosakovsky Pond; Carolyn Williamson; Oliver G. Pybus; Jinal N. Bhiman; Allison Glass; Darren P. Martin; Ben Jackson; Andrew Rambaut; Oluwakemi Laguda-Akingba; Simani Gaseitsiwe; Anne Von Gottberg; Tulio De Oliveira

doi:10.1038/s41591-022-01911-2

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

Houriiyah Tegally, Monika Moir, Josie Everatt, Marta Giovanetti, Cathrine Scheepers, Eduan Wilkinson, Kathleen Subramoney, Zinhle Makatini, Sikhulile Moyo, Daniel G. Amoako, Cheryl Baxter, Christian L. Althaus, Ugochukwu J. Anyaneji, Dikeledi Kekana, Raquel Viana, Jennifer Giandhari, Richard J. Lessells, Tongai Maponga, Dorcas Maruapula, Wonderful ChogaMogomotsi Matshaba, Mpaphi B. Mbulawa, Nokukhanya Msomi, Yeshnee Naidoo, Sureshnee Pillay, Tomasz Janusz Sanko, James E. San, Lesley Scott, Lavanya Singh, Nonkululeko A. Magini, Pamela Smith-Lawrence, Wendy Stevens, Graeme Dor, Derek Tshiabuila, Nicole Wolter, Wolfgang Preiser, Florette K. Treurnicht, Marietjie Venter, Georginah Chiloane, Caitlyn Mcintyre, Aine O’toole, Christopher Ruis, Thomas P. Peacock, Cornelius Roemer, Sergei L. Kosakovsky Pond, Carolyn Williamson, Oliver G. Pybus, Jinal N. Bhiman, Allison Glass, Darren P. Martin, Ben Jackson, Andrew Rambaut, Oluwakemi Laguda-Akingba, Simani Gaseitsiwe, Anne Von Gottberg, Tulio De Oliveira

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	1785-1790
Number of pages	18
Journal	Nature Medicine
Volume	28
Issue number	9
Early online date	27 Jun 2022
DOIs	https://doi.org/10.1038/s41591-022-01911-2
Publication status	Published - 1 Sept 2022

Keywords / Materials (for Non-textual outputs)

Amino Acids
Animals
COVID-19/epidemiology
Humans
SARS-CoV-2/genetics
South Africa/epidemiology
Spike Glycoprotein, Coronavirus/genetics

Access to Document

10.1038/s41591-022-01911-2Licence: Creative Commons: Attribution (CC-BY)

deOliveiraEtalNM2022EmergenceOfSARS-CoV-2Final published version, 6.23 MBLicence: Creative Commons: Attribution (CC-BY)

Cite this

Tegally, H., Moir, M., Everatt, J., Giovanetti, M., Scheepers, C., Wilkinson, E., Subramoney, K., Makatini, Z., Moyo, S., Amoako, D. G., Baxter, C., Althaus, C. L., Anyaneji, U. J., Kekana, D., Viana, R., Giandhari, J., Lessells, R. J., Maponga, T., Maruapula, D., ... De Oliveira, T. (2022). Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa. Nature Medicine, 28(9), 1785-1790. Advance online publication. https://doi.org/10.1038/s41591-022-01911-2

@article{e4469a25526c472c9954c9a596e94bea,

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

abstract = "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{\textquoteright}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.",

keywords = "Amino Acids, Animals, COVID-19/epidemiology, Humans, SARS-CoV-2/genetics, South Africa/epidemiology, Spike Glycoprotein, Coronavirus/genetics",

author = "Houriiyah Tegally and Monika Moir and Josie Everatt and Marta Giovanetti and Cathrine Scheepers and Eduan Wilkinson and Kathleen Subramoney and Zinhle Makatini and Sikhulile Moyo and Amoako, {Daniel G.} and Cheryl Baxter and Althaus, {Christian L.} and Anyaneji, {Ugochukwu J.} and Dikeledi Kekana and Raquel Viana and Jennifer Giandhari and Lessells, {Richard J.} and Tongai Maponga and Dorcas Maruapula and Wonderful Choga and Mogomotsi Matshaba and Mbulawa, {Mpaphi B.} and Nokukhanya Msomi and Yeshnee Naidoo and Sureshnee Pillay and Sanko, {Tomasz Janusz} and San, {James E.} and Lesley Scott and Lavanya Singh and Magini, {Nonkululeko A.} and Pamela Smith-Lawrence and Wendy Stevens and Graeme Dor and Derek Tshiabuila and Nicole Wolter and Wolfgang Preiser and Treurnicht, {Florette K.} and Marietjie Venter and Georginah Chiloane and Caitlyn Mcintyre and Aine O{\textquoteright}toole and Christopher Ruis and Peacock, {Thomas P.} and Cornelius Roemer and Pond, {Sergei L. Kosakovsky} and Carolyn Williamson and Pybus, {Oliver G.} and Bhiman, {Jinal N.} and Allison Glass and Martin, {Darren P.} and Ben Jackson and Andrew Rambaut and Oluwakemi Laguda-Akingba and Simani Gaseitsiwe and {Von Gottberg}, Anne and {De Oliveira}, Tulio",

note = "Funding Information: This research was supported by 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). The content and findings reported herein are the sole deduction, view and responsibility of the researchers and do not reflect the official position and sentiments of the funding agencies. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = sep,

day = "1",

doi = "10.1038/s41591-022-01911-2",

language = "English",

volume = "28",

pages = "1785--1790",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

number = "9",

}

Tegally, H, Moir, M, Everatt, J, Giovanetti, M, Scheepers, C, Wilkinson, E, Subramoney, K, Makatini, Z, Moyo, S, Amoako, DG, Baxter, C, Althaus, CL, Anyaneji, UJ, Kekana, D, Viana, R, Giandhari, J, Lessells, RJ, Maponga, T, Maruapula, D, Choga, W, Matshaba, M, Mbulawa, MB, Msomi, N, Naidoo, Y, Pillay, S, Sanko, TJ, San, JE, Scott, L, Singh, L, Magini, NA, Smith-Lawrence, P, Stevens, W, Dor, G, Tshiabuila, D, Wolter, N, Preiser, W, Treurnicht, FK, Venter, M, Chiloane, G, Mcintyre, C, O’toole, A, Ruis, C, Peacock, TP, Roemer, C, Pond, SLK, Williamson, C, Pybus, OG, Bhiman, JN, Glass, A, Martin, DP, Jackson, B, Rambaut, A, Laguda-Akingba, O, Gaseitsiwe, S, Von Gottberg, A & De Oliveira, T 2022, 'Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa', Nature Medicine, vol. 28, no. 9, pp. 1785-1790. https://doi.org/10.1038/s41591-022-01911-2

TY - JOUR

T1 - Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa

AU - Tegally, Houriiyah

AU - Moir, Monika

AU - Everatt, Josie

AU - Giovanetti, Marta

AU - Scheepers, Cathrine

AU - Wilkinson, Eduan

AU - Subramoney, Kathleen

AU - Makatini, Zinhle

AU - Moyo, Sikhulile

AU - Amoako, Daniel G.

AU - Baxter, Cheryl

AU - Althaus, Christian L.

AU - Anyaneji, Ugochukwu J.

AU - Kekana, Dikeledi

AU - Viana, Raquel

AU - Giandhari, Jennifer

AU - Lessells, Richard J.

AU - Maponga, Tongai

AU - Maruapula, Dorcas

AU - Choga, Wonderful

AU - Matshaba, Mogomotsi

AU - Mbulawa, Mpaphi B.

AU - Msomi, Nokukhanya

AU - Naidoo, Yeshnee

AU - Pillay, Sureshnee

AU - Sanko, Tomasz Janusz

AU - San, James E.

AU - Scott, Lesley

AU - Singh, Lavanya

AU - Magini, Nonkululeko A.

AU - Smith-Lawrence, Pamela

AU - Stevens, Wendy

AU - Dor, Graeme

AU - Tshiabuila, Derek

AU - Wolter, Nicole

AU - Preiser, Wolfgang

AU - Treurnicht, Florette K.

AU - Venter, Marietjie

AU - Chiloane, Georginah

AU - Mcintyre, Caitlyn

AU - O’toole, Aine

AU - Ruis, Christopher

AU - Peacock, Thomas P.

AU - Roemer, Cornelius

AU - Pond, Sergei L. Kosakovsky

AU - Williamson, Carolyn

AU - Pybus, Oliver G.

AU - Bhiman, Jinal N.

AU - Glass, Allison

AU - Martin, Darren P.

AU - Jackson, Ben

AU - Rambaut, Andrew

AU - Laguda-Akingba, Oluwakemi

AU - Gaseitsiwe, Simani

AU - Von Gottberg, Anne

AU - De Oliveira, Tulio

N1 - Funding Information: This research was supported by 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). The content and findings reported herein are the sole deduction, view and responsibility of the researchers and do not reflect the official position and sentiments of the funding agencies. Publisher Copyright: © 2022, The Author(s).

PY - 2022/9/1

Y1 - 2022/9/1

N2 - 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.

AB - 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.

KW - Amino Acids

KW - Animals

KW - COVID-19/epidemiology

KW - Humans

KW - SARS-CoV-2/genetics

KW - South Africa/epidemiology

KW - Spike Glycoprotein, Coronavirus/genetics

UR - https://github.com/krisp-kwazulu-natal/SARSCoV2_South_Africa_Omicron_BA4_BA5

U2 - 10.1038/s41591-022-01911-2

DO - 10.1038/s41591-022-01911-2

M3 - Article

C2 - 35760080

SN - 1078-8956

VL - 28

SP - 1785

EP - 1790

JO - Nature Medicine

JF - Nature Medicine

IS - 9

ER -

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

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

Other files and links

Fingerprint

Cite this