Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages compared to BA.1 and Delta in South Africa

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Abstract

Omicron lineages BA.4 and BA.5 drove a fifth wave of COVID-19 cases in South Africa. Here, we use the presence/absence of the S-gene target as a proxy for SARS-CoV-2 variant/lineage for infections diagnosed using the TaqPath PCR assay between 1 October 2021 and 26 April 2022. We link national COVID-19 individual-level data including case, laboratory test and hospitalisation data. We assess severity using multivariable logistic regression comparing the risk of hospitalisation and risk of severe disease, once hospitalised, for Delta, BA.1, BA.2 and BA.4/BA.5 infections. After controlling for factors associated with hospitalisation and severe outcome respectively, BA.4/BA.5-infected individuals had a similar odds of hospitalisation (aOR 1.24, 95% CI 0.98–1.55) and severe outcome (aOR 0.72, 95% CI 0.41–1.26) compared to BA.1-infected individuals. Newly emerged Omicron lineages BA.4/BA.5 showed similar severity to the BA.1 lineage and continued to show reduced clinical severity compared to the Delta variant.

Abstract

South Africa experienced a resurgence in COVID-19 in 2022 driven by Omicron subvariants BA.4 and BA.5. Here, the authors investigate the severity of infections caused by these subvariants, and find no difference in the risk of severe outcomes when compared to Omicron BA.1, whilst all Omicron subvariants were less severe than Delta.

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Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study

Nicole Wolter, Waasila Jassat, Sibongile Walaza … (2022)

Background The SARS-CoV-2 omicron variant of concern was identified in South Africa in November, 2021, and was associated with an increase in COVID-19 cases. We aimed to assess the clinical severity of infections with the omicron variant using S gene target failure (SGTF) on the Thermo Fisher Scientific TaqPath COVID-19 PCR test as a proxy. Methods We did data linkages for national, South African COVID-19 case data, SARS-CoV-2 laboratory test data, SARS-CoV-2 genome data, and COVID-19 hospital admissions data. For individuals diagnosed with COVID-19 via TaqPath PCR tests, infections were designated as either SGTF or non-SGTF. The delta variant was identified by genome sequencing. Using multivariable logistic regression models, we assessed disease severity and hospitalisations by comparing individuals with SGTF versus non-SGTF infections diagnosed between Oct 1 and Nov 30, 2021, and we further assessed disease severity by comparing SGTF-infected individuals diagnosed between Oct 1 and Nov 30, 2021, with delta variant-infected individuals diagnosed between April 1 and Nov 9, 2021. Findings From Oct 1 (week 39), 2021, to Dec 6 (week 49), 2021, 161 328 cases of COVID-19 were reported in South Africa. 38 282 people were diagnosed via TaqPath PCR tests and 29 721 SGTF infections and 1412 non-SGTF infections were identified. The proportion of SGTF infections increased from two (3·2%) of 63 in week 39 to 21 978 (97·9%) of 22 455 in week 48. After controlling for factors associated with hospitalisation, individuals with SGTF infections had significantly lower odds of admission than did those with non-SGTF infections (256 [2·4%] of 10 547 vs 121 [12·8%] of 948; adjusted odds ratio [aOR] 0·2, 95% CI 0·1–0·3). After controlling for factors associated with disease severity, the odds of severe disease were similar between hospitalised individuals with SGTF versus non-SGTF infections (42 [21%] of 204 vs 45 [40%] of 113; aOR 0·7, 95% CI 0·3–1·4). Compared with individuals with earlier delta variant infections, SGTF-infected individuals had a significantly lower odds of severe disease (496 [62·5%] of 793 vs 57 [23·4%] of 244; aOR 0·3, 95% CI 0·2–0·5), after controlling for factors associated with disease severity. Interpretation Our early analyses suggest a significantly reduced odds of hospitalisation among individuals with SGTF versus non-SGTF infections diagnosed during the same time period. SGTF-infected individuals had a significantly reduced odds of severe disease compared with individuals infected earlier with the delta variant. Some of this reduced severity is probably a result of previous immunity. Funding The South African Medical Research Council, the South African National Department of Health, US Centers for Disease Control and Prevention, the African Society of Laboratory Medicine, Africa Centers for Disease Control and Prevention, the Bill & Melinda Gates Foundation, the Wellcome Trust, and the Fleming Fund.

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Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa

Juliet Pulliam, Cari van Schalkwyk, Nevashan Govender … (2022)

Here, we provide two methods for monitoring reinfection trends in routine surveillance data to identify signatures of changes in reinfection risk and apply these approaches to data from South Africa’s SARS-CoV-2 epidemic to date. While we found no evidence of increased reinfection risk associated with circulation of Beta (B.1.351) or Delta (B.1.617.2) variants, we find clear, population-level evidence to suggest immune evasion by the Omicron (B.1.1.529) variant in previously infected individuals in South Africa. Reinfections occurring between 01 November 2021 and 31 January 2022 were detected in individuals infected in all three previous waves, and there has been an increase in the risk of having a third infection since mid-November 2021.

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Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

Aekkachai Tuekprakhon, Jiandong Huo, Rungtiwa Nutalai … (2022)

The Omicron lineage of SARS-CoV-2, first described in November 2021, spread rapidly to become globally dominant and has split into a number of sub-lineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa’s Gauteng region uncovered two new sub-lineages, BA.4 and BA.5 which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences and, although closely related to BA.2, contain further mutations in the receptor binding domain of spike. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by serum from triple AstraZeneca or Pfizer vaccinated individuals compared to BA.1 and BA.2. Furthermore, using serum from BA.1 vaccine breakthrough infections there are likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections. SARS-CoV-2 Omicron BA.4 and BA.5 sublineages bear mutations that lead to their reduced neutralization by sera from triple vaccinated individuals when compared to the more recent BA.1 and BA.2. Importantly, sera from individuals with breakthrough BA.1 infections also show reduced neutralization, suggesting that repeat Omicron infections are likely in the population.

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Author and article information

Contributors

Nicole Wolter:

ORCID: http://orcid.org/0000-0002-9526-0133

nicolew@nicd.ac.za

Journal

Journal ID (nlm-ta): Nat Commun

Journal ID (iso-abbrev): Nat Commun

Title: Nature Communications

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2041-1723

Publication date (Electronic): 4 October 2022

Publication date PMC-release: 4 October 2022

Publication date Collection: 2022

Volume: 13

Electronic Location Identifier: 5860

Affiliations

[1 ]GRID grid.416657.7, ISNI 0000 0004 0630 4574, Centre for Respiratory Diseases and Meningitis, , National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service, ; Johannesburg, South Africa

[2 ]GRID grid.11951.3d, ISNI 0000 0004 1937 1135, School of Pathology, Faculty of Health Sciences, , University of the Witwatersrand, ; Johannesburg, South Africa

[3 ]GRID grid.416657.7, ISNI 0000 0004 0630 4574, Division of Public Health Surveillance and Response, , National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service, ; Johannesburg, South Africa

[4 ]GRID grid.481194.1, ISNI 0000 0004 0521 9642, Right to Care, ; Pretoria, South Africa

[5 ]GRID grid.11951.3d, ISNI 0000 0004 1937 1135, School of Public Health, Faculty of Health Sciences, , University of the Witwatersrand, ; Johannesburg, South Africa

[6 ]GRID grid.416657.7, ISNI 0000 0004 0630 4574, Centre for Tuberculosis, , National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service, ; Johannesburg, South Africa

[7 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, School of Health Sciences, College of Health Sciences, , University of KwaZulu-Natal, ; KwaZulu-Natal, South Africa

[8 ]GRID grid.416657.7, ISNI 0000 0004 0630 4574, Centre for HIV and STIs, , National Institute for Communicable Diseases of the National Health Laboratory Service, ; Johannesburg, South Africa

[9 ]GRID grid.11951.3d, ISNI 0000 0004 1937 1135, SA MRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, , University of the Witwatersrand, ; Johannesburg, South Africa

[10 ]GRID grid.412964.c, ISNI 0000 0004 0610 3705, Department of Biochemistry and Microbiology, Faculty of Science, Engineering and Agriculture, , University of Venda, ; Thohoyandou, South Africa

[11 ]GRID grid.416657.7, ISNI 0000 0004 0630 4574, Sequencing Core Facility, , National Institute for Communicable Diseases of the National Health Laboratory Service, ; Johannesburg, South Africa

[12 ]GRID grid.511132.5, ISNI 0000 0004 0500 3622, Lancet Laboratories, ; Johannesburg, South Africa

[13 ]GRID grid.416657.7, ISNI 0000 0004 0630 4574, National Health Laboratory Service (NHLS), ; Johannesburg, South Africa

[14 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, School of Laboratory Medicine and Medical Sciences, , University of KwaZulu Natal, ; Durban, South Africa

[15 ]GRID grid.7836.a, ISNI 0000 0004 1937 1151, Division of Medical Virology, , University of Cape Town, ; Cape Town, South Africa

[16 ]GRID grid.16463.36, ISNI 0000 0001 0723 4123, Department of Virology, , University of KwaZulu-Natal, ; Durban, South Africa

[17 ]Department of Clinical Microbiology & Infectious Diseases, CH Baragwanath Academic Hospital, Johannesburg, South Africa

[18 ]GRID grid.7836.a, ISNI 0000 0004 1937 1151, Western Cape Government: Health and Wellness, and School of Public Health and Family Medicine, , University of Cape Town, ; Cape Town, South Africa

Author information

Nicole Wolter http://orcid.org/0000-0002-9526-0133

Waasila Jassat http://orcid.org/0000-0003-4279-3056

Richard Welch http://orcid.org/0000-0001-8298-8697

Harry Moultrie http://orcid.org/0000-0001-9722-0699

Michelle J. Groome http://orcid.org/0000-0001-5893-3725

Daniel Gyamfi Amoako http://orcid.org/0000-0003-3551-3458

Josie Everatt http://orcid.org/0000-0002-0373-2093

Jinal N. Bhiman http://orcid.org/0000-0001-6354-4003

Cathrine Scheepers http://orcid.org/0000-0002-1683-0282

Mignon du Plessis http://orcid.org/0000-0001-9186-0679

Arshad Ismail http://orcid.org/0000-0003-4672-5915

Nei-yuan Hsiao http://orcid.org/0000-0003-4926-6216

Anne von Gottberg http://orcid.org/0000-0002-0243-7455

Cheryl Cohen http://orcid.org/0000-0003-0376-2302

Article

Publisher ID: 33614

DOI: 10.1038/s41467-022-33614-0

PMC ID: 9531215

PubMed ID: 36195617

SO-VID: cbf9cc32-f6a8-4ba8-9831-a29c4d181b67

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 24 June 2022

Date accepted : 23 September 2022

Funding

Funded by: FundRef https://doi.org/10.13039/501100001322, South African Medical Research Council (SAMRC);

Funded by: FundRef https://doi.org/10.13039/100000030, U.S. Department of Health & Human Services | Centers for Disease Control and Prevention (CDC);

Award ID: 5U01IP001048-05-00

Award Recipient : Nicole Wolter

Funded by: FundRef https://doi.org/10.13039/100004440, Wellcome Trust (Wellcome);

Award ID: 221003/Z/20/Z

Award Recipient : Nicole Wolter

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ScienceOpen disciplines: Uncategorized

Keywords: viral infection,risk factors,epidemiology,sars-cov-2

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ScienceOpen disciplines: Uncategorized

Keywords: viral infection, risk factors, epidemiology, sars-cov-2

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Clinical severity of SARS-CoV-2 Omicron BA.4 and BA.5 lineages compared to BA.1 and Delta in South Africa

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COVID-19 Research in and about Africa

Most cited references 15

Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study

Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa

Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

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