South African study shows COVID severity of Omicron BA.1, BA.4, BA.5 all similar

A recent article posted to the medRxiv* preprint server analyzed the illness severity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.4/BA.5 and prior viral waves in the Western Cape, South Africa.

Study: Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa. Image Credit: Cryptographer / Shutterstock


Since November 2021, the SARS-CoV-2 Omicron variant of concern (VOC) has dominated the world, with numerous lineages producing spikes in infection rates.

Between November 2021 and January 2022, there was an initial, significant Omicron BA.1 infection increase in South Africa. Shortly, the Omicron BA.2 variant superseded BA.1, which did not increase the number of cases. Subsequently, the Omicron BA.4/BA.5 variant caused an upsurge of SARS-CoV-2 cases from April to June 2022.

Omicron BA.4/BA.5 VOC mutations appear to give an advantage in growth over the BA.2 variant and immune evasion from BA.1-elicited and vaccine-derived antibodies. Importantly, the global reports of BA.5 and BA.4 infections are increasing currently.

About the study

In the present research, the scientists compared the clinical severity of SARS-CoV-2 Omicron BA.5/BA.4 infection with Omicron BA.1 and earlier SARS-CoV-2 variant infections across laboratory-validated CoV disease 2019 (COVID-19) cases in the Western Cape, South Africa, using the timeframe of infection to deduce the variant/lineage causing infection.

The team recruited public sector patients aged 20 years or older with laboratory-validated SARS-CoV-2 infection between May 1 and 21, 2022 (BA.4/BA.5 wave timeframe) and similar earlier wave periods for the study. The laboratory-validated COVID-19 comprised either a positive SARS-CoV-2 antigen or polymerase chain reaction (PCR) test. 

During the present assessment, the SARS-CoV-2 waves were characterized as beginning and terminating when the public sector COVID-19-linked hospitalizations' seven-day moving average rose above and fell below five and 12 per million people, respectively. The authors considered cases identified one week before the wave initiation and a week before the wave end date to address the delay between infection, initial symptoms, and hospitalization.

The investigators used Cox regression controlled for comorbidities, demographics, COVID-19 vaccination, admission pressure, and previous SARS-CoV-2 infection to compare the risk of 1) mortality and 2) severe hospitalization/mortality within three weeks of diagnosis between the BA.4/BA.5 wave and the four previous waves.


The study results indicated that the analysis encompassed 190,836 patients from earlier four COVID-19 waves and 3,793 patients from the SARS-CoV-2 Omicron BA.4/BA.5 wave. The authors discovered no variance in the risk of severe COVID-19 hospitalization or fatality between the SARS-CoV-2 BA.4/BA.5 timespan and the BA.1 timespan, both of which had improved outcomes than earlier COVID-19 waves, using the diagnosis timing as a proxy for being infected with various Omicron lineages in the Western Cape.

The team did not directly compare BA.4/BA.5 with BA.2, as BA.2 outbreak in the Western Cape did not result in a discernible increase in infections. Furthermore, earlier reports demonstrated a similar illness severity between BA.2 and BA.1.

Prior SARS-CoV-2 infection or three homologous doses of COVID-19 BNT162b2 or Ad26.COV2.S vaccines or a heterologous combination of these provided robust immunity against severe SARS-CoV-2, with the latter providing 73% protection against severe SARS-CoV-2 hospitalization or mortality among laboratory-validated cases in the BA.4/5 wave.

Indeed, the discovery of less severe COVID-19 outcomes during BA.4/BA.5 compared to BA.1 in models without accounting for prior diagnosed infection and vaccination implies that the identified continued ecologic divergence of SARS-CoV-2 cases and severe outcomes were at least partially due to burgeoning protection against severe illness from both vaccination and prior infection.

Besides, the scientists noted that the exact burden of hospitalizations and deaths was substantially lower in the BA.5/BA.4 waves than depicted by them, with the peak seven-day moving average of hospitalizations and deaths was 222 and 36 in the BA.1 wave relative to 66 and nine in the BA.4/BA.5 wave.


The authors claimed that the current investigation was one among the initial to compare the clinical severity of SARS-CoV-2 Omicron BA.4/BA.5 infections with the earlier virus variants with a comparatively extensive adjustment for vaccination and comorbidities across all confirmed cases.

The study findings depicted that in the context of heightening COVID-19 immunity due to vaccination and past infection, both of which were significantly protective, especially with booster vaccinations, COVID-19 severity among diagnosed cases in the SARS-CoV-2 Omicron BA.4/BA.5 and BA.1 eras was comparable. The team stated that ensuring that those at a high risk of developing severe SARS-CoV-2 outcomes receive at least three doses of the COVID-19 vaccine was still a relevant tactic for reducing the impact of future SARS-CoV-2 waves on the public health system.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa; Mary-Ann Davies, Erna Morden, Petro Rosseau, Juanita Arendse, Jamy-Lee Bam, Linda Boloko, Keith Cloete, Cheryl Cohen, Nicole Chetty, Pierre Dane, Alexa Heekes, Nei-Yuan Hsiao, Mehreen Hunter, Hannah Hussey, Theuns Jacobs, Waasila Jassat, Saadiq Kariem, Reshma Kassanjee, Inneke Laenen, Sue Le Roux, Richard Lessells, Hassan Mahomed, Deborah Maughan, Graeme Meintjes, Marc Mendelson, Ayanda Mnguni, Melvin Moodley, Katy Murie, Jonathan Naude, Ntobeko A.B. Ntusi, Masudah Paleker, Arifa Parker, David Pienaar, Wolfgang Preiser, Hans Prozesky, Peter Raubenheimer, Liezel Rossouw, Neshaad Schreuder, Barry Smith, Mariette Smith, Wesley Solomon, Greg Symons, Jantjie Taljaard, Sean Wasserman, Robert Wilkinson, Milani Wolmarans, Nicole Wolter, Andrew Boulle, Western Cape Department of Health and Wellness, National Departments of Health, National Institute for Communicable Diseases in South Africa. medRxiv preprint 2022. DOI:,

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Antibodies, Antigen, Coronavirus, Coronavirus Disease COVID-19, covid-19, Homologous, immunity, Laboratory, Mortality, Omicron, Polymerase, Polymerase Chain Reaction, Public Health, Research, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Vaccine, Virus

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Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.

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