A complex immunological landscape emerges in South Africa after Omicron BA.1/BA.2

In a recent study published on the medRxiv* preprint server, researchers analyze sera obtained prior to, during, and following the period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.1 and BA.2 (BA.1/2) dominance to evaluate infection rates and changes in the immunological history of coronavirus disease 2019 (COVID-19) patients over time.

Previous studies have reported that Omicron is more transmissible and immune-evasive than previously circulating SARS-CoV-2 variants, which has led to the vast and rapid geographic spread of Omicron across the globe. Due to the lower severity of Omicron infections, limited diagnostic resources and testing, and high reinfection rates, the expansion of Omicron BA.1/2 subvariants has not been well characterized in the southern parts of Africa.

Study: Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa. Image Credit: TakSato / Shutterstock.com

Study: Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa. Image Credit: TakSato / Shutterstock.com

About the study

In the present study, researchers quantitatively assessed alterations in the immunological landscape of SARS-CoV-2 over time. The researchers were particularly interested in the period of BA.1/2 dominance, wherein they compared the epidemiologic properties of Omicron and previously circulating SARS-CoV-2 variants using data from urban and rural cohorts in South Africa.

In June 2020, the prospective household study of SARS-CoV-2, influenza, and respiratory syncytial virus community burden, transmission dynamics, and viral interaction in South Africa-COVID-19, which is otherwise known as PHIRST-C, recruited 1,200 individuals from 222 households. A total of 114 households with 643 individuals resided in rural locations, whereas the urban site included 108 households with 557 individuals.

The present analysis was performed on a subset of the PHIRST-C sample population of 905 out of 1,200 individuals. SARS-CoV-2 infections during Omicron BA.1/2 predominance were assessed based on real-time reverse transcription polymerase chain reaction (rRT-PCR) assay and serology assessments throughout mid-September 2021.

Between July 2020 and April 2022, 10 serum samples were obtained sequentially from every participant, with blood drawn every two months before, during, and after the emergence of Omicron BA.1. Patients were followed up for active SARS-CoV-2 infection between July 16, 2020, and August 28, 2021, in the rural region, and between July 27, 2020, and August 28, 2021, in the urban region during the dominance of the SARS-CoV-2 D614G, Beta, and Delta strains.

At follow-up, nasopharyngeal swabs were obtained two times each week for COVID-19 diagnosis by rRT-PCR. Cumulative SARS-CoV-2 infection and re-infection rates during BA.1/2 dominance was also assessed. Data were incorporated into a chain-binomial household transmission model adjusted for sex, age, and the two sites to assess Delta and Omicron variant characteristics.

Among the study participants, less than 20% had received one or more COVID-19 vaccine doses before Omicron emergence at the two sites. The estimated infection attack rates were compared with COVID-19 national hospital surveillance data. Infection fatality ratios (IFRs) were calculated for the COVID-19 waves in the urban site.

Study findings

BA.1/2 infection attack rates were 65% and 58% in rural and urban sites, respectively, with breakthrough infections and reinfections accounting for over 60% of cases at the two sites. The immunological landscape was fragmented with 14 distinctive categories of SARS-CoV-2 exposure during Omicron BA.1/2 predominance.

Study participants had more than two-fold higher odds of BA.1/2 infections than Delta infections, with an odds ratio (OR) of 2.4 when Omicron was compared with Delta infections.

COVID-19 caused by the D614G, Beta, and Delta strains conferred 13%, 34%, and 51% protection against Omicron BA.1/2 infections, respectively. Hybrid immunity, which is defined as the immunity provided by both previous SARS-CoV-2 infection and COVID-19 vaccination, and repeated COVID-19 diagnoses without vaccination reduced the likelihood of BA.1/2 infection by 60% and 85%, respectively. Breakthrough infections and reinfections had a 41% reduced risk of onward SARS-CoV-2 transmission than primary SARS-CoV-2 infections with an OR of 0.6.

In the rural region, infection attack rates of 8.2%, 21%, and 39% were observed for D614G, Beta, and Delta strains, respectively, with greater rates, reported every successive COVID-19 wave. The corresponding rates in the urban region were 26%, 32%, and 23%, respectively.

Cumulative infection rates in rural and urban sites were 68% and 81%, respectively, with primary SARS-CoV-2 infections accounting for most cases at the two sites. Contrastingly, reinfections were more common during BA.1/2 dominance.

Study participants experienced 1.3 and 1.4 COVID-19 episodes in rural and urban regions, respectively, in the initial two years of the COVID-19 pandemic. The large proportion of reinfections during Omicron dominance shifted the immunological landscape towards repeated SARS-CoV-2 exposure dominance, with 52% and 60% of individuals in the rural and urban sites, respectively, reporting more than one exposure reported after the fourth wave. Reinfection to infection ratios were 2.0 and 1.4 in urban and rural sites, respectively.

The risk of SARS-CoV-2 household transmission is significantly reduced with household size. Children younger than four years of age were more susceptible to household SARS-CoV-2 transmission as compared to 35- to 49-year-old adults. ORs for the urban and rural sites were 2.2 and 4.1, respectively.

Cumulative SARS-CoV-2 incidence rates reported by the surveillance system for Omicron were 0.8 and 0.5 for every 100 persons in the urban and rural sites, respectively, with corresponding infection ascertainment rates of 0.8% and 1.3%, respectively. The estimated IFR was 0.04% during BA.1/2 dominance, which was significantly less than that which was reported in the previous three waves.


The study findings demonstrate that Omicron BA.1/2 displayed a heterogeneous immune landscape, with subgroups of populations characterized by distinctive histories of SARS-CoV-2 exposure in South Africa.

*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:
Pooja Toshniwal Paharia

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Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.


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