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SARS-CoV-2 Genome Sequencing Study Identifies 16 Viral Lineages in South Africa

NEW YORK – An international team led by researchers at the University of KwaZulu-Natal in Durban, South Africa has identified 16 new lineages of SARS-CoV-2 that were isolated from South Africans between March 6 and Aug. 26, 2020, most of which have unique mutations that have not been identified elsewhere.

In a paper published on Tuesday in Nature Medicine, the researchers said that their analysis of 1,365 near whole genomes also showed that three viral lineages (B.1.1.54, B.1.1.56, and C.1) spread widely in South Africa during the first wave of the COVID-19 pandemic, comprising about 42 percent of all infections in the country at the time. The newly identified C lineage of SARS-CoV-2, C.1, has 16 mutations compared to the original Wuhan virus sequence, including one amino acid change on the spike protein. This lineage was the most geographically widespread in South Africa by the end of August 2020, while an early South African-specific lineage called B.1.106 became extinct after nosocomial outbreaks were controlled in KwaZulu-Natal Province, the researchers said.

"Our findings show that genomic surveillance can be implemented on a large scale in Africa to identify new lineages and inform measures to control the spread of SARS-CoV-2," the authors wrote. "Such genomic surveillance presented in this study has been shown to be crucial in the identification of the 501Y.V2 variant in South Africa in December 2020."

The South African viral genomes in this study were assigned to 42 different lineages based on the proposed dynamic nomenclature for SARS-CoV-2 lineages, the researchers said. This included 16 South Africa-specific lineages, defined as being lineages that were predominant in South Africa as of Sept. 15, 2020. The investigators focused on the three largest monophyletic lineage clusters (C.1, B.1.1.54, and B.1.1.56) that spread in South Africa during lockdown and then grew into large transmission clusters during the peak infection phase of the country's epidemic.

The data they collected suggests that the fast spread of the three lineages was likely a result of localized outbreaks and expected transmission dynamics, rather than caused by any fitness advantage the viral lineages may have had. For example, the researchers determined that lineage C.1 most likely emerged in early May 2020 in Johannesburg, in Gauteng Province, where it quickly spread to the adjacent North West Province, causing a large nosocomial outbreak. From there, it spread through two independent events to the northern province of Limpopo, then to KwaZulu-Natal, and to the adjacent Free State Province.

The researchers also analyzed the sequences of the three main lineage clusters to determine their lineage-defining mutations. They found that, on average, sequences in the C.1 cluster accumulated roughly 16 mutations, whereas B.1.1.56 and B.1.1.54 had approximately 13 to 14 mutations relative to the Wuhan lineage. This was also higher than the number of acquired mutations in other sequences as of Aug. 26.

Further, they found that hospital outbreaks were major contributors to lineage distribution in South Africa. For example, lineage C.1 was amplified in a nosocomial outbreak in the North West Province in April 2020 before spreading to KwaZulu-Natal and other provinces. B.1.106 also emerged in a nosocomial outbreak in KwaZulu-Natal in April that infected 88 healthcare staff and 47 patients, and dominated most of the early infections in Durban.

Importantly, the researchers said, the data showed that several SARS-CoV-2 lineages, each with their own unique mutations, emerged within localized epidemics during South Africa's lockdown period, even as the introduction of new lineages from outside South Africa was being curbed. Because many of the mutations in the analysis are synonymous, this argues against selection for fitter variants, which contrasts with reported characteristics of variant 501Y.V2, known colloquially as "the South African variant," the researchers said.

All four of these lineages — C.1, B.1.1.54, B.1.1.56, and 501Y.V2 — contain the D614G mutation in the spike gene, they also noted. Although they are currently investigating any fitness cost associated with the different lineages, they found only three other non-synonymous mutations in the spike gene, which suggests that the evolutionary stability of SARS-CoV-2 was maintained in South Africa during the first wave of the pandemic.

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