Potential variant of interest in South Africa assigned to the PANGO lineage C.1.2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the ongoing coronavirus disease (COVID-19) pandemic, was first reported in 2019 in Wuhan, China. Owing to the continual evolution of the virus as it circulates among the global population, many variants have emerged.

Some of these variants, such as Alpha and Delta, have exhibited increased infectivity over the Wuhan strain. There is even some evidence to suggest that the Delta variant has exhibited immunity evasion elicited by vaccine or infection with an earlier strain.

Thus the close monitoring of emerging variants and their viral fitness has become a crucial element of pandemic management – alongside mass vaccination campaigns.

Classification of SARS-CoV-2 variants

The newly emerged variants have been classified either as variants of interest (VOI) or variants of concern (VOC) based on their clinical and epidemiological profiles. At present, among the circulating SARS-CoV-2 strains, the Alpha, Beta, Gamma, and Delta variants are categorized under VOC, while Eta, Iota, Kappa, and Lambda have been classified as VOI.

Among the VOC, Alpha, Beta, and Delta have been reported to have maximum global impact owing to their high rate of transmission and their potential to evade immune responses. Like many countries worldwide, South Africa has also been impacted by the Delta variant.

Genomic surveillance of SARS-CoV-2 strains in South Africa

Continual genomic surveillance of the SARS-CoV-2 strains in South Africa has revealed an increase in the number of sequences belonging to C.1 lineage during the third wave (May 2021) of SARS-CoV-2 infections. This observation was unexpected because C.1 was last reported in January 2021.

A team of researchers recently compared the mutational profiles between the newly identified and older C.1 sequences. They found the newly emerged sequences contained D614G mutation within the spike. Globally, C1 exhibited a minimum transmission rate. However, it was later detected in Mozambique containing additional mutations and was assigned to PANGO lineage C.1.1.

Continual genomic surveillance has resulted in the identification of more new sequences in South Africa, which are distinct from C.1.1. Scientists assigned them to the PANGO lineage C.1.2 on July 22, 2021.

This study is available in the medRxiv* preprint server, while the article undergoes peer review.

Characterization of C.1.2 lineage

C.1.2 is highly mutated compared to C.1, and all other VOC and VOI identified to date. Researchers revealed that C.1.2 is phylogenetically more close to the Lambda variant (C.37).

In May, C.1.2 lineage was detected for the first time in the Mpumalanga and Gauteng provinces of South Africa. Soon after, it was detected in many areas, such as the KwaZulu-Natal and Limpopo provinces of South Africa, as well as in England and China. By August 13, it was found in the majority of South African provinces, including the Eastern Cape and Western Cape. It was also detected in New Zealand, Mauritius, the Democratic Republic of the Congo (DRC), Portugal, and Switzerland.

The authors of this study have identified 63 sequences that matched C.1.2 lineage, among which 59 sequences were used for phylogenetic analyses and/or spike analysis. The SARS-CoV-2 genomic surveillance is ongoing, and typically a delay of around 2-4 weeks occurs between sampling and data being publicly available on Global Initiative on Sharing All Influenza Data (GISAID). Researches of the current study observed a steady increase in the number of C.1.2 genomes in South Africa.

Researchers revealed that the evolution of SARS-CoV-2 in 2020 was 8x10-4 substitutions/site/year, which is associated with 24 substitutions per year. However, the global phylogeny, including C.1.2 sequences, has shown a marginally higher clock rate of 26.6 substitutions per year. Among the majority of the sequences, the substitution rate of C.1.2 sequences is found to be much higher.

Although C.1.2 shares similar mutations with C.1, it has certain additional mutations within the ORF1ab, spike, ORF3a, ORF9b, E, M, and N proteins. Many of these mutations have occurred in the spike region. More than 50% of the viruses designated to be C.1.2 contain 14 mutations. Researchers have revealed that five of the fourteen mutations are present within the NTD, three within the receptor-binding motif (RBM), and two adjacent to the furin cleavage site. The remaining four mutations are P9L, D614G, H655Y, and T859N.

Scientists have estimated that 52% of the spike mutations detected in C.1.2 have previously been identified in other VOI and VOC. Some mutations are common between C.1.2 and other VOI and/or VOC. For example, D614G is common across all variants, E484K and N501Y mutations are found in Beta and Gamma variants, N501Y in Alpha, and E484K is found in the Eta variant.

Conclusion

The current study conducted genomic surveillance of SARS-CoV-2 during the third wave of infection in South Africa and was able to identify a new SARS-CoV-2 variant. This strain has been assigned to the PANGO lineage C.1.2, which was also detected in Europe, Asia, Africa, and Oceania. At present, the authors of this study are determining the impact of C.1.2 variant on neutralization antibody following natural infection or vaccine-induced immune response 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:
Dr. Priyom Bose

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.

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