What newly-discovered C.1.2 lineage of SARS-CoV-2 is & why it’s not yet a ‘variant of concern’

C.1.2 variant is not as widespread as other Covid variants of concern. Just 107 samples of the variant have been isolated across the world and 95 of them are from South Africa.

A nurse fills a syringe with a dose of the Pfizer-BioNTech Covid-19 vaccine | Photographer: SeongJoon Cho | Bloomberg

New Delhi: C.1.2 — a new SARS-CoV-2 variant identified in South Africa — has raised new concerns regarding the Covid-19 pandemic after researchers from the country reported that the variant had mutations of concern.

So far, just 107 samples of the variant have been isolated across the world and 95 of them are from South Africa.

Other countries to have reported this sample include Mauritius, Zimbabwe, Botswana, China, New Zealand, Portugal, Switzerland and UK. The variant has not yet been found in India.

American epidemiologist Maria Van Kerkhove, who is WHO’s Covid-19 Technical Lead, said that WHO has regularly been discussing with South African researchers about their work on sequencing throughout the pandemic.

“To date there are ~100 sequences of C.1.2 reported globally, the earliest reports from May ‘21 (from South Africa),” Kerkhove tweeted Monday.

“At this time, C.1.2 does not appear to be (rising) in circulation, but we need more sequencing to be conducted & shared globally. Delta appears dominant from available sequences,” she added.

C.1.2 not as widespread as other variants

Unlike some of the previous variants like Alpha, Beta and Delta, C.1.2 is yet to be classified as a variant of interest or a variant of concern.

WHO classifies SARS-CoV-2 variants based on their properties such as indications of increased transmissibility or ability to cause severe disease.

A ‘variant of concern’ has demonstrated to be associated with one or more of the following changes at a degree of global public health significance — increase in transmissibility, increase in virulence or change in clinical disease presentation, decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics.

For example, the Delta variant has been classified as ‘variant of concern’ as studies indicate that it causes severe disease.

The Alpha variant, meanwhile, has been found to be more easily transmissible, which has also made it a variant of concern.

Kappa, Eta, Iota and Lambda are some examples of variants of interest. Variant of interest, according to the WHO, is a variant with genetic changes that are predicted or known to affect virus characteristics such as transmissibility, disease severity, immune escape, diagnostic or therapeutic escape.

Such variants may also be identified to cause significant community transmission or multiple Covid-19 clusters, in multiple countries with increasing relative prevalence alongside increasing number of cases over time or other apparent epidemiological impacts to suggest an emerging risk to global public health.

However, the C.1.2 is not yet that widespread.

Mutations of concern

However, C.1.2 does share many of the same genetic mutations that have been seen in variants of concern.

The variant has 14 mutations in spike protein, which facilitates the entry of the virus into the host cell. Mutations in the spike protein are more concerning because most vaccines are designed to mimic the spike protein of the original variant of the virus.

For example, E484K and N501Y mutations in the spike protein reported in this variant have been previously found in three of the four variants of concern (Alpha, Beta and Gamma).

Research has shown that the E484K mutation in the spike protein increases the virus’ ability to bind with the ACE2 receptor — an enzyme attached to the membrane of cells that facilitates the entry of the SARS-CoV-2 virus.

Similarly, the N501Y has been associated with increased transmission of the virus.

The researchers from South Africa also pointed out additional mutations — C136F, Y449H and N679K — in the variant, which they said are also likely to impact the ability of antibodies to fight off the virus and also increase the replication of virus.

C.1.2 lineage has higher mutation rate than other variants

The researchers also noted that the rate of mutation in this variant is higher than usual.

According to the team, the overall rate of evolution of SARS-CoV-2 in 2020 was about 24 substitutions per year. In comparison, the current global estimate, which includes all variants of concern or interest, has a similar rate of approximately 25.2 substitutions per year.

Rate of substitutions describes the frequency of new mutations in a single gene or organism over time.

However, the C.1.2 lineage emerged from a mutation rate that is about 41.8 mutations per year, which is approximately 1.7 times faster than the current global rate and 1.8 times faster than the initial estimate of SARS-CoV-2 evolution.

However, Vinod Scaria, a scientist at the CSIR Institute of Genomics and Integrative Biology and one of the leading experts of genomic studies in India, told ThePrint that this is not unusual in a newly emerging variant.

“Brief and early spurts in rates of substitutions are observed in VoCs (variants of concern) as well as early outbreaks for non-VoCs,” said Scaria. He added that once the variant becomes more widespread, this substitution rate goes down.

In a blog post, published Wednesday, Scaria wrote, “At this point in time, we do not know whether the variant is more transmissible or causes immune escape from the available data, though the mutations have been independently associated with these properties. Research is underway to better characterize and understand the properties of the virus.”