The National Institute for Communicable Diseases in South Africa stated that the new variant — C.1.2 — was first detected in May and has now spread to “the majority of the provinces in South Africa and in seven other countries spanning Africa, Europe, Asia and Oceania”.
The variant has drawn the attention of scientists because of the rapid rate at which it is changing and the mutations within its genome which are similar to those seen in many variants of concern and variants of interest, including the Delta.
Where was the C.1.2 variant first detected?
According to a pre-print study which has not been peer-reviewed yet, the C.1.2 variant was first detected in the Mpumalanga and Gauteng provinces of South Africa in May this year. In June, it was also detected in the KwaZulu-Natal and Limpopo provinces of South Africa as well as in England and China.
The paper states that as of August 13, the C.1.2 variant has been detected in six South African provinces (including the Eastern Cape and Western Cape), the Democratic Republic of the Congo, Mauritius, New Zealand, Portugal and Switzerland.
What is unique about this variant?
The study found that C.1.2 has “mutated substantially” in comparison to C.1 variant, which was one of the dominant lineages during the spike in infections during the first wave in South Africa.
What sets the C.1.2 variant apart from other Covid-19 strains is the speed at which it has been mutating.
The study found that C.1.2 is undergoing 41.8 mutations per year, which is “approximately 1.7-fold faster than the current global rate and 1.8-fold faster than the initial estimate of SARS-CoV-2 evolution”.
Global detection of C.1.2 sequences (Source: http://www.medrxiv.org)
This is one of the reasons why scientists are keenly observing the C.1.2 variant now because, as the study states, this “short period of increased evolution compared to the overall viral evolutionary rate was also associated with the emergence of the Alpha, Beta and Gamma” variants.
The study also found that there were consistent increases in the number of C.1.2 genomes in South Africa each month, rising from 0.2 per cent of the genomes sequenced in May to 1.6 per cent in June and then to 2 per cent in July.
The study further states, “C.1.2 has accumulated a number of substitutions beyond what would be expected from the background SARS-CoV-2 evolutionary rate. This suggests the likelihood that these mutations arose during a period of accelerated evolution in a single individual with prolonged viral infection through virus-host co-evolution.”
Full C.1.2 genome representation (Source: http://www.medrxiv.org)
What are the key mutations that the C.1.2 carries?
Scientists have found that C.1.2 carries some of the mutations that were previously seen in the C.1 variant. But it has picked up additional mutations within the ORF1ab, spike, ORF3a, ORF9b, E, M and N proteins.
Several of the spike mutations identified in C.1.2 were previously seen in other variants of concern or variants of interest.
Dr Kerkhove also stated that as of now, WHO has not characterized C.1.2 as a variant of concern or a variant of interest.
For instance, the D614G mutation is common to all these variants, E484K and N501Y mutations are present in Beta and Gamma, E484K was also seen in Eta, and N501Y in Alpha. Moreover, the T478K mutation which was seen in some of the C.1.2 variants is also found in Delta.
Thus, C.1.2 contains many mutations that have been identified in all four VOCs (Alpha, Beta, Delta and Gamma) and three VOIs (Kappa, Eta and Lambda). It also has key additional mutations like Y449H at its receptor-binding domain and N679K adjacent to its furin cleavage site.
(Source: http://www.medrxiv.org)
Will Covid-19 vaccines work against this variant?
The study has found that some of the mutations that the C.1.2 variant carries may make it better at evading immune response.
Moreover, many of the mutations have been associated with improved ACE2 binding and reduced neutralisation by antibodies.
But the study stated that the exact impact of this variant on neutralisation of antibodies due to Covid-19 infection or vaccination is still being assessed.
The National Institute for Communicable Diseases in a release later stated, “We are being cautious about the implications, while we gather more data to understand virus of this lineage…Based on our understanding of the mutations in this variant, we suspect that it might be able to partially evade the immune response, but despite this, that vaccines will still offer high levels of protection against hospitalization and death.”
Introduction of C.1.2. spike mutations (Source: http://www.medrxiv.org)
So, is there enough cause for concern?
Dr Maria Van Kerkhove, the technical lead of WHO, has said that 100 sequences of C.1.2 have been reported globally till now and currently it does not appear to be “increasing in circulation”.
“The WHO has regularly been discussing with South African researchers their work on sequencing throughout the COVID-19 pandemic. We are grateful for researchers in South Africa who first presented their findings on variant C.1.2 to the WHO Virus Evolution Working Group in July ’21,” she tweeted.
She added, “At this time, C.1.2 does not appear to be Upwards arrow in circulation, but we need more sequencing to be conducted & shared globally. Delta appears dominant from available sequences.”
A virologist and lecturer in immunology and infectious diseases with the University of Sydney’s Central Clinical School, Dr Megan Steain, told the Guardian that scientists are on alert because of the mutations that the C.1.2 variant carries.
Steain said, “It contains quite a few key mutations that we see in other variants that have gone on to become variants of interest or concern. Any time we see those particular mutations come up, we’d like to keep an eye on the variant to see what it’s going to do…C.1.2 would have to be pretty good, pretty fit, and pretty fast to outcompete Delta at this stage. I think we’re still very much at a point where this could die out, the prevalence is really low.”
So far, the variant has not been able to outcompete the other dominant Covid strains in the countries in which it has spread. For instance, C.1.2 accounted for three per cent of positive Covid samples in South Africa in July. In the same month, Delta accounted for 89 per cent of the positive samples in the country.
But the emergence of a new Covid-19 strain which is mutating at a rapid rate can be a reminder of the challenges that lie ahead due to emerging variants.
Richard Lessells, one of the authors of the South African report on C.1.2, told Reuters that the emergence of C.1.2 is a clear sign that the “pandemic is far from over and that this virus is still exploring ways to potentially get better at infecting us”.
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Young boys with their pet dogs make their way down a busy street in the Diepsloot Township, north of Johannesburg, Thursday, Aug. 26, 2021. (AP Photo: Denis Farrell, File) 
Global detection of C.1.2 sequences (Source: 
Full C.1.2 genome representation (Source: 
(Source: 
Introduction of C.1.2. spike mutations (Source: 
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