FREQUENTLY ASKED QUESTIONS: C.1.2 COVID-19 LINEAGE

C.1.2 is a new lineage (or version) of the SARS-CoV-2 virus.

SARS-CoV-2 like all viruses mutates/changes continually and randomly. When a mutation offers some benefit, for example, enabling the virus to replicate better or evade immune responses in humans, the mutation is passed on as the virus multiplies. This mutated virus is then transmitted to another person. The C.1 lineage was detected during our first wave of infections in South Africa and now in the third wave has accumulated additional mutations and evolved into the C.1.2 lineage.

A VOI is a variant of interest and a VOC is a variant of concern. These are classifications for different variants of SARS-CoV-2. A variant of interest is one that has spread significantly within a region or globally and has some mutations that might alter transmissibility, pathogenesis, immune resistance or the epidemiology of the virus. A variant of interest becomes a variant of concern when it has been proven to have changes in transmissibility, pathogenesis, immune resistance or epidemiology. To date, the C.1.2 lineage is neither a VOI nor a VOC.

The Network for Genomic Surveillance in South Africa routinely collects samples from people that have tested positive for SARS-CoV-2 throughout the country and sequences the virus within these samples to monitor viral mutations. We then compare these sequences to ones we have seen before, like a game of spot the difference. If we see differences, we take note of where these differences are and whether they are likely to alter the function of the virus or our immune responses to the virus.

C.1.2 was first detected in South Africa in May 2021 but has been seen sporadically in nine other countries (Botswana, Zimbabwe, the Democratic Republic of the Congo, Mauritius, New Zealand, Portugal, China, Switzerland and England).

It is not yet clear whether C.1.2 is more transmissible. The variant shares mutations with other variants and some mutations have been linked to increased transmission. Although the variant was detected in May, the levels remain low and the NICD continues to monitor the variant and its spread.

Variants are assigned a Greek name when it is classified as a variant of concern (VOC) or a variant of interest (VOI). Variants with mutations that are predicted to impact function are classified as a VOI once that variant has spread either significantly in an area or globally. A VOI becomes a VOC when the effect of the mutations on function has been proven to be detrimental. Due to the low frequency of C.1.2 and lack of data to explain the effect of the mutations in this lineage, it does not meet the criteria to be classified as a VOI or VOC.

There are 114 C.1.2 genomes from South Africa in GISAID (the global reference database for SARS-CoV-2 viruses, www.gisaid.org). However, these only account for ~2.5% of the viruses circulating in South Africa right now, with the majority being Delta.

It is a variant, meaning a different “version” of the virus; however, the “potential” refers to its potential to eventually either be classified as a VOC/VOI. It shares mutations with VOCs that have a functional impact as well as additional mutations that we are currently studying. So although it is a variant, it is not yet a VOC/VOI, but it has the potential to become one.

Viruses randomly mutate all the time; mostly these do not have a great effect on function, but sometimes these mutations give the virus an added benefit. Therefore, the identification of many mutations does not necessarily mean a “worse” virus.

One reason we expect that the vaccines will work, despite the mutations in C.1.2, is because we are familiar with several of these mutations. We have extensive data from the other variants, like Beta and Delta, showing the effect of these mutations. Because of this, we can to some extent predict the effect of those mutations, even in the context of C.1.2.

Another reason is that the T cell arm of the immune system in part mediates protection from severe disease, which is separate from the antibodies. T cells are much more tolerant of mutations and there is data from laboratories across the world that although there might be a reduction in the ability of antibodies to bind to these viruses, T cells (which are the cells that protect you from severe disease) maintain their activity against the currently circulating variants.

C.1.2 is present at a low frequency and is gaining traction slightly, which is why we are tracking and watching it carefully. It is to some extent doing what Delta did at the beginning of the second wave. However, at this stage, it is impossible to predict what variants are going to do.

We cannot conclusively say that the C.1.2 lineage is dominant in any of the provinces, purely because our sequencing efforts are not equal across all the provinces. The most number of C.1.2 sequences are from Gauteng, but we also have the most number of sequences from Gauteng province.  

We have defined the impact of mutations in current VOIs or VOCs because they have been in circulation for some time and have infected a significant number of individuals. We have been able to pinpoint the detrimental impact of individual and combined mutations in these VOIs or VOCs. Therefore, when we see emerging lineages with similar mutations, we take notice because we expect a detrimental impact.

The C.1.2 lineage has to be present in a significant amount of sequences for a sustained period in order for it to be recognised as a VOI by the World Health Organization. If it is classified as a VOI, further studies showing that the lineage alters viral pathogenesis, immune resistance, transmissibility and epidemiology are needed before it can be classified as a VOC.

There is no need to review lockdown restrictions at this time. All the regulations that are required in terms of managing this current third wave/resurgence are in place, regardless of the variant. Adherence to non-pharmaceutical interventions remain critical and individuals who qualify for vaccination are encouraged to do so.

The Network for Genomic Surveillance in South Africa continuously and rigorously monitors the emergence of new SARS-CoV-2 variants in South Africa and globally. This continual monitoring we hope will enable us as a country to be better prepared to respond if further public health action is warranted. Because C.1.2 has been detected throughout South Africa as well as other countries we intended to inform other scientists and authorities including the WHO and South African NDoH to enable others to be on the lookout as well. However, it is important to note that we will likely continue to identify different variants and the public should really only be concerned when these variants are classified as either a VOI or VOC.

It certainly has more mutations than the currently described VOI/VOCs we have seen circulating globally. C.1.2 has on average 30 mutations across its entire genome, which is quite mutated when you compare it to other VOC/VOIs, which have on average 18 mutations.

Out of the 127 C.1.2 sequences currently on GISAID, 114 are from South Africa. C.1.2 has generally only been detected in one or two sequences from other countries. We have been sequencing genomes extensively throughout South Africa. Additionally, in comparison to the UK for example, we are doing relatively light genomic surveillance, yet we have detected many more C.1.2 sequences than any other country. Further to this, the genomic data shows that C.1.2 evolved from a precursor lineage (called C.1) that was predominant in South Africa in the first wave.

We have raised awareness of this particular variant because of its mutation profile and its sustained spread throughout South Africa. It has many mutations that are shared with other VOI/VOCs as well as additional mutations within regions that might affect its function.

Many variants are circulating globally and will continue to circulate unless we can get a high enough coverage of vaccination in South Africa and globally. Our raising the awareness of C.1.2 has been to inform others to be on the lookout for this lineage. However, right now there is no reason to expect that it would be any different to any other VOC/VOI currently circulating.

This is indeed a very difficult balancing act. It is imperative for us to do this type of monitoring so that we would be able to detect new variants that might pose a threat very early on to get ahead of the virus in some ways. It is important to note that new variants are not unique to South Africa. Of the nine VOC/VOIs that are listed by the WHO, only one was first detected in South Africa. This is a global phenomenon and is crucial for everyone to continue to monitor. Since we and others across the globe will continually detect these variants one should only be concerned when they reach the status of VOC. Right now C.1.2 is only a variant under investigation (VUI) which means it is being monitored but does not meet the criteria for either VOI/VOC.

Yes, the majority of the sequences assigned to C.1.2 come from South Africa. We think it originated here having evolved from C.1, which was one of the viruses that predominated our first wave of infections with limited spread globally.