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Vinod Scaria
The Omicron variant of concern which was initially identified by researchers in South Africa late last year and rapidly spread across the world. SARS-CoV-2 being an RNA virus, evolves by accumulating genetic mutations, and these are introduced during the process of infection and replication of the virus. It is therefore important to note that continued transmission of the virus would significantly enrich the evolutionary landscape of the virus through accumulation of genetic mutations.
A number of omicron sublineages, with additional mutations have now been reported from across the world. Of these, a subset of lineages have shown significant and rapid rise in numbers in different geographies. In the early days of omicron, the lineage diverged to BA.1 and BA.2 and the latter predominated the spread across the world.
One of the approaches to compare and contrast a lineage with respect to another, is to calculate the growth advantage. BA.2.12 and BA.2.12.1 are two lineages of Omicron which have shown significant growth advantage with respect to Omicron (BA.2) lineage in the United States. Apart from the United States, the lineage has also shown growth in Canada and the United Kingdom. The BA.2.12.1 has additional spike mutations S704L and L452Q while BA.2.12 has only additional S704L on the BA.2 background. Mutations in the L452 position of the spike protein , which is part of the receptor binding domain (RBD) have been previously reported in a number of other variants, including Delta Epsilon and Lambda. A similar mutation L452R mutation is also seen in BA.4 and BA.5 lineages, presently increasing in numbers in South Africa. The S704L and L452Q mutations are unlikely to be the end of evolution of the lineage, as evidence suggests that additional mutations including A879V have been accumulating in some sequences from the United States of America , as the lineage explores the fitness landscape.
Spike protein mutations in the BA.2.12.* lineages of SARS-CoV-2. The mutations S704L and L452Q are marked. Image credits - Mercy Rophina
The growth advantage of a lineage of the virus in comparison with other lineages could largely be due to advantages in transmission or due to the immune escape or in other words, the ability of a lineage to infect people who have been previously immunised - either by infections or by vaccination. These infections are also called re-infections and breakthrough infections respectively.
It is not absolutely clear how the L452Q mutation confers the growth advantage in BA.2.12.1. Previous studies from Jesse Bloom Lab do not suggest mutations in the L452Q to be significantly involved with the ability of the virus to evade antibodies. The L452 position of the spike protein is critical for binding to the human receptors and therefore it is indeed likely that the L452Q mutation could potentially enhance the transmissibility of the virus.
While the largest number of sequences of BA.2.12.1 has come from the United States of America, many other countries in Europe has reported BA.2.12.1 lineage - including Canada, United Kingdom, Australia, Germany and Israel . Much recently, the variant has been reported in India, as suggested by news sources quoting the National Centre for Diseases Control. New Delhi. Whether the lineage is associated with severity of COVID-19 is not much known at this point in time.
While studies are ongoing to ascertain the biological significance of the mutations and how it could impact immune escape and binding to the host receptors, apart from the clinical outcomes of the infections, it is possibly the best time to pull up your masks, protect the elderly and with comorbidities with precautionary doses of vaccine if eligible. We should always keep in mind that stopping the virus from mutating is entirely dependent on our ability to stop the transmission of the virus.
The Omicron variant of concern which was initially identified by researchers in South Africa late last year and rapidly spread across the world. SARS-CoV-2 being an RNA virus, evolves by accumulating genetic mutations, and these are introduced during the process of infection and replication of the virus. It is therefore important to note that continued transmission of the virus would significantly enrich the evolutionary landscape of the virus through accumulation of genetic mutations.
A number of omicron sublineages, with additional mutations have now been reported from across the world. Of these, a subset of lineages have shown significant and rapid rise in numbers in different geographies. In the early days of omicron, the lineage diverged to BA.1 and BA.2 and the latter predominated the spread across the world.
One of the approaches to compare and contrast a lineage with respect to another, is to calculate the growth advantage. BA.2.12 and BA.2.12.1 are two lineages of Omicron which have shown significant growth advantage with respect to Omicron (BA.2) lineage in the United States. Apart from the United States, the lineage has also shown growth in Canada and the United Kingdom. The BA.2.12.1 has additional spike mutations S704L and L452Q while BA.2.12 has only additional S704L on the BA.2 background. Mutations in the L452 position of the spike protein , which is part of the receptor binding domain (RBD) have been previously reported in a number of other variants, including Delta Epsilon and Lambda. A similar mutation L452R mutation is also seen in BA.4 and BA.5 lineages, presently increasing in numbers in South Africa. The S704L and L452Q mutations are unlikely to be the end of evolution of the lineage, as evidence suggests that additional mutations including A879V have been accumulating in some sequences from the United States of America , as the lineage explores the fitness landscape.
Spike protein mutations in the BA.2.12.* lineages of SARS-CoV-2. The mutations S704L and L452Q are marked. Image credits - Mercy Rophina
The growth advantage of a lineage of the virus in comparison with other lineages could largely be due to advantages in transmission or due to the immune escape or in other words, the ability of a lineage to infect people who have been previously immunised - either by infections or by vaccination. These infections are also called re-infections and breakthrough infections respectively.
It is not absolutely clear how the L452Q mutation confers the growth advantage in BA.2.12.1. Previous studies from Jesse Bloom Lab do not suggest mutations in the L452Q to be significantly involved with the ability of the virus to evade antibodies. The L452 position of the spike protein is critical for binding to the human receptors and therefore it is indeed likely that the L452Q mutation could potentially enhance the transmissibility of the virus.
While the largest number of sequences of BA.2.12.1 has come from the United States of America, many other countries in Europe has reported BA.2.12.1 lineage - including Canada, United Kingdom, Australia, Germany and Israel . Much recently, the variant has been reported in India, as suggested by news sources quoting the National Centre for Diseases Control. New Delhi. Whether the lineage is associated with severity of COVID-19 is not much known at this point in time.
While studies are ongoing to ascertain the biological significance of the mutations and how it could impact immune escape and binding to the host receptors, apart from the clinical outcomes of the infections, it is possibly the best time to pull up your masks, protect the elderly and with comorbidities with precautionary doses of vaccine if eligible. We should always keep in mind that stopping the virus from mutating is entirely dependent on our ability to stop the transmission of the virus.
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About the author
Vinod Scaria is a scientist at the CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB). All opinions expressed are personal and do not reflect the opinion of their employers or organizations associated. He can be reached at @vinodscaria on Twitter
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