Divya Tej Sowpati

Fig: The genome maps of various lineages of SARS-CoV-2 from India

(courtesy: https://outbreak.info)
 

The ongoing second wave of COVID-19 in India has far outstripped the misery of infections and deaths seen last year. In an effort to understand the evolution of the virus, how it mutates, and if new variants of SARS-CoV-2 are emerging, India has been sequencing the virus from various COVID19 positive samples. Last month, the Indian government announced the presence of a new variant, which was colloquially though incorrectly dubbed the “double mutant”, in MH and other states and flagged its increasing frequency. Very recently, newspapers and media both from India and elsewhere, again incorrectly, have reported about a “triple mutant” in West Bengal that is supposedly “deadlier”. This write-up is a factual summary about the circulating SARS-CoV-2 variants in India in an effort to dispel the myths, and explain why their colloquial names are incorrect and misleading.

In addition to the variants of concern that were first identified elsewhere in the world such as B.1.1.7 (identified in the UK), B.1.351 (identified in SA), P.1 (identified in Brazil), there are at present two major lineages of concern circulating in India:

1. B.1.617 (“double mutant”): First sampled in early October 2020 from the state of Maharashtra, this lineage is characterized by about 15 mutations all over its genome. 6 out of the 15 mutations are present in its Spike protein, out of which two mutations, in particular, were of interest: L452R and E484Q. These were of interest because L452R was seen in a variant circulating in California, and was shown to increase the infectivity of the virus, and E484Q was shown in in vitro experiments to be an immune escape mutation (possesses the ability to bypass host immunity, either acquired by previous SARS-CoV-2 infection or conferred by vaccination). Because these two mutations were repeatedly mentioned when talking about this lineage, the colloquial name of “double mutant” came about.
2. B.1.618 (“Bengal variant”): First sampled in WB in late Oct 2020, it is a completely different lineage and has nothing to do with B.1.617. The only mutations shared by both the lineages are a few that appeared early in the pandemic such as the D614G and P314L, which are now present in almost all SARS-CoV-2 strains in circulation. Genomes of the lineage B.1.618 are being reported in increasing numbers from West Bengal. This lineage is characterized by the Spike mutation E484K and two amino acid deletions in Spike: Y145 and H146. Both of these changes have earlier been reported to be associated with immune escape. In particular, the mutation E484K was also seen earlier in lineages B.1.351 and P.1, and is associated with the outbreaks in SA and Brazil respectively. There were also reports from Brazil that the P.1 is found in growing proportions in WB, and has the Spike del145-146 as well as E484K, both of which are known immune escape mutations. E484K, in particular, was seen before in both B.1.351 and P.1 lineages and were associated with outbreaks in SA and Brazil respectively. The P.1 lineage was also shown in few reinfection cases in Brazil, further suggesting that the mutation E484K is enabling SARS-CoV-2 to escape immunity better. Whether this behavior of the virus will also be seen in the B.1.618 lineage remains to be determined.

So what’s the “triple mutant” then?

The strain which various news articles and others are referring to as “triple mutant” is a sub-lineage of B.1.617, with an extra mutation in its Spike protein: V382L. The mutation V382L has previously been reported in the US as a low-frequency mutation with possible immune escape properties as seen in in vitro assays.

So why can’t we use the names “double”/”triple” mutants?

Because such names are scientifically inaccurate and wrongly imply that there are only two or three mutations in these lineages. As mentioned above, each of these lineages carry >15 mutations each. In fact, given the rate of SARS-CoV-2 evolution (~22 mutations per year), all current circulating variants carry on an average 20 mutations or more when compared to the original Wuhan strain which was sequenced in January 2020. Also, the number of mutations in a lineage has no connection to the behavior of a variant. A year from now, most of the variants will have close to 40 mutations each, because that is part of the natural evolution of the virus.

In conclusion, it is incorrect to call the current circulating variants in India as “double” or “triple” mutants. It is also incorrect that the lineage seen in West Bengal is the “triple” mutant. This is why scientists use a specific nomenclature to refer to these strains, such as B.1.617 and B.1.618. Also, there is no conclusive evidence at this point that associates any of these lineages with a more severe or lethal outcome of COVID19.

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Dr. Divya Tej Sowpati is a scientist at CSIR-Center for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad.

Good idea