The Hindu Explains | Will the ‘double mutant’ novel coronavirus strain found in India lead to a further rise in infections?

Updated - March 28, 2021 11:50 am IST

The story so far: The National Centre for Disease Control (NCDC), a unit of the Ministry of Health and Family Welfare, reported this week that a unique “double mutant” variant of the novel coronavirus had been found in India. It was reported in about 200 cases in Maharashtra, and some in Delhi and Punjab. The NCDC also said about 771 cases of variants of concern (VOCs) were detected in over 10,000 samples shared by States and Union Territories.

When did mutations start emerging?

The emergence of new mutations in the novel coronavirus is par for the course. Variants pique scientific interest when scientists sequence the genomes of the virus sourced from RT-PCR-positive samples from a diverse population and compare changes in the genetic structure to the original strains from the beginning of the COVID-19 pandemic. Often, there are changes in the genetic alphabet that appear to give the virus a better evolutionary advantage in being able to continue spreading in the population. Some of these changes confer a massive advantage and become the dominant variant. Thus, a mutation called D614G in the early stages of the pandemic emerged last year, involving aspartic acid (D) in the 614th position of the amino acid being replaced with glycine (G). This gave the virus a significant advantage in gaining more efficient entry into the body. It emerged that while before March 1, 2020, only 10% of 997 global genome sequences had the mutation, 67% of sequences between March 1 and March 31 and 78% of the sequences between April 1 and May 18 had it.

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What are the existing mutant combinations?

As new variants evolve, scientists start assessing if certain combinations of mutations are more likely. A mutation N501Y last year was independently reported in South Africa and Australia, and in the United Kingdom it was correlated with a threefold spike in cases last December, where half the cases carried it. The N501Y allowed the spike protein of the virus to take hold better. The ‘UK variant’ (B.1.1.7), as it eventually came to be known, had at least 14 key mutations. However, another key mutation, E484K, which helped the virus dodge the immune system more frequently, also began to gain ground. Both these mutations together started to appear frequently in South Africa and were correlated with a large spike. That became the ‘South African’ variant, B.1.351.

These two variants, along with another called the Brazilian variant (P.1), given their spread, infectivity and ability to somewhat reduce the efficacy of vaccines are the only ones internationally termed as ‘Variants of Concern’ (VOC).

How significant is the 'double mutant' variant?

The double mutant variant reported by the NCDC has the simultaneous presence of two mutations — E484Q and L452R — that have been independently found in other variants in several countries associated with local outbreaks. The latter mutation has been individually linked to local outbreaks in California, United States, and has been shown to evade monoclonal antibodies (antibodies made in a lab with a niche targeting mechanism) produced in response to COVID-19 infection. It has also been linked to increased infectivity.

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The E484Q can escape four kinds of monoclonal antibodies and even some polyclonal antibodies derived from COVID-19 patients’ blood serum. So far, nobody knows how the combined presence of these mutations would work. About 10,787 Indian genomes have been sequenced so far and around 200 samples in Maharashtra have been found to contain the variant with the mutation, as do a handful in Delhi and Punjab.

The spike in cases — now over 60,000 a day — particularly in these States has led to speculation if it is due to mutant strains. But not enough has been done to establish that. For that, genome samples from a district or a cluster reporting a spike in cases have to be sequenced and then compared to whether a significant fraction of them has the mutations of interest.

However, experts say the U.K. variant (B.1.1.7) may be of greater concern. As of March 23, the variant had spread to a total of 125 countries across all six WHO regions and is the dominant strain in Britain. It has also been reported to have over 60% higher mortality rate, the WHO says. Earlier this week, the NCDC said about 81% of 401 samples sent for genome sequencing from Punjab were found to have the U.K. variant.

Also read | Can SARS-CoV-2 mutations undercut the efficacy of vaccines?

“This variant is more likely to contribute to an intense second wave,” Jeremy Kamil, a virologist at Louisiana State University Health Sciences Center Shreveport, told BBC recently.

What does this mean for public health?

Very little so far. As the NCDC and the Health Ministry underline, the standard prescription of wearing masks, avoiding potential super-spreading events and getting a vaccine, if eligible, remain the best defence against the virus variants.

Threatening variants emerge from the increased opportunity for the virus to replicate and reducing opportunities for this continues to be the best defence. A consortium of 10 labs in India, called the Indian SARS-CoV-2 Consortium on Genomics (INSACOG), has been sequencing a proportion of RT-PCR-positive samples and 771 have been found positive for three VOCs — the U.K., South African and Brazilian strains.

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The new variant combination in India is yet to be assigned a formal lineage name. Once that is done, there will be studies that seek to establish its frequency and association with spurts in cases. Then there will be studies that will check if the variant causes available vaccines to be less effective, or whether they are linked to severe disease. Based on what they reveal, we may have a ‘variant of concern’ uniquely associated with India.

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