SEEMA clears some doubts about the different variants of the virus that has hit the country
India’s second wave of Covid-19 has hit the country badly. On average, about 350,000 new cases are being added and 2,000 – 3,000 official deaths are being recorded daily.
There are several reasons attributed for this second wave, chief among them the new Sars-Cov2 variants dubbed ‘double’ and ‘triple’ mutants. These terms are scientifically incorrect but we will use them for the sake of simplicity.
But first, what are mutations? All viruses mutate naturally as they replicate. A mutation is a change in the DNA that changes the amino acid sequence of the viral protein. For eg. in the mutation L452R, the spike protein of the coronavirus has one amino acid L (leucine) in the original virus at the 452nd position has changed to R (arginine).
Most spike mutations make either no difference or make spike unable to bind to cells. But a few rare ones make the virus more infectious. Multiple mutations could result in a variant of the virus the body finds harder to fight.
The ‘double mutant,’ termed B.1.617, actually has more than 15 mutations but got its name from two main mutations in the spike protein: L452R and E484Q.
The B.1.617 variant, first reported in India last October, has been found in 61% of samples sequenced in Maharashtra, the state that recorded the maximum number of cases in the second wave in India. This variant has been found in at least 10 countries, including the U.S.
The World Health Organization, dubbed the B.1.617 double mutant variant as a ‘variant of interest’ because it is suspected to be more infectious than the original strain and may have ‘immune escape’ properties – the ability to dodge the defenses the body may have set up against another strain.
WHO has classified variants as ‘variant of interest,’ ‘variant of concern’ and ‘variant of consequence’ based on the evidence for increased transmission, heightened severity of the disease, or reduced neutralization by vaccines or antibodies.
A study published recently has shown that Covaxin, India’s first coronavirus vaccine, works against the double mutant, and preliminary results suggest that Covishield, the Oxford-AstraZeneca product, also protects against this variant.
The ‘triple mutant’ is a spin-off mutant from the double mutant, B.1.617. In addition to the two main mutations, L452R and E484Q, it has another mutation, V382L, in the spike protein. This has been seen mainly in Maharashtra state.
Divya Tej Sowpati, a scientist at the Centre for Cellular and Molecular Biology, Hyderabad, India, said, “The mutation V382L in the spike was shown to be a potential immune escape mutant in some in vitro [outside the body] studies. However, no evidence exists in real cases that it might be bypassing immunity.”
He added, “It (the mutation) appeared in the U.S. a while ago (independently, not along with L452R and E484Q), and continued to stay in low frequencies.”
So V382L is just a mutation of interest at this point.
Then there is the ‘Bengal’ variant, B.1.618, found in several samples in the state of West Bengal. It has the mutation E484K in the spike. This variant has been mistakenly reported as the triple mutant as both the variants appeared at the same time.
Sowpati explained, “The ‘Bengal variant’ is an independent lineage compared to B.1.617 (the parent lineage for the ‘triple’ mutant). Other than a couple of mutations, they don’t share any other genetic signatures, which is the main basis for categorizing variants/lineages.”
The E484K mutation is present in several lineages, including the South African (B.1.351), Brazilian (B.1.1.28) and some UK variants. It is suspected to be highly transmissible and escape immunity.
Sowpati added that based on current data, the Bengal variant, although present in good numbers in West Bengal, has not surpassed the double mutant. Similarly, the triple mutant is a very small proportion of B.1.617 sequenced so far. “Of course, new data from current and further samples may change this perspective, but at least at present I don’t think there is any evidence for saying either Bengal or triple mutant is more infectious than double mutant,” he said.
Collecting data through gene sequencing of variants is crucial to managing the pandemic. This January, India set up the Indian SARS-CoV2 Genomics Consortium (INSACOG), a network of 10 laboratories, to sequence the virus and its variants.
Sowpati said, “Staying aware of potential harmful variants can help policies restrict the spread of such variants both within and across countries. Other than that, if we come across variants that are escaping immunity conferred by vaccines, having their sequences helps us design better and more efficient vaccines.”
It is also important to keep track of mutations that may potentially escape diagnosis through current RT-PCR kits, he said. “If we ever detect such a variant, we can immediately redesign kits that use a different target region.”
Viruses mutate when they spread and replicate. Thus, the more they get to multiply, the more chances of new variants popping up. So containing the spread by masking up, maintaining physical distance and hygiene are important.
