Genome sequencing data have presented evidence of the 'double mutant' in 61% of samples in Maharashtra. But whether this new variant is driving India's ongoing surge can be said only after more data is available.
During a meeting with district laboratories in Maharashtra last week, the National Institute of Virology (NIV) shared limited data showing a break-up of 361 genome-sequenced samples collected between January and March this year.
The headline finding from the analysis: the presence of a double mutation was detected in 220 — almost 61 per cent — of the samples. This double variant was last week classified as the “B.1.617” variant.
What is the B.1.617?
The B.1.617 variant of SARS-CoV-2 carries two mutations, E484Q and L452R. Both are separately found in many other coronavirus variants, but they have been reported together for the first time in India.
The two mutations are found in the virus’s spike protein. The spike protein helps the virus to bind itself to the human cell’s receptors and gain entry into a host cell.
The E484Q mutation is similar to E484K, a mutation found in the United Kingdom (lineage B.1.1.7) and South Africa (B.1.351) variants of the coronavirus.
The L452R mutation has been found in fast spreading variants in California (B.1.427 and B.1.429). It can increase the binding power of spike proteins with ACE2 receptors on human cells, making it more transmissible. L452R can also potentially enhance viral replication.
Together, E484Q and L452R are more infectious, and can evade antibodies.
Where has the B.1.617 been found?
There is limited data. It was first reported from Maharashtra. In January, 19 samples from various districts were sequenced, and B.1.617 was found in four. In February, 234 samples were sequenced from 18 districts, and 151 samples — from at least 16 districts — had this variant. And in March, as many as 65 of 94 samples had it.
So far, Amravati, Nagpur, Akola, Wardha, Pune, Thane, Aurangabad, and Chandrapur districts have presented strong evidence of the presence of B.1.617. Fewer samples were sequenced in other districts, and the variant was found in some. Sequencing is pending for more samples.
Is this variant more virulent?
There is no evidence so far. Most patients can do with home isolation, although clinical experience needs to be combined with genome sequencing data to generate scientific evidence. Clinical anecdotes from doctors suggests the variant spreads faster, is more infectious, can infect entire families, but is less virulent and doesn’t cause dramatically more hospitalisations.
“Most patients are asymptomatic and that is a good indication. But in absolute numbers so many cases have put a burden on health infrastructure,” said Dr Shashank Joshi, an expert on the Maharashtra Covid Task Force.
How much has it spread?
Dr Sujeet Singh, director of the National Centre for Disease Control (NCDC) has pointed out that very few samples from Maharashtra have been sequenced so far, and it is too early to draw definitive conclusions on how widespread the double mutant is. However, the central government had reported in March that 15-20 per cent samples in Maharashtra had this variant; on the basis of the latest sequencing data we know that this number is now over 60 per cent.
Clinicians and district administrators in Maharashtra are reporting that unlike in the first wave, entire families are getting infected in the second wave. This could indicate either that physical distancing and isolation measures are inadequate in the household, or that the virus has become more transmissible.
Could B.1.617 be driving the ongoing surge in Covid-19 cases?
Dr Gangandeep Kang, professor of microbiology at Christian Medical College, Vellore, said 60.9 per cent samples carrying this variant “most likely” showed a link between the mutation and the surge — however, for an accurate answer at least 1 per cent of Covid-19 samples must be sequenced every week. With India at present testing over 1 lakh cases daily, and this would translate to roughly 1,000 genome sequences every day.
“We also need to look at how many people a person is able to infect, and the RT-PCR cycle threshold. We need to do live tracking. Data from January holds little value in April,” Dr Kang said.
Dr Gautam Menon, professor at Ashoka University, Sonepat, and at the Institute of Mathematical Sciences, Chennai, said: “What we have is suggestive but we need more genome sequencing data to understand which variant is driving the number of new infections in different states… To suggest that the rise in cases is due to this double mutant variant, we should have more time points. For instance, if we could say that we detected 30 per cent of this variant in samples on March 30, and then 40 per cent in samples on April 14, that would indicate that the new variant is dominating the spread of the disease.”
Dr Menon too, underlined the need for greater data transparency. “It is possible, although increasingly unlikely, that the cases could also be connected to the previous strain,” he said. “Unless we know to what extent the increase can be attributed to the new variant, we will not be able to determine conclusively whether relaxations in Covid-appropriate behaviour with the older strain drove the increases or whether the increased infectivity of the new variant is responsible.”
Prof Vinod Scaria, principal scientist, CSIR-IGIB, agreed that “we cannot conclusively say that these variants are driving the surge in the second wave”. However, evidence suggests that at least in some states, the B.1.1617 lineage is predominant, and could be contributing to the rise in cases, he said. “This lineage is defined by 15 genetic variants including six spike protein variants. Two of these (E484Q and L452R) are involved in immune escape as well as increased infectivity,” Prof Scaria said.
Can the variant evade vaccines?
Again, the data are limited. Some people have indeed been infected after the first dose, but there is no data on whether their samples were sent for genome sequencing.
“We know that the South African variant is more capable of escaping immune response. We know that UK variant is the most transmissible. But we know nothing about B.1.617 so far, because we are not putting together data to draw conclusions,” Dr Kang said.
Dr Menon underlined that while vaccines are not expected to prevent infection, they certainly prevent severe disease and death. “We expect that this will remain true even with the new variant. The only medium- to long-term solution to deal with Covid-19 is for people to get vaccinated.”
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