December 7, 2023

Key virus strain found in October but its gene study stalled; a new variety appears

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Now, a third mutation in the B.1.167 has been identified and experts are hoping that this time, given the alarm bells ringing all around, the pace of intervention and follow-up picks up.

The Indian-origin double mutant strain of the coronavirus, B.1.167, that many experts say could be behind the rapid climb of the second Covid wave, was first detected way back in October 5 last year through genome sequencing of a virus sample.

Because both the mutations, E484Q and L425R, were located in the virus’s critical spike protein — that binds it to the receptor cells in the body. Its destructive potential should have raised immediate red flags and led to widespread gene surveillance to look for its prevalence and spread.

Instead, the genome sequencing exercise, already running at a snail’s pace, slowed down further between November and January due to lack of funds, absence of clear directives, and, possibly, also disinterest because of the steadily falling Covid curve.

Now, a third mutation in the B.1.167 has been identified and experts are hoping that this time, given the alarm bells ringing all around, the pace of intervention and follow-up picks up.

Genome sequencing, the study of genetic structures of an organism and the changes happening therein, produces a wealth of information that can throw light on the origins of the virus, the routes it has taken to reach a particular geography and the changes, or mutations, that are making the virus stronger or weaker.

Such information is crucial not just in designing control measures, but also in the development of drugs and vaccines. In fact, the early availability of gene sequences from China, United States and some other countries is one key reason why a vaccine could be developed in such a record time.

In India, however, genome sequencing crawled – in the first six months, India had barely done a few hundred sequences, when countries like China, the UK and US, had done several thousand and submitted these in public global depositories for scientists across the world to study.

It was only in January this year that the government set up the Indian SARS-CoV2 Genomics Consortium (INSACOG) to expedite the gene sequencing effort from India through a network of 10 laboratories.

“The whole point of gene sequencing is to remain ahead of the curve, anticipate what new variants of the virus are likely to emerge, how they are likely to behave, and what can be done to contain their spread in the population. More the sequences, greater is our information about them, and more effective our response can be. Unfortunately, India has been well behind the curve on this front. We have been reacting to the developments, instead of anticipating it,” said a scientist associated with the sequencing effort.

Gene sequencing is time-consuming and costly. It can take three to five days to develop one sequence, once the virus sample has been extracted, cultured and sent to the laboratory. Only a few government laboratories have been doing this gene sequencing work, which involves a huge amount of computer processing time. Developing one sequence can cost between Rs 3-5000.

The INSACOG was initially allocated Rs 115 crore for a six-month period. The money was to come from the Central government. However, no additional allocation was made and the Department of Biotechnology was asked to find the money from its own resources. The first tranche of money could be released only on March 31, the last day of the financial year. The allocation itself has been reduced to about Rs 80 – crore because that’s what the DBT could come up with.

In the meanwhile, laboratories like the Centre for Cellular and Molecular Biology in Hyderabad, and the Institute of Genomics and Integrated Biology (IGIB) in Delhi, have been sequencing the genome using their limited funds.

“Labs have very limited resources. To find money to do something extra is a very difficult proposition. Most labs diverted money from other running projects to work on sequencing, in the hope that they would be compensated sometime later. But funds were just one problem. There has also been lack of clear directives and goals,” said another scientist who is also working on sequencing the virus genome.

The case of the double mutant variant is a very good example of how policy stumbled. “It was detected way back. It was found again in November and December. By February, this variant is exploding, almost coinciding with the surge in Maharashtra. The discovery should have been acted upon immediately. But nothing happened. Now we are fire-fighting,” said the scientist quoted earlier.

There has been some improvement. Since INSACOG began work in February, more than 13,000 sequences have been developed from across the country. This is still not adequate.

The stated objective of INSACOG is to facilitate genome sequencing of five per cent of all the emerging new cases. That is an ambitious goal, considering that over 2.5 lakh new cases are being detected every day.

To meet the 5%-goal, more than 12,500 samples would have to be sent for sequencing. In reality, less than 1 per cent samples are currently being sequenced.

But already some information is emerging that can be red-flagged.

Multiple sources have told that the Health Ministry was last week briefed about the possibility of this double mutant variant developing another significant mutation, and becoming a “triple-mutant.” And three different varieties have been detected.

Two of the triple-mutant varieties have the new mutation in the spike protein and have been found in samples collected from Maharashtra, Delhi, West Bengal and Chhattisgarh – all second surge states. A third version of the strain has the mutation outside the spike protein but is still considered significant and has been observed in 17 samples, again from Maharashtra, Delhi and West Bengal.

“As you can notice, West Bengal seems to be becoming the hotspot for such mutations. The new triple mutant could make the virus even more capable of evading human immune response,” said a source. “We need to do a lot more sequencing of a lot many samples.”

Given India’s Covid curve, its rapidly increasing numbers and these new strains, the world is watching. Reports by the US-based Andersen Lab at Scripps Research, San Diego, as of April 18, show that 566 sequences in the B.1.617 lineage have been detected in India since this lineage was identified on October 5; followed by UK (133) and United States (52).

Data also shows that in West Bengal, the B.1.617 strain was found in 133 out of 1373 samples; it was followed by three other surge states Maharashtra (122/1931), Karnataka (20/539), and Gujarat (16/859).

Said Karthik Gangavarapu of Scripps Research and part of the 20-member team studying global genome data: “In India, one thing to keep in mind is that B.1.617, seems to be increasing in prevalence but when you actually look at the number sequenced per day, that number is quite low. For example, in the last 10 days we are seeing under 10 sequences.”

“The question is we don’t know which variant is contributing how much to the second wave,” said Gangavarapu. “We don’t have evidence either way. It could be B.1.617 or the B.1.1.7 (UK variant) or both. That is why genomic surveillance is very important.”

The South African and Brazilian strains have added another dimension to the challenge. On April 16, the Health Ministry said that of the 13,614 samples processed, 1,189 samples tested positive for variants of concern. These include 1109 samples with UK variants; 79 samples with South African variant and one sample with the Brazil variant.

It did not give any figures for the double-mutant saying it was found in several countries and “higher transmissibility of this variant is not established as yet.”

(Tomorrow: Vaccine rollout: the booster dose that went missing)

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