Dr Anurag Agrawal: ‘Global surveillance is important’

Interview with Dr Anurag Agrawal, Director, Institute of Genomic and Integrative Biology.

Dr Anurag Agrawal, Director, Institute of Genomic and Integrative Biology.

THE Institute of Genomic and Integrative Biology (IGIB), under the Council for Scientific and Industrial Research, is an integral part of INSACOG (Indian SARS COV-2 Consortium on Genomics), a consortium of 10 national laboratories. INSACOG was set up in January with government funding from the Department of Biotechnology.

Dr Anurag Agrawal is a pulmonologist and a medical researcher who heads the IGIB. He spoke to Frontline about the various variants of concern (VOC) and said that the variant responsible for the present surge could be the B. 1.617 found in some parts of India. He also said that for efficient discovery of new variants of interest [VOI] and VOC, better integration of clinical, epidemiologic, sequencing, and biological data was needed. Excerpts from the interview.

In terms of genome sequencing, what do we know at present of the SARS-COV-2 variants and mutations that exist in various parts of India today and their correlation with clinical data?

In India, of the six known variants of concern [country first reported]—B.1.1.7 (United Kingdom), B.1.351 (South Africa), P.1 (Brazil), B.1.427 and .429 (United States), B.1.617 (India) — only B.1.1.7 and B.1.617 have shown association with outbreaks. Others are either rarely seen or in decline. However, these situations are dynamic.

There are different variants and different mutations in parts of India. Within one State two different variants are found. Is this normal? Delhi for instance has both the U.K. variant and a double mutant variant. You spoke of sub-variants having an effect on the present surge. Could you please elaborate on this?

It is natural for variants of similar transmissibility to co-exist. When one is much more transmissible, it replaces the other. Such dynamics are being seen that allow us to judge transmissibility. As of now B.1.617.2 looks to be the fastest growing. This may have been a major factor in the surge.

What are the specific conditions that allow for the rapid mutation of a virus? Which are the ones that pose a greater risk?

All viruses mutate. Today in India, the large number of infections is the most permissive factor for the emergence of new mutants. Other factors may be inappropriate use of anti-virals and plasma therapy.

What is the importance of detecting mutations other than scientific purposes? How much more serious is a double or a triple mutant virus? How does such knowledge influence public policy?

Detecting mutations, marking the ones that appear to be concerning, and confirming is part of the transition from new variant to VOI/variant under investigation[VUI], to VOC. Knowing the entry and growth of VOC helps in public health preparedness. Ultimately, all current variants can be controlled through COVID appropriate behaviour and masks (and vaccines).

Genomic surveillance globally is considered to be patchy. There seems to be great inequity in such surveillance. How does that complicate matters as a sufficient degree is required to track mutations and their possible effects?

Future VOCs may emerge anywhere, thus global surveillance is important

Does a sharp surge necessarily impede genomic surveillance? Is it a fact that India’s sample for genomic sequencing is not adequate?

The sampling and sequencing is sufficient to identify VOC spread pattern and inform public health response. For efficient discovery of new VOI and VOC, we need better integration of clinical, epidemiologic, sequencing, and biological data. Increasing sample size is simpler, but not the real answer.

How many samples are required for a proper study? Do we have the manpower, infrastructure for this? If not, should we as a nation be working on it?

There is no standard sample size. It depends on the question. To know a dominant local VOC, we need only a small number of samples per time per region. The current INSACOG strategy based on World Health Organisation recommendations is fine. To discover a new VOC requires different strategies, again not always based on large samples but selective samples such as vaccination breakthroughs or severe cases. We have sufficient infrastructure for selected sequencing, as above. Full integration would require digital health records, national systems and more investment into biological studies.

Why is B.1.617 a variant of concern and interest? What distinctive features does it have as opposed to others? Is it possible that some variants, including B.1.617, can dodge the vaccination shield?

Its main feature seems to be higher transmissibility. The reason seems to be only partly immune escape. Better binding to ACE2 receptor by L452R mutation (the double mutant) and greater syncytium (fusion of infected cells with neighboring cells) formation by P481R mutation seem important. In-vitro neutralisation studies suggest that vaccines will work in preventing severe disease. But yes, it is possible that the vaccination shield can be dodged by variants.