‘Variant tracking an essential part of long-term strategy’: Satyajit Rath

Interview with Satyajit Rath, immunologist and visiting faculty, Indian Institute of Science Education and Research, Pune.

Satyajit Rath was trained as a physician and a pathologist and has worked on mechanisms involved in the development and functioning of the immune system, in India and overseas, and later as a faculty member at the National Institute of Immunology in New Delhi. Since his retirement, he has worked in honorary capacities at the Indian Institute of Science Education and Research (IISER) in Pune. He works with the government on issues of science and society-related policy, with scientific journals in an editorial capacity, with small companies on drug discovery, and with civil society groups. He spoke to Frontline on the importance of variant tracking and epidemiological data to deal with the virus and its mutations. Excerpts:

What is the importance of genome sequencing for public health/policy interventions, especially in the context of the new virus variants and sub-variants in India?

Variant tracking is an essential component of a long-term strategy to deal with COVID. This is as true in India as anywhere else in the world. This is because of the huge extent of the spread of the virus, which has likely allowed a lot of virus diversity to be created and therefore to be available for selection, which may well lead to changed virus behaviour, which would need to be monitored and understood in real time in order to enable us to deal with the changes effectively.

There are views that genome sequencing should been done more aggressively and earlier on. The present levels of genome sequencing appear very low.

I could not agree more with both of those statements.

There is a view that sample collection for the sequencing was impeded by the surge. Is that a valid argument?

There may be some bureaucratic element of truth in that. However, sequencing should have begun before it did and on a larger scale than was (or is) done, and both of those are pre-surge issues.

What are we facing at the moment? Is it just a surge due to COVID-inappropriate behaviour as the government would have us believe or is it qualitatively different from the first wave in the sense that there are new mutations and a heightened virulence observed?

Let’s think about it this way; today India’s caseload is (apparently) 280 cases per million people. Brazil’s is 290, the Netherlands’ 410, Sweden’s 480. Yet, which is the country in the greatest COVID distress today? So clearly, it is not that India’s caseload is impossibly high, it is that India has failed to manage to provide medical support for a more-or-less-as-usual caseload.

That makes this a cluster of outbreaks (there is no such thing as a ‘surge’, which implies a relatively orderly and uniform event) more or less like what has been seen at various places in the world at various times over the past year. Has complacency (driven by the government’s messaging) leading to loss of care in physical distancing likely to have contributed? Yes. Is the presence of more easily transmissible virus variants likely to have contributed? Yes. How much, exactly, is the contribution of each? We will never know because we have neither epidemiological data on distancing behaviour over time, nor do we have virus variant data at the necessary scale even in the present outbreak situation, leave alone over time.

VACCINES AND EFFICACY

Is there a need to be sceptical about vaccines, especially since there have been cases of people, including doctors, contracting the infection after two jabs.

No. Instead, it is necessary to stop pretending that vaccines are magic bullets that make each individual impervious to the disease. Very few successful vaccines in use do that. And we already know, even from the preliminary evidence from the efficacy trials, that all these vaccines are reasonably efficacious, but not ‘perfectly’ so.

There is also the theory that there are antibodies that are specific to the receptor binding domain which help counter the entry of the virus and afford greater protection. How does one get to know about what antibodies are effective and what are not? What kind of studies need to be done and are they being done?

That is a theory with a lot of supporting evidence. In fact, that is what scholars think about these ‘neutralising’ antibodies in many, if not most, viral infections. There is quite good evidence for SARS-CoV-2 virus that such ‘neutralising’ antibodies do protect better than non-neutralising ones.

The kind of studies that are not being done as fast as they could be are the ones using natural animal models, especially hamsters, and carefully studying how the various viral targets from different virus strains and/or vaccines, and the various kinds of immune responses to them, work in providing how much protection in the animals.

As for research done on neutralising antibodies, this falls into two categories. One is the desperate high-tech search for monoclonal antibodies that neutralise SARS-CoV-2, so that they can be used for commercial purposes (Regeneron, for example apropos of the Trump medication, and more universities in the global North than one can list). The limitation of this approach is that antiviral agents (monoclonal antibodies, Remdesivir, et cetera) seem to show most effect in COVID-19 when given to patients who are mild-to-moderately ill; but admitting patients in this category to hospital to give them large doses of expensive intravenous medication is not particularly practical so far, at least for India. The second category of research on neutralising antibodies is focussed on working out the structural basis of how such antibodies block the virus from attaching to cells, but I suspect that this will be dismissed as ‘of merely academic interest’.

There is also a view about the comparative efficacy of natural antibodies being better than induced antibodies (vaccine, for instance).

No, there is no evidence that I have seen that supports such a claim that antibodies generated by natural infection are consistently better or worse than antibodies generated by vaccination. They both provide quite reasonable protection by and large.

And while vaccination is a very good way to take, the reasons for that are not related to any such ‘comparative efficacy’.

GENOME SEQUENCING

Is it really a challenge to correlate in a timely manner genome sequencing with epidemiological and clinical data?

Well, it is a challenge in the sense that it takes coordinating between a very large number of experts in different domains on a very large scale, which is never an easy task. However, it is not at all impossible.

Is genome sequencing and its correlation with clinical data just a matter of academic interest? The government seems to think that whatever be the nature of the mutation or the variant, the response in terms of dealing with it would be the same.

No, it is not simply of ‘academic’ interest. But the even more practical reality is that what you describe is a rapid way of keeping an eye on whether there are any virus variants emerging that behave differently and cause a different kind of disease or a more, or less, severe disease, for example. And if such is found, I cannot imagine how the response in terms of dealing with it would be more or less the same.

There has been a shortage of oxygen and some of the drugs recommended in the Indian Council of Medical Research’s (ICMR) protocol. The percentage of people vaccinated is also minuscule. Has India’s public health response been adequate, and should the market be allowed to dictate vaccine policy?

Those are easy answers to very depressing questions; no, and no. Further, sadly, there are still drugs in the ICMR protocol that have not been shown to provide any real clinical benefit (despite trials).

Should we assume that the virus will continue to mutate as part of its evolutionary process and that as long as there are enough ‘hosts’ to infect, it will always be around?

Yes, that is how biology works! It is quite possible that it will settle down as yet another flu-like disease that we deal with, in part by learning how to treat those with severe COVID-19 illness even better, and in part by making new vaccines every few years.

‘THE INDIAN VARIANT’

The government took offence to one of the variants being described as an “Indian” variant by sections of the media.

As for the Indian government saying that there is no Indian variant, there is no question that the government of India is quite correct; geographical nomenclature of this sort is wrong, and as the Indian government noted, the WHO has not referred to it as the ‘Indian variant’ but as the B.1.617 variant. That said, ‘I am shocked, shocked, I tell you’, when I see the Press Information Bureau of the Government of India using these very geographical nomenclatures it objects so strongly to for SARS-CoV-2 virus variants: On January 12, 2021, ‘ Total number of persons found positive with UK variant strain of COVID is 96 ’; and on March 24, 2021, ‘ These include 736 samples positive for viruses of the UK (B.1.1.7) lineage. 34 samples were found positive for viruses of the South African (B.1.351) lineage. 1 sample was found positive for viruses of the Brazilian (P.1) lineage ’, to quote a couple of examples. So only the ‘Indian variant’ is wrong usage, is it? This simply reinforces the interpretation that the government of India is more interested in managing publicity narratives than in anything substantive.

Could you explain the importance of public funding of research in genetics, genome sequencing and so on, and of the epidemiological lessons from the two waves we have had so far?

There has not, in fact, been any multilevel epidemiological investigation, including at the community level, at the clinical level, at the immunological level and at the virological levels (including sequencing) of the epidemic done to the scale and rigour needed in India either last year or this year. So, there is little by way of learnt lessons to narrate. The limitation has not been simply in public funding, though that is quite plausibly the major block. It is also to do with a lack of trust and enthusiasm amongst Indian ‘experts’ from very different domains in order to work efficiently and productively in well-formed collaborations on large scale.

What would you say about the state of India’s public health system given the huge dependence on the private health sector?

I should point out that the ‘public health system’ is a delivery vehicle for health care in all its perspectives. It is not a research activity, although any research done well in the field will need to work with the public health system. And the woeful state of India’s public health system is far too well known to need any more commentary from me.