‘Nothing Very Unusual About SARS-CoV-2 In India That Makes It More Or Less Virulent’

New Delhi: As COVID-19 has ravaged through the world infecting nearly 4 million people and killing more than 274,000 in just five months, there is still no vaccine or drug for the disease. Scientists all over the world, and in India, are rushing to develop these and also to develop technologies for ventilators, protective gear and other medical devices.

India’s premier scientific institute, the Council of Scientific and Industrial Research (CSIR), has tasked its many institutes to focus on five main areas: surveillance, diagnostics, drugs, hospital assistive devices and the supply chain. There are 39 labs under CSIR and one of these is the Centre for Cellular and Molecular Biology (CCMB).

IndiaSpend spoke with Rakesh K Mishra, the centre’s director, about his institute’s work on COVID-19. CCMB has been designated as a validating lab for companies to get their RT-PCR or antibody tests validated and sold in India.

In the interview, Mishra spoke about CCMB’s work on next-generation sequencing, pool testing, antibody testing, the need for private companies to come pick up the research being done by CCMB and whether there is anything starkly different about the SARS-CoV-2 strain in India.

Edited excerpts from the interview:

Could you explain what all kinds of research information CCMB is willing to share with private companies now on SARS-CoV-2?

For example, we grow the virus in the labs in large quantities--we are offering it to several companies to make vaccines or do serological testing. Similarly for the proteins we have in our labs. Companies can come forward and take it up. We can license it at really negligible fees. As a government lab, we are not supposed to make money out of this but whatever technologies can go to the public, we are happy for that.

We are happy to share information on the virus and proteins but the genetic information we are gathering, we are not making public yet. This is not specific to our labs in India but is an established system everywhere. We will deposit the sequence in the public domain when enough sequences have been done, and everyone can use that information. This is a very good and open way of working. There are now more than 12,000 sequences in the public domain already.

On the virus and proteins, we are already in negotiations and have finalised agreements with several companies who can take it forward for making vaccines and drugs. Not all this will bear fruit, but at CCMB alone, we are interacting with some 675 companies at the moment.

There is enthusiasm from companies for a few reasons. Firstly, this is a challenge for anyone who wants to have a long-term standing on the health system. Second, it is a lockdown, so if you are working on COVID-19, at least you are allowed to work and run your lab. Third, COVID-19 is going to be a long-term issue we have to deal with, so it is good for people to start getting involved.

Is CCMB also working on creating diagnostics for COVID-19?

We are interacting with Biocon and Syngene to develop something really dramatic called ‘Next Generation Sequencing’. With this project, we will be able to test 10,000 or 20,000 samples in one go. That technology basically involves collecting samples from many places and doing them in a specialised bar-coded fashion, pooling them and bringing them to one place--like CCMB or wherever there are adequate facilities--and then doing the sequencing for diagnosis. To clarify, this is not going to be genome sequencing, it will be sequencing for diagnosis.

This technology has some demands though, on logistics. Governments have to accept and agree to use this because it operates all the way from sample collection point, not just at the testing point in labs. A large number of cases need to be tested. So when a number of people are concerned, India is at both an advantage and disadvantage for this.

The idea for this came from work at the Broad Institute in the US, a top genomics institute. We began working on this, discussing, refining and moderating the idea in a way that becomes economically viable. We are working on a system that will make things cheaper and faster. We are excited about this.

Although we are still developing this technology, we do hope it will be useful for diseases like COVID-19 or other things, now or in the future. There’s nothing special about COVID-19 in the sense, the type of testing one has to do is the same as for many other diseases. But the difference here is we need to test such large numbers and very fast. So if we succeed, this technology can solve this problem for future pandemics.

One question has been coming up often in government press conferences and has been a matter of speculation: Are Indian scientists seeing anything special in the mutations of the SARS-CoV-2 virus? Anything stark in the strains that you are studying? Anything different in terms of its virulence?

A very basic feature of the ‘corona’ family of viruses is they mutate very fast. It is normal, to be expected. The SARS-CoV-2 virus is mutating. That is precisely the reason the whole world is sequencing it. Otherwise why should you sequence the same virus 12,000 times? Variations are very useful so we can track the virus. It is like lots of dots, connected by arrows. The direction of the arrows shows how the dots are related to each other. This is why we are also keen on sequencing very large numbers.

On the Indian strain and isolates, we have analysed them. To answer your question in a very straight way, so far there is nothing very unusual about the Indian isolates to suggest that they are more or less virulent. There is nothing to be worried or happy about. It is really like other strains. It has its own signature that helps us track the spread of the virus. But regarding whether [there is] anything very different about the Indian strain, we will be able to make a very firm statement on this once we have, let us say, 500 or 1,000 genome sequences done, which will probably happen in May.

One more thing we are working on is whether there’s a genetic difference among Indians that is determining how we handle the virus. So we are taking samples of patients with severe or mild symptoms, or asymptomatic cases and looking at their genomes. For example, in mild cases, what could be the reason that these people only experienced mild symptoms? We will know this in a few months. It is a long-term research. A few months is not a long time, but of course in a desperate time like COVID-19, it is a long time.

What are some other areas of work around COVID-19 which your institute is involved in?

We are one of the few centres in India that is doing pooled testing of samples. We are doing this in the state of Telangana. Given that there is a shortage of testing kits, pooled testing saves on the reagents used. It also saves time and allows us to test a larger number of people.

Pooled testing works by doing a small number of tests, among pools of people, which gives the results for a larger number of people. So for example, by doing 100 tests, we can get the results for 500 people. If positive cases turn up in some of those pools, then we can go back and re-test within those areas. We have made a protocol on how to do this and shared it with other testing labs.

This should only be done with RT-PCR tests though, not antibody tests. Telangana has not allowed any antibody testing, even before the recent issue around faulty antibody test kits.

On the issue of antibody kits, there has been a lot of controversy around its pricing but also on its quality. The government has now blacklisted two Chinese companies. What are some issues around using antibody testing that we need to be careful about?

With antibody testing, you will not be able to detect the antibodies in the first 8-10 days of infection. But this is also the time when the infection is spreading. So if a person is tested for antibodies in the first week or 10 days of infection, their results will come negative. They will have a false impression that they do not have infection. So antibody testing does not help to check the spread of the infection. It only helps to sense where all the spread has been and whether one had exposure to the virus. It helps to decide overall management of the pandemic, who has the antibodies, who does not have the virus, who can be deployed in some areas and who can go back to work.

[Editor’s note: The WHO has warned that there is no conclusive evidence that antibody tests prove that an individual is immune or is protected from reinfection, and warned against depending on “immunity certificates” to allow individuals to get back to work.]

What issues will we face as a country because of not having enough antibody kits?

Antibody testing has a lot of uses also. ICMR [Indian Council of Medical Research] has banned some kits from China but there are South Korean kits [too].

This time also gives scope and space for indigenous kits to come. We at CCMB are growing the virus, we can make the kits with the help of some companies. We are now able to express almost all the proteins of this virus, they are also potential material for making such serological or antibody-based kits.

At CCMB, we cannot do business, we cannot do mass-scale production. But we do the initial risky work of exploration. Once things stabilise, private companies can come forward. They should see scope for business. Now because of this crisis, scope has increased. We might have indigenous kits soon.

(Bhuyan is a special correspondent at IndiaSpend.)

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