Dr Priya Abraham was barely two months into her job as the director of the National Institute of Virology, Pune, when her lab stumbled upon a specimen that would later be confirmed as the first Covid positive case in India. Among the Indian Council of Medical Research’s 27 institutes, the NIV’s mandate is to be a watchdog against viral infections. Its microbial containment facility in Pune has been working with the actual living virus of the SARS-CoV-2 delta variant. In an exclusive interview, Abraham tells about the “trial by fire” at the NIV, the current “relatively quieter” period, the changing behaviour of the virus and why it is too early to bring down one's guard. Excerpts:
What is your current assessment of the Covid-19 situation?
The virus has not gone away. It is very much in our midst and it is equally highly infectious and transmissible even now. But we need to prevent its fast spread because the quick transmission will encourage the creation of mutations. We are slowly upping the percentage of people who are completely vaccinated. A good number of people are adhering to the social measures required to curtail the spread. So we are actually seeing a lower number of cases across the country, except in some states where it is still very high. Vaccines are extremely effective in preventing serious disease and deaths due to the virus, including the delta variant, but it is a fact that they are not able to give more than 90 per cent protection against picking up the infection. Hence, following Covid appropriate behaviour is still recommended.
How long can the vaccines protect us?
At least for six months. The big manufacturers are actually looking at studies to see when we can give boosters. In high-income countries, the delivery of boosters is happening because of the wide availability of vaccines and shots. So the m-RNA vaccine manufacturers have begun to recommend boosters for individuals who are immunosuppressed, more vulnerable to developing serious forms of disease and whose immunity is sub-optimal. As of now, we know that a very small proportion of the world has actually got vaccinated. So the data is still evolving for us to know exactly how long a vaccine can protect us. More real-world data is awaited, but we know approximate six-month protection is definitely there.
Are the recommendations for booster shots propaganda by vaccine companies?
It may be. I know of those who have taken the fourth dose against Covid-19 in a rich country within this year. Isn't that insane? There is no formal recommendation in this regard yet. Also, I believe we must speak up against vaccine inequity in the world with some nations vaccinating almost their entire populations while others barely manage to have 5 per cent vaccinated. We have vaccinated only a little over 25 per cent of our population till now.
There have been reports that a fourth wave is hitting the US. Should we worry about a fourth wave, too?
To me, a wave is a significant surge in cases—a peak that comes in a particular geographic region. We have clearly experienced two waves that were fairly significant across the country. But, as a nation, we haven't gotten our third wave yet because we haven't seen that kind of unprecedented or notable surge in cases after the peak of the second wave. We might invite it because of our lackadaisical behaviour during the approaching festive months and elections in some states, and also because of our inability to penetrate pockets with sufficient vaccination. There is Diwali, Dussehra, Christmas, New Year and then the elections early next year. If we all adhere to public health and social measures, then any wave will not be significant. But if not, then it will be upon us sooner than we think. In some parts of the US, there has been vaccine hesitancy and scant regard for masking. So, yes, a fourth wave is not completely impossible in such situations and smaller waves thereafter, too.
Are there new variants lurking among us?
The delta variant and its sub-lineages, close to 35 of them, are very much among us. It is just that natural immunity has increased—some were exposed, some were vaccinated, some have been careful and states have not completely opened up. No new variants have been found yet, but there is every possibility of dangerous variants showing up in time to come because RnA viruses are known to undergo mutations. What encourages new mutants to form is the spread from individual to individual.
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What is the latest new knowledge you have come about which can tell us more about the virus?
That over 85 per cent of all breakthrough infections we have seen even after full vaccination have been due to the delta variant. That is the latest and most troublesome piece of information. A study was done across 17 states and union territories from March to June by ICMR along with some of the Virus Reference Diagnostic Laboratories of the Department of Health Research. We found that of all breakthrough infections, over 86 per cent, were due to delta.
What is the next expected form the virus will take and how would it behave after 24 months of creating havoc?
I would imagine that as more and more people get vaccinated, many have already experienced infection and transmission comes down a little, this might go into an endemic form. Like what happened with the H1N1 pandemic. There will not be any more ferocity of spread as we saw at the peak of the second wave. Perhaps in the next four to five months, the infection will become endemic. But that is only if we don't become lax. Especially as the virus continues to be highly transmissible with an R-naught average (a figure expressing the average number of cases of an infectious disease arising by transmission from a single infected individual) around 6.5 to 7, which is much higher than many other viruses. This means you can pick up infection even if you are vaccinated, transmission can also happen but you are unlikely to have serious forms of the disease. Endemicity comes as more and more people get exposed to the virus or vaccine and then the pace of spread slows down.
Should children be vaccinated?
Children, when exposed, do get infected and they can transmit the virus. However, most children mount such a good response that they actually do not even have a detectable virus because their immune response is able to neutralise the virus effectively. It is a broad-based and vigorous immune response which releases certain cytokines that also prevent immune-related damage of the lungs, which was commonly observed in adults. So, even if unvaccinated, most children will not develop complications resulting from Covid-19 infections. Children, too, eventually get the vaccine.
Which vaccine technology—DNA, mRNA, recombinant—works best against Covid-19?
There are 17-odd vaccines world over and all are efficacious in preventing serious forms of disease, hospitalisation and death. All are at different levels, where the efficacy varies from 70 to 90 percent. They all target primarily to deliver the spike protein in different ways to the body so that the immune system will see it and produce an immune response. Now they're beginning to use a live attenuated virus which is the weakening of the virus by taking off its virulence so that its ability to cause serious disease is curtailed. Novovax, which is a protein-based vaccine, is also there and so is the latest by Zydus Cadila, the ZyCoV-D. So, we need more data to really know which ones are doing exceedingly well. As of now we only have to wait as the data is so limited.
What is your take on the debate on heterologous vaccination, that is administering of a mix of vaccines?
Our research on this subject at present is still in the publication stage. We looked at the immune response in the case of heterologous administering of vaccines but we cannot tell the findings until it gets published. But it was very good. Even WHO is not ready to give the guidance now.
Tell us about the latest breakthrough research at NIV that can also be applied to Covid-19.
In that which can be applied to Covid-19, the latest is our work in the area of monoclonal antibodies against Covid-19 with a pharma company, which is yet to be published. Zydus Cadila and Roche have come out with monoclonal antibodies that are readymade and are targeted antibodies that are directed against the specific regions of the spike protein of the virus. These antibodies can be potentially used as therapy in early cases that have not progressed to severe disease. This is part of a collaboration with the industry. We have done experiments on animal models like hamsters. We can infect hamsters with the virus and then give them the monoclonal antibodies and see whether replication, spread and damage to tissues can be arrested because the monoclonal is a highly targeted antibody against a specific region of the spike protein.
In a way, the pandemic has been a great eye-opener as it has taught us the importance of scientific collaborations and how they should ideally work. Most of the time, there is a lack of clear communication channels and labs don't know what their contemporaries are doing.
When the world has been brought to its knees, it is the time to have transparent collaboration across the world. It's not right to have a finding of a novel virus and keep it to oneself. Where did the delta variant emerge from? Today that is the number one variant across the whole world. So now we are slowly learning to collaborate well now. Initially everybody was doing their own thing.
Your lab grows and propagates live viruses. Other labs deal with pseudovirions. You also capture bats and contain them for research. This is all very similar to what the Wuhan lab was doing. Is there a chance for a lab leak?
We are the fifth country in the world to establish isolation of the virus—you know the virus was isolated in cell lines and we were able to propagate it. We achieved it in March last year. This really helped with the vaccine because we were able to do pre-clinical trials—we vaccinated hamsters with the candidate vaccine's three-dose regimen and gave a gap and then challenged them with a live virus. This is the ‘acid test’ for the effectiveness of the vaccine. So, before the vaccine actually came to human clinical trials, we did these preclinical studies in hamsters and in non-human primates (monkeys). It is done in our highest containment facility that is a biosafety level 4 lab. This highest containment laboratory has protective measures needed to protect workers, the environment, and the public. We have studied the fresh tissues of the bats to understand whether bats are reservoirs of other viruses such as the Nipah virus as well as coronaviruses.
We found coronaviruses in our bats but not the RaTG 13, which comes to be the closest ‘cousin’ to SARS-CoV-2. The BSL-4 laboratory has its own dedicated air supply along with vacuum lines and decontamination procedures such that nothing infectious from inside the lab goes out, following the strictest laboratory norms. We have bat specimens in our lab even as we speak. Yes, we capture them for identifying the source of certain zoonotic infections and this is why we use fresh frozen tissues for such studies. We have caught bats recently to look for Nipah virus infection following the recent case but none that we captured had evidence of current infection, though there was suggestion that they harboured infection previously.
Is there a possibility that India would become a hotbed of zoonotic diseases?
Yes. Zoonotic infections, which are infections coming from animals to humans, will be a big concern for humans today. In India, Kyasanur forest disease is a case in point. This is monkey fever which is now seen in Karnataka, Maharashtra, Goa, Kerala and Tamil Nadu. The virus infects humans when they go foraging inside forests. Ticks from monkeys and forest rodents bite humans. Bats also are a reservoir of a number of viruses. Rabies is another zoonotic disease caused by exposure to rabid dogs, cats, cattle, foxes and even bat saliva.
Virologists have achieved so much. Why are we still not able to get a hold on the influenza and common cold?
Because the makeup of the influenza virus is constantly undergoing antigenic shifts and antigenic drifts. In fact, the rate of mutation of the Covid-19 is also not as high as that of the influenza virus which keeps changing from time to time and hence, its various strains are constantly monitored the world over. The common cold virus is caused by so many different viruses that it is very hard to pin it down to a genome. It has segmented genomes as against the SARS-CoV-2 which has a continuous genome. Also, it is not life threatening, hence it isn't a priority. Last year we had very little influenza cases because people were indoors. This year it has jumped up because of the opening up of businesses. The mask can prevent the transmission of the influenza virus.
But until when can we keep wearing masks?
Until the immunity in the population comes to such a level that it becomes endemic.
Everyone says that presence of antibodies means you are protected against the virus. But there is no data on how much protection is offered by antibodies. It seems to be a statement with no basis in numbers.
Yes. It is yet to be known to the entire world. All the premier research organisations including the WHO are still trying to find that critical antibody level which is truly protective. But the thing is that along with the production of antibodies what is also needed is cell mediated immunity which comes from a group of cells called b and t lymphocytes and make memory cells which are stashed away in the lymph nodes for memory in the future. So, if you encounter the virus again, they will come out and fight. So now the absolute values of both, cell mediated immunity and antibodies, is not known yet. But science says that these are positive indicators.
Tell us about the safety of labs in handling SARS-CoV-2.
A clinical specimen of a patient who is suspected to have Covid-19 infection can be handled in Biosafety lab level 2 because then one is not working with the live virus. One is simply artificially amplifying the virus in RT-PCR so the risk is less than when one grows the actual virus and makes it replicate. The WHO recommends Biosafety lab 3 for growing the virus and propagating it.
But we have taken the utmost precaution and handle the live virus in Safety level 4 which is the maximum containment. Any air that is ducted out of the closed cabinet is not released out from the back of the building but is actually filtered and decontaminated until it is rendered safe. The workers in positive pressure suits and double gloves are exclusively trained to handle this virus so that there is no laboratory accident.
What has been the toughest and most challenging aspect about being a virologist during the Covid-19 pandemic?
Looking back, it was possibly trying to finish those pre-clinical trials, particularly the non-human primate studies (monkeys). The work was on a very tight timeline, around 70 days. The pressure to delivery was very challenging. Even to procure the non-human primates was very difficult, because usually we capture them in frequent human dwellings but during the lockdown they went back into the jungle.
So, we had to go chasing them in the jungles and last year this time one of our scientists went to the forest on Vijayadashami. Once we had done the experiments, we had a lot of animal activists after us questioning why we captured the primates for experiments and could've done it on humans. But we can't. There is a certain protocol and method of following it - start in vitro, then go in vivo small animals, large animals then human clinical phase 1, phase 2, phase 3. It was crazy to be answerable to everyone.
Which is the emerging public health problem in India?
Dengue and chikungunya will continue to be our problem areas. We went on a hunt for dengue and chikangunya and found a Zika in Balsar in an older lady, who became the first Zika case in Maharashtra. Then we started screening pregnant women.
Chikungunya and dengue do not have specific antivirals, nor do we have a vaccine yet. KFD and CCHF—the Crimean Congo haemorrhagic fever (CCHF), an acute, highly-contagious and life-threatening disease, found in Gujarat and Rajasthan in 2017—is also on our radar. We found it in north Maharashtra sometime back.