Updated: January 25, 2021 10:12:24 am
Dr Shekhar Mande talks about “guarded optimism” over drop in Covid-19 cases, says effectiveness of vaccines will be monitored for the next two years, and explains hygiene hypothesis and why he believes our immune system can deal with new strains. The session was moderated by Resident Editor (Pune) Amitabh Sinha
DR SHEKHAR MANDE: A global health emergency like Covid-19 was foreseen for the last several years. We did not know in what form it would come, but for 20-25 years it was being predicted that the next pandemic was just around the corner. And, even after this pandemic is over, there is a possibility that another one might still be around the corner. So, we should be prepared for that.
In India, the first Covid-19 case was reported on January 30, last year. We discussed the issue at a meeting of the directors of all the laboratories under Council of Scientific and Industrial Research (CSIR) on February 25-26. The World Health Organisation declared the pandemic on March 11, almost 15 days later. By that time, our strategy was already in place and it was rolled out by mid-March. There were several aspects to the response. The first vertical was surveillance, which we are doing even today. It includes sequencing different viral strains across India, conducting air sampling surveys to know how far the virus travels etc. The second vertical was diagnostics. You would have heard about, for example, the Feluda test kit that has come from the CSIR’s stable… We did dry swabs, which reduces the cost of RT-PCR tests by half. The dry swab method has also been approved by the Indian Council of Medical Research.
The third vertical is interventions, where we are looking at both vaccines as well as drugs. Favipiravir is already being sold in the market by Cipla, the process for which was generated in the CSIR… We have also taken cognizance of traditional knowledge and some trials are going on along with Ayush (Ministry).
The fourth aspect is medical instruments, and there have been several innovations here too, including the BiPAP ‘SwasthVayu’ Ventilator. It’s for people who are not critical but their oxygen level needs to be enhanced. We have already supplied 1,200 such ventilators to the Delhi government. We have launched ‘rapidly deployable hospitals’ which can be set up in remote locations in about five days and six such hospitals are ready in Himachal Pradesh now.
There were two principles that we used while bringing about these innovations. Number one, there has to be industry’s involvement, like Cipla’s in the case of Favipiravir. The second important point that we discussed was that all the components must be made in India, so that we don’t have to depend on imports. So with both these principles, we are now in a position to scale up everything for the benefit of society.
AMITABH SINHA: In your assessment, is the Covid-19 graph in India in an irreversible decline, or is there still a fear of a second wave? Also, can you tell us a little bit about the different Covid-19 strains that have emerged?
Are we over the pandemic in India? There is a very guarded optimism about it. The number of cases is going down. It’s hovering between 16,000-20,000 cases per day in India, compared to about 2,20,000-2,40,000 per day in the US. But we are guarded, because the pandemic isn’t over. If we let our guard down, there is every possibility of a second wave. So, we must be very, very careful when we say that the number of cases have gone down. Compared to other more developed nations, the defining feature in India has been the early lockdown. It gave us the opportunity to tell people about the dangers of the pandemic, and to prepare to handle the pandemic as well. We were able to educate everyone that when you step out of the house, don’t forget your mask, wash your hands, keep distance, and that actually helped. You don’t see this happening even in the most developed countries.
About the strains… Every virus mutates. There is an interplay between the host (the human body) and the pathogen, which is the virus. Now, as the pathogen tries to establish an infection in the host, the latter tries to get rid of the pathogen. (As the virus mutates) our immune system tries to get rid of it (the mutations), unless a very large number accumulates simultaneously. The UK strain can accumulate 17 mutations in its spike protein. A virus has millions of atoms coated around a sphere, and we actually see only 17 mutations… Therefore, it is believed that the human immune system is sufficiently capable of getting rid of even the new strain.
ESHA ROY: Whether it’s the UK variant or the South African variant, what is the Indian government doing to identify and stop the spread in the country? Also, what have been the takeaways from genome sequencing done so far? For instance, are some strains more virulent than the others?
The standard strategy that all governments around the world have adopted is testing, tracking, tracing… We sequence strains from those people who have a history of travel to the UK etc. Once we know that the person is UK-positive, we isolate the person so that the virus doesn’t spread to others. That’s the government’s strategy. Also, you know about SpiceHealth. We are trying to actually collect samples at airports and then reduce the number of days required for sequencing. That’s precisely what SpiceHealth will be doing at different airports in the country.
Now, are any of the new variants more virulent? It’s not proven yet. What is proven is how transmissible they are. What is the probability of one person to transmit a variant to another person, which is typically defined by the R-number. And these variants (UK, South Africa) are actually known to be more transmissible, about 60 to 70% more… However, it is not known whether they are more lethal or not.
ANURADHA MASCARENHAS: Why don’t we have a single drug that is fully effective against Covid-19 so far?
Development of any drug typically takes 10-12 years. So, when Covid-19 came up, the easiest strategy was to go for ‘repurposing’. As part of the strategy, drugs which are already in the market and are ‘generally regarded as safe (GRAS)’… we can find a different use for that particular drug. There are roughly about 3,000 drugs which are in the market for human consumption, and must be tested for Covid-19… That is how Favipiravir and the others came up… As for new drugs, they will take another four-five years to come out.
ANURADHA MASCARENHAS: Professor Rohini Godbole from the Centre for High Energy Physics at IISc, was awarded the Ordre National Du Merite, among the highest distinctions bestowed by France. How can we encourage more women to join STEM sectors?
There is a leaky pipeline somewhere. Let us accept that fact. At the school level, there is equal opportunity for everyone. As we start climbing up, unfortunately, the number (of women) drops dramatically. And, by the time you come to the job market, the numbers are even lower, and at the senior leadership level, the numbers are pathetic. So how do you encourage (women to join STEM sectors)? First, let us accept that we have not done well on these numbers. Then, one has to continuously and proactively keep talking about these issues in the public space, even if the truth is inconvenient. Secondly, people like me, who have the advantage of being in an administrative position, must try to correct things… At the CSIR we have ensured that all advisory bodies, committees, have a gender balance. We have tried to do the same in senior leadership positions too. It’s a huge challenge. When I joined the CSIR two years ago, neither of our 37 laboratories had a woman director. Today, four of our laboratories are headed by female directors. It is still a pathetic number, and we are working towards taking it to 17-18…
KAUNAIN SHERIFF M: About 55 lakh doses of the Covid-19 vaccine will be administered purely based on safety data of the Phase 1 and 2 trials. We don’t have efficacy data for the Bharat Biotech vaccine. Do you think the scientific principle that is being applied now is sustainable?
… We are losing hundreds of people every day, right? In the next three-four months, let us assume you lose about a 100 people a day. That means about 3,000 people a month, and about 10,000 deaths in the next three-four months. That’s a low estimate. The higher estimate could be 50,000 people. Now, a vaccine candidate has been proven to be safe, there has been no adverse impact in Phase 1 clinical trials as well as in the pre-clinical trials in animals. In Phase2 clinical trials, you show that (the vaccine) is immunogenic, that it is eliciting sufficient immune response in a human being. So, the hope is that since it is generating an immune response, the human immunity can likely take care of the virus. The criticism has been that we could have waited for another four months for Phase 3 clinical trials to get over… (But) you are going to risk the lives of 10,000-50,000 people. That’s the first risk. The second risk is that mutants are very rapidly emerging around the world. If you are a regulator, what would you do? Would you save 50,000 lives? Would you allow mutants to arise or would you go for a vaccine which is known to be safe and elicits a response, although its efficacy is not well known?
See, there has been no adverse impact of taking the vaccine. You are not being subjected to any kind of risk, you are not going to develop any adverse reaction, there is no serious illness that you are going to develop… Essentially, if the vaccine generates an immune response against this particular virus, that’s good. But even if it does not elicit a response, you have not lost anything per se. There is nothing adverse that you have done to yourself.
KAUNAIN SHERIFF M: In one of your earlier interviews, you said there is a difference between efficacy and effectiveness of the vaccine. Can you elaborate?
Efficacy is calculated in clinical trials on subjects that have received either the vaccine dose or the placebo. Neither the person who is administering the vaccine nor the person who is receiving it knows whether it is the actual vaccine or a placebo. At the end of the study, which takes a few months, you find out who got what. For example, in the Moderna trials, about 30,000 people were given a dose of either the placebo or the vaccine, and 196 developed Covid-19 after a few months. Of these, 185 had received the placebo and 11 had received the Moderna vaccine. So the efficacy was 95%.
Based on efficacy, the regulator decides to give approval for the vaccine to be administered to the general population. Now, in the general population there are people who were excluded from clinical trials. People with comorbidities, people who are above the age of 70… So now you will measure things in the entire population. In the real world scenario, the numbers will change from 95%… That is effectiveness. There is a subtle difference and it is being monitored post vaccination. There is going to be very close monitoring for two years as part of the pharmacovigilance process.
HARISH DAMODARAN: What is the total budget of the CSIR and how much of that is spent on sponsored or demand-driven research?
Till about 10 years ago, there used to be enormous delays in flights in Delhi due to fog. All those delays have reduced significantly. A transmissometer (for the determination of visual range) has been installed across 100 airports in the country. It is called Drishti and was developed by NAL (National Aerospace Laboratory, a constituent of the CSIR). Today, Delhi has three-five installations of Drishti.
We heard the news of the government procuring Tejas aircraft. About 70% of Tejas weight is carbon fibre. Who made the carbon fibre? The CSIR-NAL. The Tejas lands on naval ships and to be able to land and take off from naval ships, it needs a precise landing and take-off spot. The error cannot be more than half a metre. How do pilots do that? There’s something called a ‘head-up display’ in Tejas aircraft which allows the pilot to make precise take-off and landing. Who made that head-up display? It is the Central Scientific Instruments Organisation in Chandigarh (one of the constituent laboratories of the CSIR)… We can go on citing examples… We collaborate with everybody. When the Rs 48,000 crore order for Tejas was placed, most people lauded the DRDO. Nobody knew that a large amount of technology and the entire control system of Tejas was made by the CSIR. Many people don’t know there is a very glorious collaboration between the CSIR, DRDO and HAL. It is a fault on our part that information has not been distributed among members of the public.
TABASSUM BARNAGARWALA: There is a lot of discussion about how low- and middle-income countries have low Covid-19 mortality rates. Is the ‘hygiene hypothesis’ the only reason behind it or is there a loose link with the BCG vaccination? Or, in India’s case, is there a low recording rate of the deaths?
My personal research paper on the issue is coming out in a journal called Current Science… The population of the United States is roughly one-fourth of India’s. The total number of deaths in the US is more than double that of India. If you take the ratio of people dying per million, it is a highly skewed ratio in the countries which have high GDP or a high Human Development Index. This is true across the world. If you look at the number of people dead in African and Southeast Asian countries, it is way lower than countries with high GDP and HDI. Many people say it is under-reporting, but if you are under-reporting, India would have had to report about eight to 10 times more deaths (in comparison to the US). If we (India) were under-reporting, about one-and-a-half-million people in India would have succumbed to Covid-19. I don’t think anyone believes that one-and-a-half million people in India have died… Under-reporting is not the cause. In Africa, it would have caused havoc. In places like Dharavi, it would have been a catastrophe. But that has not happened.
The second issue that countries with high HDI have is an ageing population. If you look at the life expectancy in such countries, the average age is much higher than countries like ours. And, we know that this virus affects older people more.
Now look at the distribution of other diseases. The incidence of communicable disease like tuberculosis, malaria and cholera in countries which have higher GDP and HDI is much lower. And the incidence of these diseases in low-HDI countries is much higher. On the contrary, non-communicable diseases such as diabetes, asthma, psoriasis are much higher in countries with high HDI and lower in low-HDI countries… In low-HDI countries, the sanitation parameters tend to be poor… It is an established fact that improved sanitation conditions have increased the incidence of auto-immune disorders in higher HDI countries… According to the hygiene hypothesis, as we are continuously exposed to pathogens since our childhood, our immune system is trained… In the paper (in Current Science) we are saying that what has saved us is the immune training our body has got because of continuous exposure (to pathogens) since our childhood.
AMITABH SINHA: This is probably not the last pandemic that we will see. In terms of our response, how is the next pandemic going to be different? What are the things we have learned and institutionalised so that the response to any such pandemic in the future is different and qualitatively better?
Most important is health monitoring infrastructure… In this case, the response was very rapid. As soon as the Chinese authorities detected the cluster of pneumonia-like cases, they reported it to the WHO. By the fourth day, the WHO team was on the ground in Wuhan to assess the situation. On the seventh day, we knew that it was because of a virus called coronavirus… We need to have a rapid action force… And this is good in the country right now… We are doing reasonably well (in our response) and we should try to improve. But what we actually need to improve is infrastructure in terms of safety level facilities. We need to have multiple BSL-4 (biosafety level-4) facilities in the country, where we can take the infectious organism and assess it. We also need to look at zoonosis — many viruses jump from animal to human. We must keep sampling viruses or parasites in animals all the time. It is important to have a surveillance system for animals and potential diseases that could come from many of them.
Lastly, we need to have supply chains and logistics ready for diagnostics, drugs, essential equipment, doctors, nurses, so that if any such contingency arises, we are able to cater to any remote corner of the country within a very short time.
The session was moderated by Resident Editor (Pune) Amitabh Sinha