As India begins to ease lockdown restrictions in districts classified as green and orange zones (which have seen fewer COVID-19 cases), we will need to maintain a certain degree of self-imposed discipline--such as physical distancing, hand hygiene and the use of masks--for quite some time, K Srinath Reddy, president, Public Health Foundation of India, says.

The lockdown has helped our health system and social systems become better prepared to deal with the pandemic, said Reddy, an adjunct professor of epidemiology at Harvard University and formerly the head of department of cardiology at the All India Institute of Medical Sciences. As we get back to work, the way we move on the streets and the way we work will all change, and we are now better prepared for the change, he said.

The West has not seen such a scenario--surging infections, flooded hospitals and ventilator shortage--in many years, and this vulnerability has shaken them to the core, Reddy said, adding that as a result, we are going to see a much more intense effort to fight COVID-19 than in the area of neglected tropical diseases, for example.

Edited excerpts:

The first question really is, can I get back to work on May 4?

Well, [that] depends upon which zone in India you are living in. If you are living in a red zone, your movements are going to be greatly restricted; if you are living in a green zone, then certainly you can get back to work. Even in a red zone, a number of areas of work are likely to be resumed, but with [a] great deal of care. The important element is that a lockdown is an extreme form of isolation. Now, when you get back to [the] post-lockdown phase, then you are going to be in a sort of self-imposed discipline of social distancing (better called physical distancing), plus personal hygiene, which means handwashing and possibly masks.

So, the important thing is, if you are in a zone where the intensity of the viral transmission is considered to be low, the restrictions are going to be less in the nature of occupations, though some of these other restrictions will continue. On the other hand, if you are in a high-intensity zone, the number of occupations that are going to be permitted will probably be fewer and be restricted only to the very essential ones. And as the intensity comes down, that list will grow and possibly people can ease back into more areas of work and social activity.

Almost 78% of those who have died of COVID-19 in India had comorbidities, and almost 49% patients are young, as opposed to a much lower percentage earlier. So, things are fundamentally changing. Not only is it getting localised as you pointed out, but also the nature of the disease and the way it has spread in the last month seems to have changed.

We have to differentiate between the people who have died, and the people who are getting infected. Secondly, when we talk of rates, it is very important for us to recognise that a rate is essentially the number of persons diagnosed as a fraction of the number of tests performed. If you increase the number of tests, then you are obviously going to detect more cases. You always need to compare the ratio rather than just look at the number of cases being reported.

Having said that, it is not unusual for young people to get infected, because they are usually more socially mobile. But in general, the clinical severity is much less, and fatal outcomes are very uncommon unless they have a co-existing disease. Or unless they have had marked repetitive exposure to the virus. That is why we are seeing sometimes, unfortunately, some of the younger healthcare providers also having serious infections because of repetitive exposure. So, by and large, it is the older people and the people with comorbidities who are affected.

You talked about the proportion of cases. India is seeing around 4.5%-5% positives to tests. Is that a figure that, you feel, reflects the true picture?

We do not really know because these are based on the kinds of tests that are being performed and the indications for the tests. People are beginning to recognise that there are a large number of asymptomatic people who might not have been tested. In other countries, we are seeing that when you are applying the antibody test--which, of course, does have some false positives--or if you are applying the antigen test much more widely, you are seeing a fair number of asymptomatic people. Even in the ICMR [Indian Council of Medical Research] series, there were a large fraction of people who were asymptomatic at least at the time of testing. So, if there are a large number of people who have been infected but never been detected, then the percentages would change obviously.

I believe overall, when all the data are in, we will find that this highly infectious virus has been less virulent than has been feared, and the main fear has arisen because of the rapidity of the spread, which resulted in a huge surge of cases at once. But whenever it is all done and over with, we will be able to get all the data and then we will be able to say it was not as bad as feared, but it did hit us with a suddenness we could not cope with.

I was interviewing Jay Bhattacharya at Stanford, who has been among those who have been arguing that the spread of this disease is far wider than what we believe. So, if that is the case, how should we in India interpret that, as we get back to or try to get back to work?

Yes, I agree with that; the virus is likely to have spread far more. The US, of course, did antibody testing, and that has its own false positives. I would not entirely go by the numbers that came from California. However, I certainly believe that the virus does spread much faster and wider than we are currently figuring it out in India. However, most of these are likely to be asymptomatic or mildly symptomatic. We can get back to work. But still, in order to protect ourselves and protect others, we do need to keep our physical distancing, masks, and handwashing, because we do not want to carry the virus back, even if we are relatively untouched in terms of physical effects. We do not want people who are older, people who have comorbidities, to succumb because we were careless.

But what do you intuitively or clinically understand or have concluded from this disease and its spread so far, and the manner in which it has manifested itself in patients in India? Are we likely more immune than other parts of the world? Are we experiencing a different strain of this virus? Or is there any other factor, like temperature, which is causing it to be more diminished in its efficacy? Are there any other factors at work or likely at work?

I believe, firstly, our demography has been our great asset--we have a much younger population. Secondly, we also have a rural population where the mobility is much less; the transmission of the virus from foreign-returned travelers or their immediate contacts is much less; and therefore, unless we allow for a huge amount of urban travel to rural areas, or rural travel to urban areas, you are not going to see the virus spread very widely in the rural areas. So that is going to be a large protected area. You cannot just apply statistics from Italy or China to the entire Indian population without taking into account this demographic fact.

I believe we also have some benefit in terms of the temperature. The weather is probably likely to play in our favour, particularly as the temperatures rise and even humidity sets in. Whether the other factors like BCG immunisation (bacille Calmette-Guérinmalaria, against tuberculosis), polio immunisation--which has also been recently invoked as a general immunity booster--are operating or not, we cannot really say with confidence. All we can say is that these are hypotheses that can be examined. They are not evidence at the moment. They are hypothesis-generating, not hypothesis-testing. Certainly, as far as BCG is concerned, some trials have started globally, and also in India, some studies have been initiated.

To come to the curve question, is this a flattening or blunting of the curve?

Well, as I said, you can really talk about the shape of the curve when you standardise for the number of tests that are being performed and the criteria for performing the tests. If your criteria are expanding, or if your numbers of tests are expanding, naturally you are going to be detecting more. Unless you standardise for that, you really cannot comment about the curve. But having said that, with the criteria becoming more liberal and more tests being performed, if we are seeing the doubling time actually widening and the curve actually moving to a lower slope, I believe that is a positive sign.

Let us say, maybe I am in a red zone where things are likely to be stretched for a little longer, but for those who are not, they have to be mentally ready for the fact that they will be exposed to the virus and quite likely will contract it. To that extent, what has really changed in the last one month, except for the fact that we are obviously more prepared to handle this challenge than we were earlier?

Firstly, our health system is better prepared. To some extent, our social systems are better prepared. Thirdly, we are a little better prepared. I believe that lockdown is a form of imposed discipline--pretty severe at that. But now, we have to move into a lot of personal discipline. It is something that we have to adopt as a matter of daily routine for some time to come. So even in the green zone, that is what is changing. While we may be getting back to work, the way we work with our colleagues in the office, the way we move on the streets--all this is going to change. And this is, I think, a time we have been prepared for the change.

There is a lot of research going on, on vaccines. There is one Indian company saying that something is likely to be ready by October. How are you looking at all the headlines from that world?

I believe the group of researchers in Oxford are saying that they will have a vaccine available by September. Of course, the trials which have just started first have to show efficacy and safety. Assuming that they do, now manufacturers are already getting ready for large-scale manufacture. We know one Indian manufacturer, Serum Institute, which has already placed advance payments to get access to the vaccine and prepare for several million doses of the vaccines. There are, of course, going to be a number of other global competitors, who are also racing towards vaccine preparation. If we are lucky, we will get a vaccine available and tested by September.

But even then, mass production and dissemination across the world--particularly in view of the kind of global demand that we will have--means that we will probably take about a year. Of course, if we [India] actually get the manufacturing rights--because we have a great potential, we can produce at low cost, at high volume--then, it is possible that even earlier than that, our population may stand to benefit. But I think we should plan for about a year before we see mass immunisation.

One of the criticisms seems to be that vaccines may come out, but if you look at what had happened during AIDS, for instance, there were a lot of vaccines that looked like they had emerged, but did not finally work. And obviously a lot of expectations were dashed. Are people ready for that? There has to be a hit-and-miss in this, which maybe people are not prepared for, even when it comes to COVID-19.

Obviously, when there is a fair amount of panic and apprehension about something that was projected as a mass killer, people have high hopes and look forward to a saviour. We have to be ready--when we are coming to actually experimental biology and the area of vaccinology--that we may have some failures. But right now, at least the Oxford team seems fairly confident--based on their prior work with coronaviruses--that they have a winner at hand. We will have to wait and see.

Fortunately, there are at least two Chinese trials going on, two trials going on in Europe, and some trials going on in the US, and some vaccine development efforts have been initiated in India as well. Therefore, we are going to have several candidates coming up in the next few months, and possibly the trials being completed over the course of the next one year. So, we should hope for at least one of them to turn out to be a winner.

As a global public health professional, are you getting a sense that the momentum that we are seeing behind it--compared to the Ebola or the SARS virus--that there is so much sheer brain power, and engine power going into this, that some solution must emerge only because we are putting in so much effort and it should convert very soon?

Yes, I think that is because the West has never been threatened like this ever before. Other than HIV, where also they managed fairly well early on, most of the other large epidemics, zoonotic epidemics in particular, have hit other parts of the world. This level of zoonotic epidemic with such surges in infections, and hospitals being flooded with cases, ventilators not being available, the West has never seen this in so many years. So, there is a fair amount of money as well as brain power being put behind this effort. It is that level of vulnerability that has shaken them to the core, and therefore we are going to see a much more intense effort than in the area of neglected tropical diseases, for example.

On medicines, I know the ICMR has prescribed an approach. Most doctors across the country are following that approach of using hydroxychloroquine, retrovirals, or steroids, depending on the condition of the patient. But what is your sense, on what the current medicine and medical approach is? Could there be some sort of medical--cure is too positive a word--some sort of positive intervention?

Well, a lot of trials are going on with a number of candidate drugs in different parts of the world, for treatment as well as for prevention. Now, in terms of treatment, it depends upon whether you have a properly randomised trial or not--that means, whether you have a proper comparison arm. Secondly, what are the outcome measures? Are you only going to be only looking at the viral load? Or are you going to be looking at deaths? Or are you going to be looking at the days to recovery from a very severe pulmonary or other infection? So, the whole idea is to try and get drugs which are likely to be reducing the number of deaths, with a clear-cut impact on mortality.

Next, at least, in terms of having a clear-cut impact on reducing the severity of the illness in terms of reducing the time taken for recovery, if you are only looking at the viral load, you may be misled. Now, therefore the trials have to be large enough in order to assess this. That is why the World Health Organization’s (WHO) Global Solidarity Trial is looking at different arms, hoping for sample sizes that are large enough across the countries, so that these very definitive hardened points can be assessed.

Now, there have been a couple of trials that have come up in the last couple of days. In one of them, they have looked at a particular antiviral drug, remdesivir. They have looked at whether a five-day course is adequate, as good as a ten-day course. But that does not have a comparison arm, it is only looking at the duration. And it does not tell you whether the deaths would have been lower compared to some other drug or no drug at all.

Then, there is another trial, which has been publicized with much larger numbers, where the same drug in a randomised control trial has shown that it is actually having an impact on reducing the number of days of severe illness. But it did not show any impact on the deaths, because possibly the numbers were not large enough. So we do have several questions still to be answered, and that is why you need the kind of studies that are being done under the WHO with a large enough number of patients recruited from across the world, so that we can provide more definitive answers, rather than providing half answers and half questions unanswered.

As we get back to work or want to get back to work, what is your advice to citizens, public health professionals or medical professionals who will watch this?

We are so used to moving around freely, and having fun and frolic apart from everything else. We can still do that, but in different ways. I think we have to recognise that there are three elements of protection that are required--physical distancing, masks, and hand hygiene. We have to maintain this for quite some time in public--at least, the masks are going to be required. And that is necessary not only to protect ourselves, but to protect our colleague workers as well as our family members. So a certain degree of self-imposed discipline is going to be required, but that does not mean we should not socialise with others in the best possible manner. It is not that we have to live with a doomsday scenario all the time. I think we should have fun, we should socialise to reduce the social disconnect, but we should do it in a different way.

In fact, we commune with nature also much more intimately now--we hear the bird calls, we have visitors to our backyards, so there is so much to do. If nothing else, being in Delhi and Gurgaon seeing the blue sky, breathing unpolluted air is such a boon that sometimes this does not seem to be a punishment at all.

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