Mumbai: “Within seven months of recognising that there was an outbreak, we have 30 vaccines that are in clinical trials already. This is fabulous for science,” Gagandeep Kang, professor at the Christian Medical College in Vellore, told IndiaSpend. Kang, a scientist and clinician who built the Indian rotavirus and typhoid surveillance networks, has also worked with the Indian Council of Medical Research.

As many as 165 vaccines, according to the New York Times coronavirus tracker, are being developed around the world. Of these, 32 are in the stage of human trials and two--a Chinese and a Russian vaccine--have been approved in those countries for early or limited use.

In an interview, Kang spoke about vaccines and their efficacy, and why it is important to understand COVID-19 and how it progresses in people.

Edited excerpts:

Where are we currently in the search for a vaccine for COVID-19?

There has been an unprecedented pace of development globally. We have learnt from Ebola. In the case of Ebola, we had a vaccine that was sitting in a freezer but it took us nine months to get all the paperwork in place to begin the evaluation of the vaccine. After that, the world got together and said that we are not going to let that happen again, and that is the reason, why within seven months of recognising that there was an outbreak, we have 30 vaccines that are in clinical trials already. This is fabulous for science. It is also hugely challenging because we are directing a lot of resources towards vaccine development and not necessarily in other measures of control. That is the global scenario.

In India, we also have a lot of vaccine candidates that are being developed by our companies; many of these are in partnership with global players, some of them are being developed indigenously as well.

You mentioned that we are devoting a lot of resources to vaccine development and not enough to controlling COVID-19. Why does it have to be a choice?

It is not really ‘either’ or ‘or’. In an ideal world, you would have enough resources to direct towards all the public health strategies that are important--testing, tracing and isolating. You would have enough resources to treat people who got sick. You would be looking at developing new and easy diagnostics, at repurposing drugs, designing and developing new drugs and prevention through vaccines.

For reasons that are not completely understood, it almost seems like the world thinks that the vaccines are going to be a panacea for everything. Once we have a vaccine, the problem is solved. While I am a huge proponent of vaccines, I know that vaccines are only one part of our ability to handle infectious diseases. So the focus on vaccines is good, but there is a lot more we need to do.

What is your sense of the efficacy of the vaccines rolled out?

We actually have absolutely no knowledge of the efficacy of any vaccine at this time. That is why we do phase III studies, the efficacy studies, to see whether vaccinated people develop less disease than those who are not vaccinated. We are now in multiple phase III trials with multiple products, and we need to wait for the interim and the final results from those trials and then we will have answers.

But given that this is a virus about which we have learnt a lot, given the data that we have from some monkey studies, I think there is a very high likelihood that we will have a successful vaccine in the next six to 12 months. And it is important to remember that having a successful vaccine is only the first step. These vaccines are tried first in young and healthy people. The people who are most affected are the elderly. Will this vaccine work in the elderly, we do not know. The Oxford trial does include a small number of the elderly, but it will not be sufficient to give us efficacy data.

What will a vaccine do and how will it work in the case of COVID-19?

If we were to look at what an ideal vaccine was, it should be a vaccine where I take one shot--preferably it should be a nasal spray so that I do not even have to take the shot--and I am protected from infection for life. I never need to take another booster, I can go out safely, and I know that I will never acquire this infection. Unfortunately, those vaccines are rare; we do not have them for practically any disease that you’d care to name. You do need multiple injections, you might require boosters. It may not work for everybody. It would certainly not work in people who are immunocompromised.

So if you look at what a vaccine does, one way of looking at how we might expect the vaccine to perform is to look at influenza. In the case of influenza vaccines, we have to make a new vaccine every year because these strains change. We need to take the vaccine every year because protection is short-lived, and there is some level of [immune system] memory but it is not huge. In some years the vaccine might not work at all.

We might not see that kind of variation with the coronaviruses. I think we will have an immune response, but we do not know the duration for which people will be protected and whether that protection will be from severe disease or from infection. Lots of people get infected but not everybody gets diseased. So our low bar is that this must prevent the disease. And if we look at what the FDA [Food & Drug Administration], the US regulator, and the WHO [World Health Organization] have recommended, they have said that they will license vaccines that have a 50% efficacy as a point estimate--which means the vaccine, in the trial, should prevent at least 50% of confirmed disease. This is not about infection.

The other element in controlling COVID-19 is cure. Does the cure now appear conceptually so distant that we are putting all our eggs in the vaccine basket?

I think a cure means an anti-viral and we have to remember that in this case, as the disease progresses, it needs different kinds of drugs at different stages. In the early stages, certainly an antiviral would be a good idea. But much of the morbidity and the mortality that we are seeing because of COVID-19 is not any more because of the virus. It is really because the immune system has taken over and is dysregulated. In trying to eliminate the virus, it overshoots and results in multiple consequences that then become difficult to arrest. So understanding the virus, and understanding the disease process in people who are severely ill is very important.

In your mind, what would the cure or the components of the cure be as they are being worked upon right now?

In early disease, we would be looking for an antiviral, so that you do not go on severe disease. Once you are in severe disease, we will be looking for the pathways that are impacted by the viral infection and what you can do about them. For example, remdesivir is an antiviral and we should be evaluating whether we should be using it earlier and earlier in the illness. Dexamethasone is a steroid, and we should be evaluating its role in controlling severe disease. So, whatever the course of infection we are looking at, we need to be looking at evaluating different approaches for modulating mild and severe illness.

From what we know, the disease is fatal in some cases. Even the medicines administered work in some and do not work in others. As you explain it, in situations where the disease has crossed a certain tipping point within the body and the immune system reacts badly, no medicine really works. So is there something that goes beyond COVID-19 itself and is akin to maybe some disease conditions that we have not known?

There are multiple components that you need to look at. One is the effect on the lungs. We know that the lungs in the COVID-19 disease are not like the lungs that you see in the other kinds of pneumonia. The happy hypoxia that people describe--that your oxygen saturation drops without necessarily a person feeling uncomfortable or breathless--seems to be something that we have not seen for other diseases. One of the treatments that we have found for this is something that was known before but was not applied as widely. And that is the ability to increase the oxygenation of the lungs by treating people on their stomachs rather than on their backs. That then works with just room air and it works when someone is being administered additional oxygen through a nasal cannula or a mask. Lung aeration is important.

The second component to look at is the suppression of inflammation, which is what dexamethasone does, and the third component is what is happening with the blood vessels. This is what impacts multiple organ systems in the body, not just the lungs. We now know that low-molecular-weight heparin [an anticoagulant, or blood thinner] can help. So anticoagulation, and the point at which anticoagulation should be used, are things that have been tested and tried only in the last few months. I am hoping that there will be more such experimentation which will lead to better patient survival.

You had mentioned Ebola. What are the two or three things that make COVID-19 different from Ebola?

From the public health point of view, a lot of what you need to understand about diseases is: what is the transmissibility of the disease? Who gets it from whom and how? In Ebola, we knew very clearly that it was person-to-person transmission, you needed to be in contact with the patient to acquire Ebola. So therefore, the reproductive number for Ebola was relatively low. And that is why when we saw an outbreak, the largest outbreak was 30,000 cases.

In the case of SARS-CoV-2, the virus that causes COVID-19, what we are seeing is a virus that spreads through the respiratory route, which means that you do not need to be in direct contact with the person to acquire the infection. And the other big difference is that it spreads when a person is asymptomatic or pre-symptomatic. And that is what is resulting in the high rates of infections that we are seeing here. So from a public health point of view, from the view of what kind of control measures we need to be using, these are two very different disease conditions. Then you come to the clinical picture and then, of course, every disease is different in that context.

We have seen many seroprevalence surveys for Mumbai, Delhi and recently for Pune, which found that 50% of those surveyed had antibodies. What is this broadly telling you?

It is telling us what proportion of people, who are in the areas that were sampled, were exposed to infection. So the presence of antibodies means that you were infected at some point in the past and your body has responded to that. For one, it tells us that in these areas, just counting the cases was insufficient. It can tell us by what factor we were off in the counting of cases.

In the future, when we have a better understanding of what immune responses really mean, it might tell us how long we might be protected from infection. Those are not answers we have yet, but sero surveys will be useful for us to continue to track infection and the potential for populations to be protected from subsequent infections.

Is it giving you comfort that more people perhaps have actually contracted the virus and not been affected by it?

Yes, it does. One of the ways to think about it is, actually in Pune and Mumbai the populations that were selected, were chosen because there were high levels of disease, intermediate levels of cases being reported from those locations. We expected 10% of the population to be affected; and it is actually 50%.

It is a good thing in that it tells us that we might be actually closer to herd immunity than we thought, but you could also look at it as a negative to see what else is out there that we missed that we should try to have a better handle on in the future.

What according to you should be the focus and thrust in the management of this disease?

Your principles stay exactly the same as they were right at the beginning. You should have the opportunity to test as widely and as frequently as you can. And act on the results of those tests rapidly. It is not useful if you do a test today and get the result three or five days or a week from now. It is not useful if you do not have the ability to act on it. What you are trying to do is prevent transmission from an infected person, so that the overall numbers in the community come down. That can happen if we test and we make sure that we isolate quickly. People in contact should obviously be traced and tested as well so that we can bring down the circulation of the virus in the community. We have seen from many examples from around the world that this is feasible but requires a lot of resources. So we have to balance the practical with what is ideal.

The number of COVID-19 cases in India is still rising. Do you think this number will plateau and then start going down over the next three to four months? How alert should we be and until when?

One of the things to remember is that India is a very large country in terms of its population. We also have a range of population density. What we have seen is the most densely populated areas were infected first, now we are at tier-2 cities getting infected. We still have a long way to go. I do not think the pattern of the cumulative numbers is going to change, but where the patterns play out will change as the disease spreads to different parts of the country. It is very difficult to say that we are plateauing… we are not only plateauing, but heading downwards in some places, but we are on the upswing in others.

We welcome feedback. Please write to respond@indiaspend.org. We reserve the right to edit responses for language and grammar.

Mumbai: “Within seven months of recognising that there was an outbreak, we have 30 vaccines that are in clinical trials already. This is fabulous for science,” Gagandeep Kang, professor at the Christian Medical College in Vellore, told IndiaSpend. Kang, a scientist and clinician who built the Indian rotavirus and typhoid surveillance networks, has also worked with the Indian Council of Medical Research.

As many as 165 vaccines, according to the New York Times coronavirus tracker, are being developed around the world. Of these, 32 are in the stage of human trials and two--a Chinese and a Russian vaccine--have been approved in those countries for early or limited use.

In an interview, Kang spoke about vaccines and their efficacy, and why it is important to understand COVID-19 and how it progresses in people.

Edited excerpts:

Where are we currently in the search for a vaccine for COVID-19?

There has been an unprecedented pace of development globally. We have learnt from Ebola. In the case of Ebola, we had a vaccine that was sitting in a freezer but it took us nine months to get all the paperwork in place to begin the evaluation of the vaccine. After that, the world got together and said that we are not going to let that happen again, and that is the reason, why within seven months of recognising that there was an outbreak, we have 30 vaccines that are in clinical trials already. This is fabulous for science. It is also hugely challenging because we are directing a lot of resources towards vaccine development and not necessarily in other measures of control. That is the global scenario.

In India, we also have a lot of vaccine candidates that are being developed by our companies; many of these are in partnership with global players, some of them are being developed indigenously as well.

You mentioned that we are devoting a lot of resources to vaccine development and not enough to controlling COVID-19. Why does it have to be a choice?

It is not really ‘either’ or ‘or’. In an ideal world, you would have enough resources to direct towards all the public health strategies that are important--testing, tracing and isolating. You would have enough resources to treat people who got sick. You would be looking at developing new and easy diagnostics, at repurposing drugs, designing and developing new drugs and prevention through vaccines.

For reasons that are not completely understood, it almost seems like the world thinks that the vaccines are going to be a panacea for everything. Once we have a vaccine, the problem is solved. While I am a huge proponent of vaccines, I know that vaccines are only one part of our ability to handle infectious diseases. So the focus on vaccines is good, but there is a lot more we need to do.

What is your sense of the efficacy of the vaccines rolled out?

We actually have absolutely no knowledge of the efficacy of any vaccine at this time. That is why we do phase III studies, the efficacy studies, to see whether vaccinated people develop less disease than those who are not vaccinated. We are now in multiple phase III trials with multiple products, and we need to wait for the interim and the final results from those trials and then we will have answers.

But given that this is a virus about which we have learnt a lot, given the data that we have from some monkey studies, I think there is a very high likelihood that we will have a successful vaccine in the next six to 12 months. And it is important to remember that having a successful vaccine is only the first step. These vaccines are tried first in young and healthy people. The people who are most affected are the elderly. Will this vaccine work in the elderly, we do not know. The Oxford trial does include a small number of the elderly, but it will not be sufficient to give us efficacy data.

What will a vaccine do and how will it work in the case of COVID-19?

If we were to look at what an ideal vaccine was, it should be a vaccine where I take one shot--preferably it should be a nasal spray so that I do not even have to take the shot--and I am protected from infection for life. I never need to take another booster, I can go out safely, and I know that I will never acquire this infection. Unfortunately, those vaccines are rare; we do not have them for practically any disease that you’d care to name. You do need multiple injections, you might require boosters. It may not work for everybody. It would certainly not work in people who are immunocompromised.

So if you look at what a vaccine does, one way of looking at how we might expect the vaccine to perform is to look at influenza. In the case of influenza vaccines, we have to make a new vaccine every year because these strains change. We need to take the vaccine every year because protection is short-lived, and there is some level of [immune system] memory but it is not huge. In some years the vaccine might not work at all.

We might not see that kind of variation with the coronaviruses. I think we will have an immune response, but we do not know the duration for which people will be protected and whether that protection will be from severe disease or from infection. Lots of people get infected but not everybody gets diseased. So our low bar is that this must prevent the disease. And if we look at what the FDA [Food & Drug Administration], the US regulator, and the WHO [World Health Organization] have recommended, they have said that they will license vaccines that have a 50% efficacy as a point estimate--which means the vaccine, in the trial, should prevent at least 50% of confirmed disease. This is not about infection.

The other element in controlling COVID-19 is cure. Does the cure now appear conceptually so distant that we are putting all our eggs in the vaccine basket?

I think a cure means an anti-viral and we have to remember that in this case, as the disease progresses, it needs different kinds of drugs at different stages. In the early stages, certainly an antiviral would be a good idea. But much of the morbidity and the mortality that we are seeing because of COVID-19 is not any more because of the virus. It is really because the immune system has taken over and is dysregulated. In trying to eliminate the virus, it overshoots and results in multiple consequences that then become difficult to arrest. So understanding the virus, and understanding the disease process in people who are severely ill is very important.

In your mind, what would the cure or the components of the cure be as they are being worked upon right now?

In early disease, we would be looking for an antiviral, so that you do not go on severe disease. Once you are in severe disease, we will be looking for the pathways that are impacted by the viral infection and what you can do about them. For example, remdesivir is an antiviral and we should be evaluating whether we should be using it earlier and earlier in the illness. Dexamethasone is a steroid, and we should be evaluating its role in controlling severe disease. So, whatever the course of infection we are looking at, we need to be looking at evaluating different approaches for modulating mild and severe illness.

From what we know, the disease is fatal in some cases. Even the medicines administered work in some and do not work in others. As you explain it, in situations where the disease has crossed a certain tipping point within the body and the immune system reacts badly, no medicine really works. So is there something that goes beyond COVID-19 itself and is akin to maybe some disease conditions that we have not known?

There are multiple components that you need to look at. One is the effect on the lungs. We know that the lungs in the COVID-19 disease are not like the lungs that you see in the other kinds of pneumonia. The happy hypoxia that people describe--that your oxygen saturation drops without necessarily a person feeling uncomfortable or breathless--seems to be something that we have not seen for other diseases. One of the treatments that we have found for this is something that was known before but was not applied as widely. And that is the ability to increase the oxygenation of the lungs by treating people on their stomachs rather than on their backs. That then works with just room air and it works when someone is being administered additional oxygen through a nasal cannula or a mask. Lung aeration is important.

The second component to look at is the suppression of inflammation, which is what dexamethasone does, and the third component is what is happening with the blood vessels. This is what impacts multiple organ systems in the body, not just the lungs. We now know that low-molecular-weight heparin [an anticoagulant, or blood thinner] can help. So anticoagulation, and the point at which anticoagulation should be used, are things that have been tested and tried only in the last few months. I am hoping that there will be more such experimentation which will lead to better patient survival.

You had mentioned Ebola. What are the two or three things that make COVID-19 different from Ebola?

From the public health point of view, a lot of what you need to understand about diseases is: what is the transmissibility of the disease? Who gets it from whom and how? In Ebola, we knew very clearly that it was person-to-person transmission, you needed to be in contact with the patient to acquire Ebola. So therefore, the reproductive number for Ebola was relatively low. And that is why when we saw an outbreak, the largest outbreak was 30,000 cases.

In the case of SARS-CoV-2, the virus that causes COVID-19, what we are seeing is a virus that spreads through the respiratory route, which means that you do not need to be in direct contact with the person to acquire the infection. And the other big difference is that it spreads when a person is asymptomatic or pre-symptomatic. And that is what is resulting in the high rates of infections that we are seeing here. So from a public health point of view, from the view of what kind of control measures we need to be using, these are two very different disease conditions. Then you come to the clinical picture and then, of course, every disease is different in that context.

We have seen many seroprevalence surveys for Mumbai, Delhi and recently for Pune, which found that 50% of those surveyed had antibodies. What is this broadly telling you?

It is telling us what proportion of people, who are in the areas that were sampled, were exposed to infection. So the presence of antibodies means that you were infected at some point in the past and your body has responded to that. For one, it tells us that in these areas, just counting the cases was insufficient. It can tell us by what factor we were off in the counting of cases.

In the future, when we have a better understanding of what immune responses really mean, it might tell us how long we might be protected from infection. Those are not answers we have yet, but sero surveys will be useful for us to continue to track infection and the potential for populations to be protected from subsequent infections.

Is it giving you comfort that more people perhaps have actually contracted the virus and not been affected by it?

Yes, it does. One of the ways to think about it is, actually in Pune and Mumbai the populations that were selected, were chosen because there were high levels of disease, intermediate levels of cases being reported from those locations. We expected 10% of the population to be affected; and it is actually 50%.

It is a good thing in that it tells us that we might be actually closer to herd immunity than we thought, but you could also look at it as a negative to see what else is out there that we missed that we should try to have a better handle on in the future.

What according to you should be the focus and thrust in the management of this disease?

Your principles stay exactly the same as they were right at the beginning. You should have the opportunity to test as widely and as frequently as you can. And act on the results of those tests rapidly. It is not useful if you do a test today and get the result three or five days or a week from now. It is not useful if you do not have the ability to act on it. What you are trying to do is prevent transmission from an infected person, so that the overall numbers in the community come down. That can happen if we test and we make sure that we isolate quickly. People in contact should obviously be traced and tested as well so that we can bring down the circulation of the virus in the community. We have seen from many examples from around the world that this is feasible but requires a lot of resources. So we have to balance the practical with what is ideal.

The number of COVID-19 cases in India is still rising. Do you think this number will plateau and then start going down over the next three to four months? How alert should we be and until when?

One of the things to remember is that India is a very large country in terms of its population. We also have a range of population density. What we have seen is the most densely populated areas were infected first, now we are at tier-2 cities getting infected. We still have a long way to go. I do not think the pattern of the cumulative numbers is going to change, but where the patterns play out will change as the disease spreads to different parts of the country. It is very difficult to say that we are plateauing… we are not only plateauing, but heading downwards in some places, but we are on the upswing in others.

We welcome feedback. Please write to respond@indiaspend.org. We reserve the right to edit responses for language and grammar.



COVID-19: Hundreds Of Clinical Trials Under Way In India, Many Lack Rigour, Say Experts

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