scorecardresearch
Follow Us:
Friday, November 27, 2020

The Sandip Roy Show

What makes people tick? What are the stories they carry with them? In a world of shouting heads, veteran journalist, radio commentator and novelist Sandip Roy sits down to have real conversations about the fascinating world around us and the people who shape it. Catch these engaging interviews every other Sunday

Episode 62 November 1, 2020

Why life won’t go back to normal even after a COVID-19 vaccine, with Dr Gagandeep Kang

As the COVID-19 pandemic continues to rage on, a lot of people remain hopeful for a vaccine. And right now several vaccines are in the works. But how will we know which is the right one? How effective will it be? Will there be enough for all of us? And will we be able to stop social distancing then? To answer these questions and more, Sandip speaks to Dr Gagandeep Kang, microbiologist and professor at the Christian Medical College in Vellore. Dr Kang is credited with pioneering work on an indigenous Rotavirus vaccine, and is the the first Indian scientist to be elected fellow of The Royal Society.
Transcript:
Sandip Roy
Recently we heard that India has crossed its COVID peak in September. But then this week the global tally of COVID-19 cases jumped up by more than 500,000. That’s a one day increase record since the beginning of the pandemic, and Europe is preparing to go for a shutdown again. But there are vaccines in the works. Several. I don’t know about you but the more options I get, the more confused I become. How do we know which is the right vaccine? Will we have enough? If there’s a 50% efficacy rate then how confident can I be that I’m protected, even if I have the vaccine? And when can I take off my mask and hug a friend again?

So this week we reached out to Dr Gagandeep Kang, microbiologist and professor at the Christian Medical College in Vellore, who is credited with pioneering work on an indigenous Rotavirus vaccine. And is the first Indian scientist to be elected fellow of The Royal Society.

Dr Gagandeep Kang, welcome back to the show.

Dr Gagandeep Kang
Thank you, Sandip. I’m happy to be here.

Sandip Roy
Well, vaccines are on everyone’s mind these days. So where are we now?

Dr Gagandeep Kang
Well, we have 321 vaccine projects ongoing around the world. We have over 40 vaccines that are being tested in humans and over a dozen that are in phase three efficacy trials.

Sandip Roy
If you were a betting woman, are you more optimistic about one of the other?

Dr Gagandeep Kang
I’m not more optimistic about one particular candidate over any others. I think the readouts that we’ve had so far from the phase one and phase two studies are showing us that all of the vaccines that have been evaluated are safe and immunogenic. But safe and immunogenic does not necessarily mean effective in preventing disease and that’s the outcome that we will get from the Phase three trials. Given that we have a dozen plus candidates that are in phase three. I think it’s very likely that we will have several successful candidates. The question will be, when will we know this and how effective will they be.

Sandip Roy
Does this mean that the different vaccines would produce different levels of immunity?

Dr Gagandeep Kang
That’s correct. So if we look at immunogenicity, the vaccines that we’ve had in the market so far, all the routine vaccines that we take, usually we look to see whether they are producing antibodies, which comes from the adaptive immune system.

When you get infected or you get vaccinated, the body recognises that as foreign and produces antibodies against it. So that is an arm of the adaptive immune system that’s called Humoral immunity. In this case and with a few other vaccines that have been tried before, we also look at another arm of the immune response, which is called Cell-mediated immunity. And in Cell-mediated immunity, you see what is the quality of the immune response, do you generate memory, and also whether there is a chance whether this vaccine might go down the wrong way, creating a response that might be harmful at some point in the future. So with all of the vaccines that are being developed, both arms of adaptive immunity, the Humoral arm and the Cell-mediated are being evaluated.

Sandip Roy
So I’ve been reading things where it says the vaccine, like Covaxin, is apparently about 60 percent efficient. But what people think Oxford is also similar, but above what level of or what level of efficacy would we need in a vaccine to eliminate the need for social distancing and masks?

Dr Gagandeep Kang
You’d need a perfect vaccine and you would need to vaccinate everybody in the world. So when you say that Covaxin and the University of Oxford vaccine are 60 percent efficacious, actually, they’re not. We don’t have that information. What we do have information on so far is only on the immune responses that have been generated in the phase two trials. And we are waiting for the results of the phase three.

The way the trials are set up, the University of Oxford and Bharat Biotech cannot tell you that the vaccine is 60 percent efficacious because they are blinded. They don’t know who has received the vaccine, who has received the comparator, or the placebo.

Sandip Roy
So from a public health perspective, when the WHO says a COVID-19 vaccine should be at least 50 percent effective to be approved, do you think that benchmark is good enough or is actually low?

Dr Gagandeep Kang
There is practically no vaccine that is 100 percent efficacious. Some of the best vaccines we have, like measles, are 90 percent plus. The malaria vaccine that has only about 30 percent efficacy. So while we would all like a perfect vaccine, sometimes we have to work with vaccines that are less than perfect. And the 50 percent efficacy is actually not too bad for a respiratory virus. Most of the influenza vaccines that we use vary from year to year from not working at all to having 60- 65 percent efficacy against certain strains.

What WHO has set as a benchmark and the FDA has done exactly the same as well, is to say that we need a 50 percent point estimate of efficacy. Which means that in the trial, it must be 50 percent. But around that 50 percent, which is the result from the trial setting, is an understanding that when we use the vaccine in other populations, larger groups, we may not find exactly the same result. So 50 percent is the middle of a range. And that range for both FDA and WHO is a minimum level of 30 percent protection. So though we will get an estimate of 50 percent in the trial, actually, the true efficacy of the vaccine may be anywhere from 30 percent to 70 percent.

Sandip Roy
So in that case, to go back to the original question, if it’s true impact is about 30 percent, we will still be needing to practice social distancing and masks and all of those things we are doing now?

Dr Gagandeep Kang
Absolutely, because until we have something that can act as a readout to know whether a person is protected or not. This is called a correlate of protection. It may be an antibody level. We won’t know for sure among all the people who have received vaccine, which ones are protected and which ones are not. So life is not going to go back to normal the minute we have a vaccine. We will continue to need to be careful the same way that we are doing now.

Sandip Roy
Damn, just ruined…

Dr Gagandeep Kang
I’m sorry, I’m not bringing good news for you but this is real life and, you know, public health. But the vaccine will be a game changer because what will happen is that infection will slow down, will stop spreading so quickly because the bulk of people will then be protected. So we will see less severe disease in hospitals and we will reach a stage where our testing and tracing will allow us to handle the disease much, much better. So if we look at Taiwan, for example, right now, because they have outstanding testing and tracing, they’ve gone two hundred days without having a case. All the cases currently are imported.

Sandip Roy
So the other thing I keep reading about, and I would love to have you explain it in lay terms, is this thing about the virus’s basic reproduction number and what it represents. Do we know this number for COVID? And what does it mean in terms of vaccine development?

Dr Gagandeep Kang
So we have a sense of this number and it’s somewhere between 2 and 3.

Sandip Roy
One case can infect two to three people?

Dr Gagandeep Kang
Exactly. So if you have a completely susceptible population, nobody’s ever been infected before, then each person who gets an infection is estimated to spread it to two or three other people. The problem is that this assumes that everybody uniformly comes in contact with three people, and those three people, among all those that you come in contact with, will be uniformly susceptible to getting infected and developing disease.

We know that that is not the case. There is variation in all humans, in all societies. And as long as this 2 to 3 is maintained, as long as there is anything above 1, that means that the overall number of people acquiring infections will continue to grow. If you can bring it down below 1, then that is a disease that will die out in that population, as has been shown in Taiwan.

So with everything that we do, social distancing, masking, we are already modifying R (Reproduction). But a vaccine will help us do that even better. It’s been estimated that masks themselves reduce infections by somewhere between 20 and 40 percent. Now, if you had a vaccine that is 50 percent efficacious, you’re pretty much getting into the range of getting your R below 1.

Sandip Roy
Since you brought up masks, here’s one burning question people had. Initially, people said, ‘Oh masks, if you wash them, then they become useless’. Then I keep seeing ads for reusable masks. People say you can use a mask 30 times at least. What’s the deal with safe practice when it comes to masks?

Dr Gagandeep Kang
So the best masks are the ones that stop the least particles going out and coming in, and these have numbers attached to them. 99, 95, 90, etc. And then you have the regular surgical masks, the blue and green ones that have multiple layers and can have your loops or ties. And then you have the various reusable cloth masks.

Now, if you look at an order, the best masks are the rated masks, and those can be reused with stabilisation in between. And usually this is done in a facility that can do the sterilization. You can use ethylene oxide gas. Some people use ultraviolet radiation, but those masks are supposed to be disposable, but can be used, reused a few times.

If you look at the surgical masks, those should be disposed off, they should not be reused and they should be disposed of as infectious waste. Now, if you look at cloth masks, reusable masks, those can definitely be reused. The most important thing about masks is to make sure that when you wash and dry them, they are really dry. If you put them out in the sun so much better because you’re getting temperature, UV-rays and drying all at the same time, which makes sure that you are removing any infectious material from the masks.

In terms of efficacy, obviously, cloth and reusable masks are the least effective, but even they used appropriately do stop a large proportion of the large droplets that can transmit the virus. They are less effective against the smaller droplets or aerosols, but still reduce the numbers that are either put out or can come in.

So whatever you do, this using masks is a good idea. Reusing masks, for the N 95s, and N 99s, that requires professional sterilizations. Surgical masks, not to be reused. Cloth masks and bought reusable masks can be reused, but make sure that after every use, clean them and make sure they are absolutely dry before you reuse them.

Just because it’s a reusable mask, don’t use it for three days and then wash.

[Ad Break]

Sandip Roy
Now to go back to the vaccine. So the government has said that 25 crore people will be inoculated by July 2021. From a public health perspective, is it wise to give out a date like that in advance of, you know, before there’s actually even a vaccine out there?

Dr Gagandeep Kang
I think the reason that the government has done that is to provoke planning. And make sure that they have internal deadlines for themselves to be ready. Remember, this is going to be something we have never done before. We’ve never had campaigns to immunise adults across the country before. We’ve never had a campaign that not only did not target all adults, but targeted only the elderly. We’ve never had a campaign that targets by occupation.

Will it work by June 2021? I don’t know. I don’t know if we’ll have five hundred million doses available to India to immunise two hundred and fifty million people by June of 2021. The global estimate that’s come from CEPI is that the entire globe will have between two and four billion doses by the end of 2021 across a range of platforms.

India having five hundred million is predicated on an Indian product being successful and having that level of manufacturing capacity as well as getting supply from other parts of the world. So there’s a lot of ifs and buts in there, but it demonstrates that there is a commitment to deliver.

Sandip Roy
But is there going to be a need to actually inoculate twenty five crore people, or is the way vaccines work is you, sort of, build a ring of fire around the most vulnerable, for example, health care workers?

Dr Gagandeep Kang
So it depends on what the goals of your vaccination program are. If the goal is to prevent severe disease and mortality, then the first thing that you do is to try and protect those who are most susceptible.

And that would be really the elderly and those with comorbidities. That’s not a ring of fire strategy, that’s actually treating those people directly. Preventing disease in them. But we don’t know yet whether all of the vaccines that we are making, are going to protect the elderly, are going to protect those with comorbidities. We need those studies to be done.

So if we have priority populations, then one is preventing disease and then preventing infection in those who are most at rise. Which is what you highlighted, health care workers, because they are constantly exposed to the virus. But also there is a responsibility of reciprocity. These are people who are putting themselves at risk to look after potential patients and therefore they need to be protected. This also applies to other health frontline workers. So it does require a strategy because there isn’t going to be enough vaccine for everybody.

Sandip Roy
But even among health care workers, we are going to have to make priority choices, right? I mean, should a ward boy in a hospital have prioritised access to a vaccine before, say, a specialist surgeon?

Dr Gagandeep Kang
I think we should stratify on the basis of risk. So definitely I would prioritise the word boy over, let’s say, a clerk who sits in the office of a surgical unit. But the surgeon is also at risk because he’s operating on potentially infected patients.

Sandip Roy
And now this idea that everybody’s been talking about, herd immunity. It’s something we’ve all learned recently. Your profession knows about this for a long time. How realistic is this idea of herd immunity?

Dr Gagandeep Kang
I think herd immunity is a well-known phenomenon for infectious diseases, but a lot depends on how infectious that agent is and it depends on the duration for which an infected person is protected against reinfection.

So if we take measles as an example, measles is the very, very, very infectious disease, which means that you need for the bulk of the population to be protected against measles, for herd immunity to be achieved. For measles to stop spreading within that community. It’s been estimated that for measles, we need 95 percent of the population to be either infected or vaccinated in order to achieve herd immunity. And that happened in places like the US, the UK. But as soon as vaccination rates dropped, then we saw a resurgence of measles in those countries.

If we look at other diseases that are not as infectious, you can achieve herd immunity at lower levels of exposure in the population. So, for example, the idea of smallpox. You had mentioned that you have this ring of fire. Ring vaccination was actually used to contain smallpox by making sure that people who came in contact with infected individuals were vaccinated and did not spread disease further. So it didn’t require for as much of the population to be exposed, infected or vaccinated to stop transmission of smallpox

The second point I brought up was the duration of protection. For common cold viruses, the adenoviruses, the coronaviruses that cause common colds, the duration of protection can last for months or a few years. Which means that if you are relying on a vaccine to protect, then you might need to give the vaccine very frequently to maintain the levels of immunity that are required in the herd for protection. We’ll just have to wait and see how long protection from vaccination or infection lasts in the case of Sars-COV-2.

Sandip Roy
Well, that’s an area of some confusion. I was just reading in Science magazine that you retain antibodies for at least 5 months. But then I read this other study in L.A. which found that people with mild cases of covid-19, their antibodies against it dropped sharply over the first 3 months after the infection, and it decreased by roughly half every 36 days. So at that rate, the antibodies would disappear within 6 months or a year, wouldn’t it?

Dr Gagandeep Kang
Well, this is confusion confounded, isn’t it?

Sandip Roy
Yes, it is!

Dr Gagandeep Kang
And the reason for that is that every study that we’ve seen so far measures different things. So in the early stages of an epidemic, everybody is trying to get all the information that they possibly can. And if we look at antibody responses, the virus has many different proteins. And when a virus infects human beings, we will make antibodies against all of the viral proteins. Some of them matter. Some of them are just signatures that the virus was there. So these will last for different periods of time. And the tests that we develop to measure these antibodies can also vary.

So are we really measuring in every study the most important proteins for protection from infection? We don’t know. Additionally, these are only antibodies. There are also the cellular immune responses, the T cells, which are important in determining protection from infection. And there are studies that show even if you have a mild or asymptomatic infection, you do make responses that are cell based and those can potentially either give you protection or modify the severity of disease if you get infected.

Sandip Roy
So in that case, the cell sort of retains a memory of the disease and how to fight it. But if I have a mild infection or I’m asymptomatic, does that mean I will have fewer antibodies and that a few months from now the chances are I will have no antibodies?

Dr Gagandeep Kang
It’s possible that you may have no measurable antibodies after a few months, that still doesn’t mean that you are not protected because then we should be looking at what kinds of T cells you have and whether they recognise the virus or not. So your highest level of antibodies is after you’ve just seen the infection and it comes down after a while. But having once been exposed to an infection, the second time your response is much quicker. And that’s because you are retaining memory and the cells, the memory cells, will kick off much faster when they see the virus the second time.

Sandip Roy
So someone who’s had COVID and recovered, or maybe they had a mild case and they’re fine now, what should they be doing? Because there is also a sense of complacency where people feel like, ‘OK, I’ve got it, I’m done with it’.

Dr Gagandeep Kang
It’s important to remember that this is a mucosal infection. Your respiratory tract and your gut are actually external surfaces that you have internalised within the body, right? So access to these is easy. And for most of the infections that occur in these areas, reinfections happen quite frequently. We just don’t know it most of the time because these infections tend to be asymptomatic.

We are not protected against infection. We are protected against disease. One of the things that we don’t understand is how much do reinfected people spread infection? You may be okay for not being reinfected for a few months, but that’s the most that you can say.

Sandip Roy
This question that we have of all these studies about whether the virus is airborne or not or spread by droplets, where is the science on it there? Are we in for endless sanitising or masks? Because one is implying, sort of, spread by infection by surface contact, and one is implying airborne.

Dr Gagandeep Kang
The virus is airborne and the idea of airborne transmission, I think there was a lot of confusion early on between droplets and aerosols. This is just a question of the size of the particles that circulate in the air. If they are big and heavy, they will fall down. If they are small and light, they will float around for a while.

So if we look at what people should be doing, essentially it can be divided into four things. One is source control and source control means that anybody who is potentially infectious should be reducing the amount that they are releasing into the air. So what does this mean in practical terms? It means wear a mask so that you don’t infect others in case you are infectious.

The second thing is ventilation or filtration. But one of the best things that you can do is make sure that air circulation is as good as possible because the amount of viruses being light will float away quite easily. You’re diluting the air around you.

The next is distance and personal protective equipment. So that is essentially, if I stay far away from someone, they are not going to be able to get their large droplets close enough to me to infect me. And if I’m wearing a mask, then I’m protected from the droplets that are floating around.

The third is what you refer to, which is the hand washing and the sanitisers and the hygiene. There has actually been studies that show that the highest viral loads are found on a flat surface. So on the floor. On tabletops, so if you are sanitising those are the surfaces that you should be focusing on.

Sandip Roy
One other quick question I had is in terms of these tests, these rapid tests people are doing. I mean, here in Calcutta where I am, you can actually quite easily go to a primary health care centre and get a nasal swab test done. But then you hear so much about them being false positive and false negative. A) Are they reliable? And B) Why is there such a high rate of false positives and negatives there?

Dr Gagandeep Kang
So with most of the rapid antigen tests that are being used by the government facilities, the problem from the data that I’ve seen is not a question of false positives, but a problem of false negatives. And to understand that, you have to understand how the regular test, the RT-PCR is done, versus the Rapid Antigen test. In the RT-PCR, what you’re doing is you’re breaking open the virus, you’re accessing its nucleic acid, which is RNA, and you’re converting that RNA to DNA and multiplying it many, many, many times. And then you’re looking to see, is this DNA there? And if you find it and you find a certain amount of it, it tells you how much virus was there. So this is called amplification, right? So if there was a lot of virus to start with, you will find it faster. If there was very little virus to start with, then you need to multiply it many more times before you find it. So it takes longer.

Then if you look at the Rapid Antigen test, what that is doing is not looking at the nucleic acid, it’s looking at the protein shell of the virus. Now, if you look at the protein shell, then that depends on how much protein is there. You can’t multiply protein without the virus infecting host cells. So if there is lots of virus there, there’ll be lots of protein and the Rapid Antigen test will find it. If there is very little virus there, there’s a good chance that the test will not be able to find that very little amount of protein and the test will then be a false negative.

Sandip Roy
So these reports that India has passed its peak in September, we read this report and we felt hopeful about that. But given that Diwali is coming up and looking at what is happening in Paris and Germany and the US right now, are you confident that we’ve actually passed the peak or is there a big second wave coming?

Dr Gagandeep Kang
All epidemics have cases that go up as the virus spreads and then when spread reaches an equilibrium because infectious people are now not encountering more susceptible people, then you will start to trend downwards. Now, will there be another peak? Is this a wave? Is this a second peak? Really depends on behaviour. We know how control is to be affected. Control is affected by not allowing the virus to spread from person to person. If spread happens, it’s because infectious people came in contact with susceptible people. So our behaviours will determine what happens.

Sandip Roy
Well, Emmanuel Macron said the virus is circulating at a speed that not even the most pessimistic forecasts had anticipated. Do you think that a second shutdown would be, or I don’t think it would be second, but a shutdown would be necessary again in India, as is happening in Europe?

Dr Gagandeep Kang
I think it’s all a question of can people behave well or not. So it’s not a question of lockdown, or no lockdown, it’s a question of what are the behaviours that we can inculcate in our population and our compliance with those. Our responsibility is communication, education and monitoring, supported by all the public health activities that we already know needed. Testing, tracing, and isolation are the basis of prevention of transmission, and our hospitals need to be ready to handle people who develop severe disease.

Sandip Roy
Finally Dr Kang, I’ve heard that after looking at this for a while, people have said that in many ways the virus is behaving quite predictably. So in that case, what is still the most unpredictable thing about the virus? For me, as an outsider with no medical training, it seems to be about who will actually develop a severe disease as a result of infection and who won’t.

Dr Gagandeep Kang
Exactly the same as you. We have no understanding of what predisposes one person and not another for severe disease. If we could understand that, we would have a much better way of thinking about what we could do to protect against severe disease. We need to understand that this virus, in terms of infection is predictable, but in terms of disease and the consequences of infection, this is something we don’t understand now. Both who will develop the most severe disease and who will have long term outcomes from this, the so-called long covid syndrome that is being described, we have no way of predicting right now who will go in which direction.

Sandip Roy
Well, we’ll have to leave it there. Thank you so much for taking the time today.

Dr Gagandeep Kang
Thank you, Sandip.


You can follow us and leave us feedback on Facebook and Twitter @expresspodcasts, or send us an email at podcasts@indianexpress.com. If you like this show, please subscribe and leave us a review wherever you get your podcasts, so other people can find us. You can also find us on https://indianexpress.com/audio.

More info
More less
Why life won’t go back to normal even after a COVID-19 vaccine, with Dr Gagandeep KangAs the COVID-19 pandemic continues to rage on, a lot of people remain hopeful for a vaccine. And right now several vaccines are in the works. But how will we know which is the right one? How effective will it be? Will there be enough for all of us? And will we be able to stop social distancing then? To answer these questions and more, Sandip speaks to Dr Gagandeep Kang, microbiologist and professor at the Christian Medical College in Vellore. Dr Kang is credited with pioneering work on an indigenous Rotavirus vaccine, and is the the first Indian scientist to be elected fellow of The Royal Society. Transcript: Sandip Roy Recently we heard that India has crossed its COVID peak in September. But then this week the global tally of COVID-19 cases jumped up by more than 500,000. That's a one day increase record since the beginning of the pandemic, and Europe is preparing to go for a shutdown again. But there are vaccines in the works. Several. I don't know about you but the more options I get, the more confused I become. How do we know which is the right vaccine? Will we have enough? If there's a 50% efficacy rate then how confident can I be that I'm protected, even if I have the vaccine? And when can I take off my mask and hug a friend again? So this week we reached out to Dr Gagandeep Kang, microbiologist and professor at the Christian Medical College in Vellore, who is credited with pioneering work on an indigenous Rotavirus vaccine. And is the first Indian scientist to be elected fellow of The Royal Society. Dr Gagandeep Kang, welcome back to the show. Dr Gagandeep Kang Thank you, Sandip. I'm happy to be here. Sandip Roy Well, vaccines are on everyone's mind these days. So where are we now? Dr Gagandeep Kang Well, we have 321 vaccine projects ongoing around the world. We have over 40 vaccines that are being tested in humans and over a dozen that are in phase three efficacy trials. Sandip Roy If you were a betting woman, are you more optimistic about one of the other? Dr Gagandeep Kang I'm not more optimistic about one particular candidate over any others. I think the readouts that we've had so far from the phase one and phase two studies are showing us that all of the vaccines that have been evaluated are safe and immunogenic. But safe and immunogenic does not necessarily mean effective in preventing disease and that's the outcome that we will get from the Phase three trials. Given that we have a dozen plus candidates that are in phase three. I think it's very likely that we will have several successful candidates. The question will be, when will we know this and how effective will they be. Sandip Roy Does this mean that the different vaccines would produce different levels of immunity? Dr Gagandeep Kang That's correct. So if we look at immunogenicity, the vaccines that we've had in the market so far, all the routine vaccines that we take, usually we look to see whether they are producing antibodies, which comes from the adaptive immune system. When you get infected or you get vaccinated, the body recognises that as foreign and produces antibodies against it. So that is an arm of the adaptive immune system that's called Humoral immunity. In this case and with a few other vaccines that have been tried before, we also look at another arm of the immune response, which is called Cell-mediated immunity. And in Cell-mediated immunity, you see what is the quality of the immune response, do you generate memory, and also whether there is a chance whether this vaccine might go down the wrong way, creating a response that might be harmful at some point in the future. So with all of the vaccines that are being developed, both arms of adaptive immunity, the Humoral arm and the Cell-mediated are being evaluated. Sandip Roy So I've been reading things where it says the vaccine, like Covaxin, is apparently about 60 percent efficient. But what people think Oxford is also similar, but above what level of or what level of efficacy would we need in a vaccine to eliminate the need for social distancing and masks? Dr Gagandeep Kang You'd need a perfect vaccine and you would need to vaccinate everybody in the world. So when you say that Covaxin and the University of Oxford vaccine are 60 percent efficacious, actually, they're not. We don't have that information. What we do have information on so far is only on the immune responses that have been generated in the phase two trials. And we are waiting for the results of the phase three. The way the trials are set up, the University of Oxford and Bharat Biotech cannot tell you that the vaccine is 60 percent efficacious because they are blinded. They don't know who has received the vaccine, who has received the comparator, or the placebo. Sandip Roy So from a public health perspective, when the WHO says a COVID-19 vaccine should be at least 50 percent effective to be approved, do you think that benchmark is good enough or is actually low? Dr Gagandeep Kang There is practically no vaccine that is 100 percent efficacious. Some of the best vaccines we have, like measles, are 90 percent plus. The malaria vaccine that has only about 30 percent efficacy. So while we would all like a perfect vaccine, sometimes we have to work with vaccines that are less than perfect. And the 50 percent efficacy is actually not too bad for a respiratory virus. Most of the influenza vaccines that we use vary from year to year from not working at all to having 60- 65 percent efficacy against certain strains. What WHO has set as a benchmark and the FDA has done exactly the same as well, is to say that we need a 50 percent point estimate of efficacy. Which means that in the trial, it must be 50 percent. But around that 50 percent, which is the result from the trial setting, is an understanding that when we use the vaccine in other populations, larger groups, we may not find exactly the same result. So 50 percent is the middle of a range. And that range for both FDA and WHO is a minimum level of 30 percent protection. So though we will get an estimate of 50 percent in the trial, actually, the true efficacy of the vaccine may be anywhere from 30 percent to 70 percent. Sandip Roy So in that case, to go back to the original question, if it's true impact is about 30 percent, we will still be needing to practice social distancing and masks and all of those things we are doing now? Dr Gagandeep Kang Absolutely, because until we have something that can act as a readout to know whether a person is protected or not. This is called a correlate of protection. It may be an antibody level. We won't know for sure among all the people who have received vaccine, which ones are protected and which ones are not. So life is not going to go back to normal the minute we have a vaccine. We will continue to need to be careful the same way that we are doing now. Sandip Roy Damn, just ruined... Dr Gagandeep Kang I'm sorry, I'm not bringing good news for you but this is real life and, you know, public health. But the vaccine will be a game changer because what will happen is that infection will slow down, will stop spreading so quickly because the bulk of people will then be protected. So we will see less severe disease in hospitals and we will reach a stage where our testing and tracing will allow us to handle the disease much, much better. So if we look at Taiwan, for example, right now, because they have outstanding testing and tracing, they've gone two hundred days without having a case. All the cases currently are imported. Sandip Roy So the other thing I keep reading about, and I would love to have you explain it in lay terms, is this thing about the virus's basic reproduction number and what it represents. Do we know this number for COVID? And what does it mean in terms of vaccine development? Dr Gagandeep Kang So we have a sense of this number and it's somewhere between 2 and 3. Sandip Roy One case can infect two to three people? Dr Gagandeep Kang Exactly. So if you have a completely susceptible population, nobody's ever been infected before, then each person who gets an infection is estimated to spread it to two or three other people. The problem is that this assumes that everybody uniformly comes in contact with three people, and those three people, among all those that you come in contact with, will be uniformly susceptible to getting infected and developing disease. We know that that is not the case. There is variation in all humans, in all societies. And as long as this 2 to 3 is maintained, as long as there is anything above 1, that means that the overall number of people acquiring infections will continue to grow. If you can bring it down below 1, then that is a disease that will die out in that population, as has been shown in Taiwan. So with everything that we do, social distancing, masking, we are already modifying R (Reproduction). But a vaccine will help us do that even better. It's been estimated that masks themselves reduce infections by somewhere between 20 and 40 percent. Now, if you had a vaccine that is 50 percent efficacious, you're pretty much getting into the range of getting your R below 1. Sandip Roy Since you brought up masks, here's one burning question people had. Initially, people said, 'Oh masks, if you wash them, then they become useless'. Then I keep seeing ads for reusable masks. People say you can use a mask 30 times at least. What's the deal with safe practice when it comes to masks? Dr Gagandeep Kang So the best masks are the ones that stop the least particles going out and coming in, and these have numbers attached to them. 99, 95, 90, etc. And then you have the regular surgical masks, the blue and green ones that have multiple layers and can have your loops or ties. And then you have the various reusable cloth masks. Now, if you look at an order, the best masks are the rated masks, and those can be reused with stabilisation in between. And usually this is done in a facility that can do the sterilization. You can use ethylene oxide gas. Some people use ultraviolet radiation, but those masks are supposed to be disposable, but can be used, reused a few times. If you look at the surgical masks, those should be disposed off, they should not be reused and they should be disposed of as infectious waste. Now, if you look at cloth masks, reusable masks, those can definitely be reused. The most important thing about masks is to make sure that when you wash and dry them, they are really dry. If you put them out in the sun so much better because you're getting temperature, UV-rays and drying all at the same time, which makes sure that you are removing any infectious material from the masks. In terms of efficacy, obviously, cloth and reusable masks are the least effective, but even they used appropriately do stop a large proportion of the large droplets that can transmit the virus. They are less effective against the smaller droplets or aerosols, but still reduce the numbers that are either put out or can come in. So whatever you do, this using masks is a good idea. Reusing masks, for the N 95s, and N 99s, that requires professional sterilizations. Surgical masks, not to be reused. Cloth masks and bought reusable masks can be reused, but make sure that after every use, clean them and make sure they are absolutely dry before you reuse them. Just because it's a reusable mask, don't use it for three days and then wash. [Ad Break] Sandip Roy Now to go back to the vaccine. So the government has said that 25 crore people will be inoculated by July 2021. From a public health perspective, is it wise to give out a date like that in advance of, you know, before there's actually even a vaccine out there? Dr Gagandeep Kang I think the reason that the government has done that is to provoke planning. And make sure that they have internal deadlines for themselves to be ready. Remember, this is going to be something we have never done before. We've never had campaigns to immunise adults across the country before. We've never had a campaign that not only did not target all adults, but targeted only the elderly. We've never had a campaign that targets by occupation. Will it work by June 2021? I don't know. I don't know if we'll have five hundred million doses available to India to immunise two hundred and fifty million people by June of 2021. The global estimate that's come from CEPI is that the entire globe will have between two and four billion doses by the end of 2021 across a range of platforms. India having five hundred million is predicated on an Indian product being successful and having that level of manufacturing capacity as well as getting supply from other parts of the world. So there's a lot of ifs and buts in there, but it demonstrates that there is a commitment to deliver. Sandip Roy But is there going to be a need to actually inoculate twenty five crore people, or is the way vaccines work is you, sort of, build a ring of fire around the most vulnerable, for example, health care workers? Dr Gagandeep Kang So it depends on what the goals of your vaccination program are. If the goal is to prevent severe disease and mortality, then the first thing that you do is to try and protect those who are most susceptible. And that would be really the elderly and those with comorbidities. That's not a ring of fire strategy, that's actually treating those people directly. Preventing disease in them. But we don't know yet whether all of the vaccines that we are making, are going to protect the elderly, are going to protect those with comorbidities. We need those studies to be done. So if we have priority populations, then one is preventing disease and then preventing infection in those who are most at rise. Which is what you highlighted, health care workers, because they are constantly exposed to the virus. But also there is a responsibility of reciprocity. These are people who are putting themselves at risk to look after potential patients and therefore they need to be protected. This also applies to other health frontline workers. So it does require a strategy because there isn't going to be enough vaccine for everybody. Sandip Roy But even among health care workers, we are going to have to make priority choices, right? I mean, should a ward boy in a hospital have prioritised access to a vaccine before, say, a specialist surgeon? Dr Gagandeep Kang I think we should stratify on the basis of risk. So definitely I would prioritise the word boy over, let's say, a clerk who sits in the office of a surgical unit. But the surgeon is also at risk because he's operating on potentially infected patients. Sandip Roy And now this idea that everybody's been talking about, herd immunity. It's something we've all learned recently. Your profession knows about this for a long time. How realistic is this idea of herd immunity? Dr Gagandeep Kang I think herd immunity is a well-known phenomenon for infectious diseases, but a lot depends on how infectious that agent is and it depends on the duration for which an infected person is protected against reinfection. So if we take measles as an example, measles is the very, very, very infectious disease, which means that you need for the bulk of the population to be protected against measles, for herd immunity to be achieved. For measles to stop spreading within that community. It's been estimated that for measles, we need 95 percent of the population to be either infected or vaccinated in order to achieve herd immunity. And that happened in places like the US, the UK. But as soon as vaccination rates dropped, then we saw a resurgence of measles in those countries. If we look at other diseases that are not as infectious, you can achieve herd immunity at lower levels of exposure in the population. So, for example, the idea of smallpox. You had mentioned that you have this ring of fire. Ring vaccination was actually used to contain smallpox by making sure that people who came in contact with infected individuals were vaccinated and did not spread disease further. So it didn't require for as much of the population to be exposed, infected or vaccinated to stop transmission of smallpox The second point I brought up was the duration of protection. For common cold viruses, the adenoviruses, the coronaviruses that cause common colds, the duration of protection can last for months or a few years. Which means that if you are relying on a vaccine to protect, then you might need to give the vaccine very frequently to maintain the levels of immunity that are required in the herd for protection. We'll just have to wait and see how long protection from vaccination or infection lasts in the case of Sars-COV-2. Sandip Roy Well, that's an area of some confusion. I was just reading in Science magazine that you retain antibodies for at least 5 months. But then I read this other study in L.A. which found that people with mild cases of covid-19, their antibodies against it dropped sharply over the first 3 months after the infection, and it decreased by roughly half every 36 days. So at that rate, the antibodies would disappear within 6 months or a year, wouldn't it? Dr Gagandeep Kang Well, this is confusion confounded, isn't it? Sandip Roy Yes, it is! Dr Gagandeep Kang And the reason for that is that every study that we've seen so far measures different things. So in the early stages of an epidemic, everybody is trying to get all the information that they possibly can. And if we look at antibody responses, the virus has many different proteins. And when a virus infects human beings, we will make antibodies against all of the viral proteins. Some of them matter. Some of them are just signatures that the virus was there. So these will last for different periods of time. And the tests that we develop to measure these antibodies can also vary. So are we really measuring in every study the most important proteins for protection from infection? We don't know. Additionally, these are only antibodies. There are also the cellular immune responses, the T cells, which are important in determining protection from infection. And there are studies that show even if you have a mild or asymptomatic infection, you do make responses that are cell based and those can potentially either give you protection or modify the severity of disease if you get infected. Sandip Roy So in that case, the cell sort of retains a memory of the disease and how to fight it. But if I have a mild infection or I'm asymptomatic, does that mean I will have fewer antibodies and that a few months from now the chances are I will have no antibodies? Dr Gagandeep Kang It's possible that you may have no measurable antibodies after a few months, that still doesn't mean that you are not protected because then we should be looking at what kinds of T cells you have and whether they recognise the virus or not. So your highest level of antibodies is after you've just seen the infection and it comes down after a while. But having once been exposed to an infection, the second time your response is much quicker. And that's because you are retaining memory and the cells, the memory cells, will kick off much faster when they see the virus the second time. Sandip Roy So someone who's had COVID and recovered, or maybe they had a mild case and they're fine now, what should they be doing? Because there is also a sense of complacency where people feel like, 'OK, I've got it, I'm done with it'. Dr Gagandeep Kang It's important to remember that this is a mucosal infection. Your respiratory tract and your gut are actually external surfaces that you have internalised within the body, right? So access to these is easy. And for most of the infections that occur in these areas, reinfections happen quite frequently. We just don't know it most of the time because these infections tend to be asymptomatic. We are not protected against infection. We are protected against disease. One of the things that we don't understand is how much do reinfected people spread infection? You may be okay for not being reinfected for a few months, but that's the most that you can say. Sandip Roy This question that we have of all these studies about whether the virus is airborne or not or spread by droplets, where is the science on it there? Are we in for endless sanitising or masks? Because one is implying, sort of, spread by infection by surface contact, and one is implying airborne. Dr Gagandeep Kang The virus is airborne and the idea of airborne transmission, I think there was a lot of confusion early on between droplets and aerosols. This is just a question of the size of the particles that circulate in the air. If they are big and heavy, they will fall down. If they are small and light, they will float around for a while. So if we look at what people should be doing, essentially it can be divided into four things. One is source control and source control means that anybody who is potentially infectious should be reducing the amount that they are releasing into the air. So what does this mean in practical terms? It means wear a mask so that you don't infect others in case you are infectious. The second thing is ventilation or filtration. But one of the best things that you can do is make sure that air circulation is as good as possible because the amount of viruses being light will float away quite easily. You're diluting the air around you. The next is distance and personal protective equipment. So that is essentially, if I stay far away from someone, they are not going to be able to get their large droplets close enough to me to infect me. And if I'm wearing a mask, then I'm protected from the droplets that are floating around. The third is what you refer to, which is the hand washing and the sanitisers and the hygiene. There has actually been studies that show that the highest viral loads are found on a flat surface. So on the floor. On tabletops, so if you are sanitising those are the surfaces that you should be focusing on. Sandip Roy One other quick question I had is in terms of these tests, these rapid tests people are doing. I mean, here in Calcutta where I am, you can actually quite easily go to a primary health care centre and get a nasal swab test done. But then you hear so much about them being false positive and false negative. A) Are they reliable? And B) Why is there such a high rate of false positives and negatives there? Dr Gagandeep Kang So with most of the rapid antigen tests that are being used by the government facilities, the problem from the data that I've seen is not a question of false positives, but a problem of false negatives. And to understand that, you have to understand how the regular test, the RT-PCR is done, versus the Rapid Antigen test. In the RT-PCR, what you're doing is you're breaking open the virus, you're accessing its nucleic acid, which is RNA, and you're converting that RNA to DNA and multiplying it many, many, many times. And then you're looking to see, is this DNA there? And if you find it and you find a certain amount of it, it tells you how much virus was there. So this is called amplification, right? So if there was a lot of virus to start with, you will find it faster. If there was very little virus to start with, then you need to multiply it many more times before you find it. So it takes longer. Then if you look at the Rapid Antigen test, what that is doing is not looking at the nucleic acid, it's looking at the protein shell of the virus. Now, if you look at the protein shell, then that depends on how much protein is there. You can't multiply protein without the virus infecting host cells. So if there is lots of virus there, there'll be lots of protein and the Rapid Antigen test will find it. If there is very little virus there, there's a good chance that the test will not be able to find that very little amount of protein and the test will then be a false negative. Sandip Roy So these reports that India has passed its peak in September, we read this report and we felt hopeful about that. But given that Diwali is coming up and looking at what is happening in Paris and Germany and the US right now, are you confident that we've actually passed the peak or is there a big second wave coming? Dr Gagandeep Kang All epidemics have cases that go up as the virus spreads and then when spread reaches an equilibrium because infectious people are now not encountering more susceptible people, then you will start to trend downwards. Now, will there be another peak? Is this a wave? Is this a second peak? Really depends on behaviour. We know how control is to be affected. Control is affected by not allowing the virus to spread from person to person. If spread happens, it's because infectious people came in contact with susceptible people. So our behaviours will determine what happens. Sandip Roy Well, Emmanuel Macron said the virus is circulating at a speed that not even the most pessimistic forecasts had anticipated. Do you think that a second shutdown would be, or I don't think it would be second, but a shutdown would be necessary again in India, as is happening in Europe? Dr Gagandeep Kang I think it's all a question of can people behave well or not. So it's not a question of lockdown, or no lockdown, it's a question of what are the behaviours that we can inculcate in our population and our compliance with those. Our responsibility is communication, education and monitoring, supported by all the public health activities that we already know needed. Testing, tracing, and isolation are the basis of prevention of transmission, and our hospitals need to be ready to handle people who develop severe disease. Sandip Roy Finally Dr Kang, I've heard that after looking at this for a while, people have said that in many ways the virus is behaving quite predictably. So in that case, what is still the most unpredictable thing about the virus? For me, as an outsider with no medical training, it seems to be about who will actually develop a severe disease as a result of infection and who won't. Dr Gagandeep Kang Exactly the same as you. We have no understanding of what predisposes one person and not another for severe disease. If we could understand that, we would have a much better way of thinking about what we could do to protect against severe disease. We need to understand that this virus, in terms of infection is predictable, but in terms of disease and the consequences of infection, this is something we don't understand now. Both who will develop the most severe disease and who will have long term outcomes from this, the so-called long covid syndrome that is being described, we have no way of predicting right now who will go in which direction. Sandip Roy Well, we'll have to leave it there. Thank you so much for taking the time today. Dr Gagandeep Kang Thank you, Sandip. You can follow us and leave us feedback on Facebook and Twitter @expresspodcasts, or send us an email at podcasts@indianexpress.com. If you like this show, please subscribe and leave us a review wherever you get your podcasts, so other people can find us. You can also find us on https://www.indianexpress.com/audio.
share