 Hello and welcome to NewsClick. Today we have with us Dr. Satyajit Rat, somebody who deals in the immune system, which according to the doctors is a very, very difficult area and most discussions on the immune system start by saying it is little complicated. So we have really those complications coming up today in different ways. Satyajit will start with the first proven case where we know a reinfection is taking place, Hong Kong person who was infected earlier as again shown to be infected. This time we know it's the reinfection because it's a different genetic sequence that we are able to see. Can you tell us a little more about what this really means in terms of how we identified it and what it really means for all of us? Okay, so let's start with what we didn't know, which we have come to know with the Hong Kong case. And that is we've had a lot of anecdotes floating around saying so and so was virus positive, then they became virus negative, then when they were retested they were again virus positive. And people said, oh, is this reinfection? And the trouble with that sequence being interpreted as a reinfection is that the negative test may have been wrong because... We discussed that earlier that we don't know because we are not sure of the negative test in the middle. Well, tests always have some finite probability of being wrong. So the negative test may be wrong and if that was the case then these people may simply have a prolonged viral infection rather than a reinfection. This had not been ruled out definitively so far as I have heard before the Hong Kong case. In the Hong Kong case, both the earlier positive test virus and the later positive test virus have had their entire genetic code sequenced. And the code is sufficiently different for us to say with certainty that these are two independent infections that this individual has had in a span of a few months. And in that sense, this is a true instance of reinfection. Let's look at it in simple terms. Out of a hundred people who are infected with SARS-CoV-2, how many get symptoms less than half? So the chances of any person getting infected and developing symptoms are actually a minority. So the fact that this reinfection in this particular individual was not symptomatic is not necessarily because he had an immunity from the previous infection. Okay. So what you're saying is unless we have 50 such cases, we will not be able to conclusively say whether it is the immunity, residual immunity, or whether it's a simple statistical chance that the person did not develop the symptoms. So on behalf of my statistician friends, it is astonishing that I have those. Let me modify the usual statement. There are lies, there are damned lies and both are dealt with by statistics. Quite often created by statistics also? So absolutely. So that this person was asymptomatic is not necessarily evidence that it was asymptomatic because of pre-existing immunity. Okay. Just as the fact that this person had a reinfection is not evidence that this second virus infection was materially different from the first virus infection. None of these speculations are supported by any evidence so far. But what we could also think of that after only one person has been reinfected that we know of, there may be more, but there is not hell of a lot of more people. Otherwise, you would have got more cases. I am not so sure because remember that this reinfection was discovered accidentally simply because this person was traveling and therefore in a situation where he got sampled regardless of anything. Yeah, that's true because most people are still getting tested only when they have symptoms or they are in contact with the person who has had symptoms. So it's only a very small subset of people who get tested. So we really to test a person who has been reinfected is anyway statistically is a very small number. So an interesting issue would be if everybody who came up as virus positive began to be tested that day for antibodies, especially for IgG antibodies, then we would begin to have at least a rough idea. It's quite possible that the IgG antibodies may be because of that infection. But antibodies you have to spell out a little more. As you know, it's complicated. Well, it takes a few days for us to develop IgG antibodies. So if today I'm virus infected and also have high levels of IgG antibodies, then there is at least some reason for thinking that this may be a reinfection. So there's all sorts of correlations that I suspect the field is going to begin to look very actively for in order to provide statistical heft for the phenomenon of reinfection. But at least now we know that there is possibility of reinfection. And we are back on the vaccine issue, which we have discussed earlier that we will get some protection, maybe 100%, maybe 70%. If it lasts for six months, if it lasts for two years, it may even last for a lifetime. We don't know at this point. That's where we still are. And what this shows that it is a possibility that after some time we may get a second infection, as you've argued earlier, that vaccination may give you a stronger immune protection than an infection gives you. So again, we are back to the issue that it is really complicated, right? So let me add two issues, connecting this reinfection case with the prospects of vaccination. Number one, people are using the reinfection case to say that if reinfection like this is possible, vaccines may not work. And as you pointed out, we've discussed earlier the fact that vaccination is triggering the same immune response through somewhat different contexts and pathways than the natural infection does, or at least not necessarily through the same pathways. And therefore the magnitude of a response through an infection and the magnitude of a response through vaccination are not necessarily the same. But the second point that's being made with the reinfection case is that, oh, the virus has changed, it has mutated, and therefore there is no protection any longer. At the moment, looking at the mutations of the second virus strain in this individual, there is no evidence to think that a standard vaccine response that could be generated by any of the leading vaccine candidates would not protect equally against both the first and the second. So I don't think that the mutations or the variations in the virus sequence so far have raised any immediate and imminent red flags about the durability of utility of vaccines. And that's why I had said 22 changes in the genome sequence out of 29,000, 30,000. So therefore it's a very small change we are talking about and it doesn't appear to be or probably not, again, probably not an argument that it has changed significantly. Well, let me underline that none of those changes appear to be in regions of the virus critical for vaccine protection so far. So in that sense, this is no immediate red flag for worry. Okay, so that is one part, so at least we have settled something in spite of the complications. Which is good, especially given how many red flags for worry, there have begun to come up with respect to the prospects of vaccines. You're talking about the changes in the gene sequence, genome sequence of the virus. There have been talks about the genome sequence changing and the European variant being different from the earlier Chinese one because of various mutations that have taken place. And even some speculation that this may have led to a drop in fatalities that the infection to fatality ratios are now about 1% and earlier in Italy they were about 4% to 6%. Now, do you think it's because of any change in the virus? Of course, again, it's not simple to say it's complicated. Well, there are also other factors which that we know now what to do. We know that better A, at least the hospitals do. At that time also it had hit really the old age homes and the hospitals themselves and we just didn't know how to deal with it. So therefore the fatality was higher. And so this is not a change in the virus as much as a change in our response as a society or as a health system. So let's look at this issue a little more broadly. Everybody is saying all over the world that the fatalities are dropping. That really, really seriously ill people, their percentages in the number of COVID-19 cases is dropping. Countries like India are patting themselves on the back that their case fatality rates are low. When all that may mean is that because the pandemic started later in many of these countries, they may have begun to get fatalities only at a time at which worldwide the fatalities have been dropping. So the demographic profile is different, much younger population. I think 26 or 27 is a median age of Indian population, I guess something like 43 in it. So one issue is the demographics of course, but the demographics don't explain the shift in the same population over time. In the same population over time, there are I think two or three different issues that we must keep in mind. One is that testing has expanded over this time. So it is quite possible that the biological profile of the viral disease is the same. It's just that we didn't even detect all the mild infections earlier, which we are now detecting because we have expanded it in those countries. We have expanded testing to really people who are not sick or who are only very mildly sick. And there is some indication on that also when we look at the people who are getting infected now, the figures show the younger people are also now in larger numbers. It could be simply the artifact of more testing the younger people than earlier. That's one. We'll come back to that point, but that's certainly one clear possibility. So it may simply be that we are now actually identifying more mild cases than we were to begin with. Secondly, everybody is talking about magic remedies. Particularly the US president, but a whole lot of other people who should really know how to be responsible a little bit better are talking about magic remedies. There are people who are actually talking about magic remedies, particularly in India. In India, we have an ancient and honorable tradition of magic remedies. Exactly. Baba Ramdev being the principal proponent in terms of building up an Indian fast moving consumer goods empire on that. Exactly. But let me point to the real substantive therapeutic improvement. And that therapeutic improvement comes from not just the physicians, the physicians, the nurses and the medical care systems, which I submit includes the hospital administration, the ambulances, the entire system that deals with seriously ill patients has learned week by week the world over by talking to each other. The number of my clinical intensive medicine colleagues in India who very easily say in conversations, oh, we've been in touch with our Italian colleagues and this is what they've told us is enormous. So the broad medical community, I repeat, not simply the physicians. The entire medical care system for really ill people has learned incremental multiple ways of optimizing their therapeutic approach to COVID-19. And that has made, I think, an enormous difference. And I think that's something which is underestimated. And it is, I'm sorry to use strong language, but I think it is a matter of societal shame that we do not acknowledge this very prominent community response, inclusive response, global response to an infectious disease that has emerged from the efforts of the entire community. And I'm saying entire community because, as I said, it ranges from ambulance drivers all the way to intensive care physicians. And of course, what is neglected in all of this is the technical staff of the hospital. Exactly. Not just the physicians. Absolutely. There are a number of other nurses and technical staff and all of them have to work together in order for such benefits to be visible. And the second point you make is a much larger point that optimization that follows a scientific break is always an incremental process. And incremental optimization, absolutely. Evidence driven optimization. The collective effort and not the individual efforts which we saw long and were so more so much more visible. So I was going to add that there are no patents to be taken for any of any component of this. And yet I think that it has been a major component in the improvement of case outcomes over these past few months that we are seeing. So that's the second issue. The third issue, which let me go back to your original question about virus sequence variation and whether the virus is biologically becoming less virulent. The only example we have for some virus sequence variation that may have any functional significance. There's only one and that is this famous D614G variation. Now let's take a minute and think about what we mean when we say the diseases become milder. There are two ways. Saty, we have to define the we here. All of us. Okay. There are two ways in which we think the diseases becoming milder. Not the technical community. No, no, no, not at all. One is that the proportion of seriously ill people drops because really their numbers drop. But the alternative is that the proportion of seriously ill people drops not because their numbers drop but because the numbers of people infected more mildly increases. And these two are not the same things. Absolutely. So D614G. One is a numerator and one is a denominator in my language. Absolutely. And you can imagine that if it's a numerator issue, then the virus will have become truly biologically milder. But if it's a denominator issue, then it's more complicated. So let me give the example of D614G variation as an example of how it's more complicated. So D614G apparently improves the ability of the virus to stick to cells and therefore to get into cells and therefore to spread. If that is the case, then what the D614G variant might be doing is actually infecting people who were not easily infected by the earlier variation. Rather than having become truly milder in the numerator sense, it may have become more inclusive in the denominator sense. The ratio would remain constant or be changed but for very different reasons. So there are all sorts of interesting possibilities. Clearly D614G appears to be as susceptible to the vaccine candidates that are out there as any of the other viral strains out there. So from a vaccine point of view, none of this seems to matter so far. This is no guarantee that things will not change in the future, but so far this seems to be the case. Okay Satyajit, last question and I know this is going to be a tricky one. We have talked about vaccine nationalism. One part of the vaccine nationalism is August 15th, we should have a vaccine. The famous case of the ICMR DG who wrote this famous or not so famous letter. Then we have the vaccine nationalism or for instance Trump warped speed. We will have the vaccine by fall and we will have it for the American people more connected to shall we say the fall elections. Not we will have it for the American people but we will have it for the American elections. And then of course we have the Putin case which has been really pilloried from one end of the world to the other. I suspect a little more harshly than it really deserved because people read it as if there are not going to be these stage three trials. But what when you look at the fine print, it says stage three trials will be there. But one of the problems was they had said also we will give it to those who are vulnerable. And the vulnerable included people like me who are old and therefore more susceptible to perhaps infection. So while all of this is true, but we have now also something quite disturbing because the FDA seems to be under pressure to sanction the vaccine. And this we are hearing from various leaks coming from technical community saying that the Trump administration has actually said this. That we are going to get a vaccine in September and that is going to be sanctioned by the FDA for what is it called emergency use. Now does it show and certainly by September we are not likely have completed the phase two phase three trials of Moderna. And also then the two major seems to be the front runners at least in the American scheme of things. So how do you read all of this? So in the first place, absolutely, we have just thumping machismo riddled vaccine nationalism popping up everywhere across the world. It's popped up in Russia, it's popped up in India, it's popped up of course in the United States, it's popped up in China. You name it and you will find an example under every stone and this is distressing. But it is not distressing simply because it is false and it is machismo riddled. It is distressing because it is an outcome of an underlying structural problem of major dimensions, which is that all of these vaccines are going to be sold through profit making private sector manufacturers. And therefore the unstated part of this vaccine nationalism is that countries rather than working cooperatively to provide global access to functional vaccines are placing competitive advance orders using financial cloud to reserve large blocks of putative vaccines. To the point that the US has reserved three times the number of vaccine doses as their population and connected to these both what I'm calling the machismo riddled just thumping vaccine nationalism on the one hand and the corporate money-grubbing profiteering vaccine nationalism on the other hand with its xenophobic nationalist manifestations is the underlying impetus to want to win. Kudos from vaccines for utterly petty agendas to the point that you are willing to subvert regulatory processes, which is what you're pointing to as the example of what we are hearing as pressure on the US FDA to provide emergency use authorization for a relatively unproven or as yet unproven vaccine before the 3rd of November, which is the date of the US presidential election. The talk is late September. All of this thanks together in an extraordinary manifestation of xenophobic nativist hate politics on the one hand and transnational profiteering capitalism on the other hand. There is one thing that generally irrespective of what we talk about Trump and the United States, there is a residual response globally that they are still better, the Americans are still better than others. And particularly when you compare them with Russia and China, this has been the response, but the FDA has not really covered itself with glory in this phase. They bent on the issue of hydrochloroquine earlier and also on the plasma therapy for instance, which they have again given an emergency use hydrochloroquine at least they withdrew the emergency usage or ICMR still on prophylactic use is still persisting with hydrochloroquine. As a prophylactic benefit. Now, so therefore the FDA's luster is fading after we have talked about CDC being the pillar of fighting epidemics in the world in terms of science and technological capability. It failed to produce a test for more than a month and now FDA. So we don't seem to see that the American system is also weakening under Trump's assault. So there are a couple of issues that I think we should keep in mind. Firstly, that the Centers of Disease Control, the CDC is very much part of a relatively narrow component of public health in the US government. There is very little public health in the US government. If you look at the total scale of health directed effort, the CDC is and remains a laudable component of that, but it is a very narrow component has always been another component. And of course, since it has political leadership, it remains under pressure inevitably. That's one component. A second is, I don't think any of us would have put the US FDA as a particularly reliable regulatory pillar in comparison with, for example, the European authorities. So the US FDA has always been amenable to corporate pressure, shall we say politely, in part because there has always been a revolving door between the US FDA and the pharmaceutical industry. Thirdly, the sheer xenophobic nativist hate politics of the ascendant right wing of at least the electorally ascendant right wing in the United States has put much greater pressure on any public health component. Indeed, on any component of responsible government and responsible governance in the United States compared to almost anywhere else in the world as a sea change. And with all of this, it's unsurprising that we have the US FDA responding the way it has been responding. Just as you will agree, it has been unsurprising that the Indian Council of Medical Research has been doing the things that they have been doing for exactly parallel reasons. I agree that this is certainly not the disease of medicine or public health system. It's the disease of society that we are facing. And in fact, it's a much larger crisis in terms of the assault on science itself that we are facing. Thank you, Satyit, for being with us, explaining a whole variety of issues on which things to repeat. It is complicated. This is all the time we have the news click do keep watching news click and do visit our website.