 Hello and welcome to NewsClick. Today we have with us with our COVID discussions, Dr. Satyit Rath. And we are going to discuss the AstraZeneca results that have come in, which have claimed something like 70 percent efficacy with two sets of figures, one 60 percent, one 90 percent somehow average to 70 percent. Satyit, can you tell us a little bit about why we have two figures and what is this 70 percent average we seem to have got out of that? So, this reminds me of the old story of the man in prison who claimed that he was being tortured. And his captor said, he is not being tortured, average temperature he is held at is 30 degrees Celsius. Why is he complaining? It's a different matter that at one end of his body, the temperature is 90 degrees. At the other end of his body, the temperature is minus something degrees, the average of course is 30 degrees Celsius. This is what's called the statistician's delight. If a head is in the fridge and your feet are on an oven, then you are comfortable. Exactly. So, we'll come back to that in a minute. Here is a little fairy tale that is being built around the, and I as you know insist on this, around the Oxford AstraZeneca vaccine candidate. Since again, AstraZeneca is simply providing the money. Sarah Gilbert and Rupalad their colleagues at Oxford University using public funds have spent decades establishing the adenoviral vector-based vaccine platform that's being used. But here's the fairy tale that we are being told and I'll explain why I'm calling it a fairy tale. Here's the fairy tale that we are being told. The fairy tale is that they started this clinical trial and they realized that they were getting, I think, I hope I'm getting this right, they realized that they were getting somewhat lower frequencies and more mild side effects, the immediate side effects of pain, of a little bit of fever for a day or two, not feeling well as a result of adenovirus vector-based vaccinations. So, they went back and examined and they realized that they had made a mistake in the trial and that this first dose that had been given to some X number of people was actually only half the dose that had been planned. So, rather than simply correcting it, they basically set up what amounted to two separate groups. One group got half of the planned dose as the first dose and four weeks later got a full normal, what was planned as the second dose, whereas a different group of volunteers got the full planned dose, both as the first dose and as the second dose. Now, here's the little catch. These two-digit, low three-digit case number data that we've been seeing these past few days and weeks from BioNTech Pfizer, from Moderna, from the Malia Sputnik, which is even low double digit and now from Oxford AstraZeneca, are being looked at in the Oxford AstraZeneca case in these two separately vaccinated groups, separately immunized groups. And low and behold, there is a difference in the extent of protection between these two groups and even more interestingly, low and behold, the group that got the half of the planned dose as the first dose shows 90% protection. The group that got the actual planned dose, both times, is showing 62% protection. If of course, you average across these, you get 70-something percent protection. So, a great deal of server time, ink, paper, etc., has been spent on trying to provide a mechanism for this. What I would like us to think through is the reality that these are all small numbers, that the precise differences are likely to change as numbers accumulate. It's a little bit like counting votes. We've just had elections both in the United States and in one of India's largest states and we know what things look like as numbers are counted. So here Satyajit, the quick introduction that it also seems that the one with the small initial dose and the larger final dose or the normal final dose, actually is a smaller sample because if you average from 60 to 90, the numbers will say you would get 75. So the fact that you've got a different number would show that was the smaller number. The 90% immunity is a smaller number of people and effectively it's quite possible that you aren't going to end up with maybe if you did more trials somewhere between 60 to 70. That's a possibility. Statistically that seems to be there, unless as you were saying that there is a mechanism which can explain why a small initial dose and 100% dose planned dose later, 50% dose, 100% dose later, could actually work better than 200% dose. You are an immunologist, that's your specialization. Is there anything that I've seen again, reports of some again, I presume or good well-known practitioners saying this is possible, there could be mechanism, but do you think that that's a very likely case or it's just large numbers as you were saying, once we have the bigger numbers, this will actually come down. So let me put it this way. If I were writing a grant proposal for funding, I would say, of course this is potentially significant and the mechanism must be clearly understood. The first aim of my grant proposal would be, we will confirm whether this is the case or not. On the other hand, if I was reviewing such a paper that said clearly there is a difference and therefore a biological mechanism now must be operative, I would say please acknowledge that this may simply be a coincidence. Artifact of statistics rather than a biological reason why this difference exists. The second issue and I think that's a more important one, they've also claimed that the group which got the actual vaccine and after placebo that none of them were hospitalized or seriously infected, seriously infected. So would that also mean that yes, some of them did show infections but the intensity of the infection so to say or the reaction was much less than what could be normally expected or is it also small numbers? Now we move into something that's for me even more interesting because it's both mechanistically interesting, scientifically interesting and politically interesting. It's scientifically interesting because while their numbers are small, they are not the only trial to have these small numbers of severe COVID-19 illness. In every one of the previous press releases, you will find a throw away sentence that says exactly the same thing. Now I ask us if AstraZeneca is going to average between what are effectively two independent vaccine trials? What stops me from averaging across the BioNTech, Pfizer, the Moderna and these two Oxford AstraZeneca trials add up all the severe COVID-19 cases in the placebo groups and in the actually vaccinated groups and say tell us what the extent of protection against severe disease by any vaccine is. I can already hear howls of protest from statisticians, trialists as specialists call themselves and so on and so forth and then I turn around and I make the political point once again. Why oh why did we not all enroll all of these vaccine candidates in the WHO Solidarity Vaccine Trial where we would have actually been able to do this comparison? Yes, that's something that we have discussed earlier as well. Again and again. But this is what we've also discussed earlier, capitalism, pharmaceuticals and health. This is the problem that we face. It's not a medical, it's not a public health problem, it's a social problem that we have. It's a political problem. It's a problem where we as a global society and community have allowed this myth of the open competitive marketplace to limit our response to COVID-19 because by now we would have had an answer about whether vaccination protects against severe disease or not. Which is an answer we still would have to aggregate the way you are doing across the similar tribes. Coming back to the other issue that also we had discussed this earlier. There are also the issues of infections taking place. Now the numbers of people who have been infected twice has grown and it does appear that it's quite possible that in a number of cases the COVID-19 immunity would not last too long. Whether six months, one year, three months, these are different issues, but certainly lifelong immunity no and probably short duration immunity from six months to a year is possible beyond that possibly no. Again, to be verified these are only conjectures I'm making or based on discussions we have had and whatever we are reading. So the herd immunity based on infections, the Boris Johnson Swedish hypothesis and also I think there is in the United States few doctors and epidemiologists have got together have also issued a declaration to this effect. All this doesn't seem to be scientifically now true or can be very can be held to be a possible way forward. So and absolutely right and it's interesting that you bring this up in the context of these emerging data with vaccine candidates because inevitably a major conversation that's taking place around the the success of these vaccine candidates is how much of a population would we need to vaccinate to reach vaccine-induced herd immunity and that has brought back into the conversation all these issues of natural infection based herd immunity. So let me let me point out as a as an object lesson a recent analysis based on where I am which is in Pune and and the CRO survey from very small urban crowded localities in Pune that that some of my colleagues in the city have been doing and have been analyzing these past few weeks and months that was just uploaded as appropriate. Now the two interesting things about it firstly there is the statisticians stupidity that Pune was supposed to have a zero prevalence of 50 percent and yet in the five very small micro localities surveyed the prevalence varied from 35 percent to 70 percent. So averaging is stupid without context but beyond that here's the interesting piece of correlation that's embedded in that in that paper which directly addresses the herd immunity issue in an interesting way and that is that the survey was done over a fortnight in the month or so after that fortnight what was the case number in each of these micro localities and what is the correlation between the zero prevalence in these micro localities and the subsequent case numbers in these micro localities there is clearly an inverse correlation in other words if the zero prevalence was high the number of cases was low if the zero prevalence was low the number of cases was high two lessons one even with as high a zero prevalence as 70 percent the number of cases was to use a famous term from Donald Trump's hot shot legal team the number was non-zero which means that the commonly understood notion of herd immunity that you interrupt transmission and virus spread huts I could argue plausibly that even at 70 percent zero prevalence there was still transmission in the community but number two that more rationally the more people were exposed the slower was the spread of transmission this is the kind of mundane quantitative struggle based coming to terms with an infectious disease pandemic that we need to acknowledge and deal with as a reality so that's a that's the good good point to end this discussion with that the zero prevalence studies show that a that other point which you haven't said but which I know you have made a number of times that essentially you don't look at Pune as a whole you have to look at pockets and each pocket behaves differently the transmission is not taking place in a homogeneous entity called Pune but amongst a set of people who live in different localities and different networks of contacts different you know what is called different bubbles in today's language and therefore the transmission that takes place in this area is also dissimilar apart from the fact that obviously the level of immunity that you have also slows down but doesn't stop the infection from transmissions and particularly if you have a city like Pune forget about a country like India if you have a city like Pune or a city like Delhi then pockets of herd immunity is not going to stop the transmission of the disease or even spikes which happened in Pune and is now happening in Delhi so all of this shows that we are facing a situation where we need a vaccine and that's the point I really wanted to come to that if we want normal life to resume vaccine is something we would still require that slow march towards herd immunity is not going to get us there and that's the final lesson that we seem to be hearing from all of this good news still that if all the vaccines claim that the trials severity of the disease is lessened even though people do fall sick and even if the numbers of people falling sick reduced significantly then we can say we have a successful vaccine that success is not that we will eradicate the disease but we will be in control of it so I think that's a positive note to end your discussion with any last remark on that before we close the discussion no I agree entirely we should keep in mind that what all of this is telling us is that there is a long protracted multifaceted struggle that we need to deal with vaccine successes will simply give us additional useful instruments not magic bullets and for our viewers I would like to end with this note that AstraZeneca or what Satyam called Oxford AstraZeneca vaccine has of course strong Indian implications because Saram Institute has tied up with them and they are promising to start delivering to the market by possibly January market winning of course hopefully the government and those who are really on the first line of the fighting against COVID-19 our health workers and hopefully we'll start seeing action on that count depending on how the government and the central government the state governments handle it but it does seem that the Oxford AstraZeneca can be useful for India therefore we have really more of an eye on it than the Moderna and the BioNTech Pfizer vaccine which as we know the kind of temperature requirements are not suitable Oxford vaccine is 2 to 8 degrees so this is something which is more easy to handle we still have logistical issues because you have to transport track people for the duration required and also it is injectable not in oral vaccine and therefore there are additional technical requirements that are required that are there for delivering the vaccine but hope as and yet and hopefully by January we will see more action thank you Satyam for being with us and taking us to this arduous immunology route which we need to have to discuss vaccines this is all the time we have today for news click do keep watching news click and also visit our website