 Hello and welcome to NewsClick. Today, we are going to discuss at least some positive results that seem to have come from the recovery trials in Oxford. Now, we have with us Satyith Rat, who has been educating us about the various medical and the health aspects of this particular epidemic, COVID-19. Satyith, for the first time, we have some positive news which says trials have succeeded, at least it's only a press release, but the trials have succeeded in showing a significant drop in deaths using dexamethasone, the esteroid, which is quite easily and cheaply available. Yeah, so this is one of those examples, I think, where it's what slang would let you call a no brainer. In fact, the Oxford University Press release itself points out that dexamethasone, which is simply one of a large variety of corticosteroids that are clinically in wide use for many decades, and all of those uses, one way or another, broadly, reduce inflammation. Okay. If you look at the last three months, they've been easily approaching 100 publications that have examined, thought about, tried out various corticosteroids, such as dexamethasone, in patients of COVID-19. And some have said, yes, they see an effect. Some have said, no, they don't really see an effect. Pretty much all of them say, we at least haven't seen any bad effects. So there's no problem with trying it out, exactly how to use it, at home to use it, it still remains the same. So the real novelty of the news from Oxford, and I hasten to point out that it's news, we have yet to see any data leave alone a peer reviewed publication. So this is not even at the pre-print level. This is at the level of a press release alone. Like the Gilead science result on Remdesivir. So, and then as we pointed out at that time, it's not surprising given the anxiety around that these releases are happening. But at least the Oxford release cannot be looked at suspiciously with the perspective of, are they trying to increase their share value and so on and so forth. Because dexamethasone is just a generically available drug. It's very cheap. Even in India, I think you can get it for 20 is very, very cheap in few years, virtually. Absolutely. So, and if the claim is correct, and I see no reason to think that it's not, then these are reliable statistically robust results that say that a cheap generic easily made easily accessible already very widely available and accessible because it's used in such a great diversity of situations and circumstances. Drug can provide an advantage in the most seriously ill COVID-19 patients. So, this is the other part. This is really for those who are seriously ill, which means, as we have discussed earlier, there is a serious lung inflammation and therefore taking care of that and dressing that would at least help in reducing the number of deaths. That's the basic underlying issue with using this kind of corticosteroid for COVID-19 serious cases, right? Yes. There's an interesting little wrinkle into that, which the press release, which is really the only documentation we have available to us, points out quite helpfully that the improvement seems to be most striking in the most seriously ill patients. Those are ventilators. It's a little less striking in those who are not quite as ill, meaning those who are on oxygen, but not on ventilators. And it's not apparent so far at least in those who are only moderately ill. And an interesting issue related to that is the likelihood that both inflammation in the lungs and overflow inflammation all over the body, what physicians would refer to as systemic inflammation, which simply means body-wide inflammation, which you begin to see in seriously ill patients of COVID-19. That's the situation in which an anti-inflammatory steroid like dexamethasone seems to help most. So this is really not a magic bullet that it sort of solves the problem of COVID-19. It's if you're really seriously ill and again this is your body reacting to the COVID-19 infection, in which case of course what you are saying is this are the kind of things symptoms you would see and these are the kind of patients in which it has the most effect. But again, the most we are talking about is relatively say 15% to 17% improvement in the mortality rate, which is significant. We have nothing otherwise as of now not really too much, but that's the kind of figures we're talking about. It's not that all the, it's a 1 in 8, not that all the 8 get cured. So that is also the other part. Absolutely. And let me underline this. This is not a new drug, but it's not simply not a new drug. This modality of treatment is not a new discovery. Yes. In fact, I'm told that a lot of the hospitals are already using corticosteroids for this kind. Stonish me if everybody was not already using corticosteroids in at least some patients severely in with COVID-19. Not simply that, for the past decades, there has been an ongoing investigation, debate and exploration about the role of corticosteroids in a whole range of both viral and bacterial infections that lead to body-wide inflammation. The body-wide inflammation being called septic shock. Okay. That's what is called septic shock. Okay. And in a certain sense, the most severely ill patients of COVID-19, remember that we have referred to their situation as being caused by something called a cytokine storm, is essentially a kind of septic shock. And for our hearers, people who are watching us, cytokine storm is the one which really was the major killer in the influenza epidemic of 1980. And this is the one of the key killers also in this particular case. Storms are in fact, as I said, what kill severely ill patients in a whole range of bacterial infections. So the use of corticosteroids has always been attempted, tried, debated, worried over. So the worried over part is interesting. And it's interesting because the Oxford press release actually provides an entry point for that. Note that what the Oxford press release points out is that they are using the low dose regimen of dexamethasone for 10 days. Okay. And the significance of this is to do with the fact that dexamethasone, like all other corticosteroids, tends to reduce inflammation. But inflammation is the body's and the immune system's way of containing infection. So you really want to control inflammation completely. And as a matter of fact, in a variety of local applications of dexamethasone in the eye, in the nose, and so on and so forth, a major worry quite frequently is that prolonged high-dose use will lead to unconscious infections in that location because you are shut down in inflammation. So effectively you are controlling the immune storm, so to say, but you don't want to take away the immune response altogether because if you do, then of course infection persists. So this is why the low dose regimen is an interesting wrinkly in the story. And again, it's not new. There is extensive literature that low dose dexamethasone or its relative regimens in situations of severely ill patients with infections does not suppress anti-infective properties, whether or not it suppresses inflammation enough to give clinical utility or not. So this is really one of those trials where and it's sort of expected but carefully metered intervention has been tried in the public good, in what seems to be a very well-done trial and has resulted in a reasonably reliable outcome that can be applied at least in one section of patients severely ill with COVID-19. So that's an interesting issue also because what you said was one of the arguments given initially, not later. Steroids may not be good because that may in fact reduce our immune response to the virus and that may in fact help the virus to take control of the patients, so to say. So later on it was said, don't know that's not such a big issue and so on, but that was initially one of the arguments about steroids. Oh absolutely, yes, which is why I'm pointing out that the regimen that is being used is actually a regimen that independent of COVID-19 has been tried in other infections and inflammations and has been sort of shown not to affect anti-infective bodily responses too much and therefore has been argued to be sort of oh this is safe enough that if you try this and if it helps inflammation it'll be really useful. Now two other medicines, one is remdesivir which we have talked about experimental medicine virtually because trials are still as you said some no scientific results have come in the sense of a paper or even a pre-print it's only again a press release but remdesivir is expensive even in Bangladesh which is now producing it, it's $65 a dose and that's what I'm told is the price. And we are forbidden to import it from Bangladesh. We are forbidden to import it from Bangladesh and we are not producing it here either nor has a falsary licensing procedure started. So that's good. We are not producing it because apparently before companies that are ready, willing and able to produce it, I'm not being given the necessary approval paperwork to produce it. Companies are ready but the government has not given them permission. In the public sphere. And again the question of course there is there is the sort of under compulsory license. Gilead has actually allowed them, is it a collaboration? Okay so that is one but again it's if it's a Bangladesh price it's still going to be expensive unlike Dexamethazone it's really very cheap. The third again which is also an anti-inflammatory Tocillizumab if I'm pronouncing it correctly that's that's also being tried and it seems to have given some good results. Which one? Tocillizumab. Tocillizumab. So one of those maps. So in the first place let's get something clear. We're talking about two separate categories of medications. One category is medication that actually interferes with the life cycle of the virus. The second medication that doesn't do anything to the life cycle of the virus that affects like we said about Dexamethazone inflammation in the body in response to the virus. So remdesivir or the HIV related drugs lopinavir returnavir that were being tried earlier are all medications that interfere with virus life cycle. They don't do anything to the inflammation. On the other hand both Dexamethazone and Tocillizumab interfere with inflammation. They don't do anything to the virus life cycle. So the body is left to its own devices to deal with the virus only reducing inflammation especially bodywide inflammation which is throwing off multiple organ systems into the setting. That is reduced effectively what these medications do is allow the patient to survive while their body deals with the virus. And you know Saty, the Tocillizumab is again big monoflonal antibody. Again a very expensive drug. It's an extremely expensive drug especially in comparison with Dexamethazone. It is a drug that has to be given as an injection. Dexamethazone can be taken orally. It's not an easy drug to manufacture in even undercompensating licensing should such licensing be done. So absolutely there's no question that there is a difference. However the fact of the matter is that Dexamethazone is a solution. It will bring down a very wide range of inflammatory pathways and if you use low doses then all these pathways will be reduced to a relatively lower extent. Tocillizumab on the other hand is directed against one major inflammatory pathway the interleukin six pathway. It leaves other inflammatory pathways relatively untouched and there are pros and cons of these two what I'm calling a surgical knife approach of Tocillizumab versus a sledgehammer approach of corticosteroids. There'll be trade-offs in individual patient situations. Interesting enough Tocillizumab is also being tried in the recovery trials of the Oxford University and they have not reported positively on it as yet. So there are some reports that yes it has some good results but it doesn't seem to have as significant the result appears. The caveat there is even for the Oxford trial as much as for you me and our listeners Dexamethazone is cheaper than Tocillizumab and therefore I have a very strong suspicion I might well turn out to be wrong. I have a very strong suspicion that it would not be surprising if the number of patients recruited in the Dexamethazone arm has so far been much larger than the number of patients successfully recruited in the Tocillizumab I don't think that we can very easily make these conclusions. What we can see is it's actually in thousands so that's much larger than what you would see even with remdesivir or with Tocillizumab. But exactly like Dexamethazone Tocillizumab has also been reported over the past three months to give no harmful effects and in some reports some gain in some reports not a lot of gain but none of those are this systematic clinical trial which will give reliable and over. See you've been holding for a long time the argument that remdesivir would kind of medication would help in the initial phase but once it's really taken hold of the body then it really doesn't lead to significant differences and that is what we also found that remdesivir didn't really reduce the end point which it did one of the end points which was production of deaths but this particular application Dexamethazone seems to have helped with that end point. Mean the distinction between two categories of medications one interfering with the virus life cycle one interfering with the inflammation. If you don't have a lot of inflammation then the medications that reduce inflammation are not terribly indicated even leave alone being useful. So clearly if all you have is a dry cough and a bit of fever for a few days you don't want to be taking Dexamethazone at all regardless of whether it works to reduce your cough by one day or not you really don't want to be taking Dexamethazone. On the other hand as you point out I have been saying this earlier that interfering with the virus life cycle in the late stages of body-wide inflammation driven sickness may not give a huge advantage and that's what you're going to do but let me point out that if we look at it from the point of view of an epidemic then the number of days that an infected patient remains infectious and transmits virus is of great concern from the public health point of view. Okay and from that point of view I would be very anxious to look at the reduction in the period of infectivity with antiviral drugs in mildly symptomatic individuals and if we can achieve that and if we can compulsory license an effective drug in that situation then we will not be you're perfectly right interfering with the death of a severely ill patient I admit but we might actually prevent fairly large numbers of people from dying simply because we are interfering with the transmission efficiency of the virus. Effectively less people get infected than the chances of people getting more seriously infected also reduce therefore the benefits so according to you even if it is not that effective in seriously infected patients seriously affected patients it still remains a drug which could help us in fighting the epidemic. If we try it from that public health perspective as you. Okay so good we have two at least adults in our quiver at the moment for two different purposes both having functions in the epidemic so in one case when will it be available in India other at least widely available so we seem to be in a slightly better position with respect to drugs provided of course we start manufacturing revolutions and selling it in India thank you very much. All this of course is purely at the level of news conferences this is science and technology via news conferences which has its own gains and losses. Thank you very much Satyith for being with us sharing with our listeners your views this is all the time we have the news click today do keep watching news click.