BCG trials to see if it’s a shield against Covid-19 not just a shot in the dark – Prof Andreas Diacon

Stellenbosch University Professor Andreas Diacon is launching a 500-person clinical trial aimed to determine whether the BCG vaccines are indeed a shield against Covid-19. The trial involves revaccination of BCG that's been universally applied in South Africa since 1973. Numerous reports have pointed out a correlation between infection rates for countries where BCG is universally administered as being far lower than in those countries like the USA, Italy and Belgium where it was never used. There must be some degree of evidence that it might actually work to warrant the experiments. Hope springs! – Editor.We're off to Stellenbosch and Professor Andreas Diacon joins us. Nice to have you on our Inside Covid-19 program particularly because of all the controversy that is around BCG or the TB vaccination that most South Africans get as children. Could you perhaps give us some insight into when this vaccination began in the country? .___STEADY_PAYWALL___.In South Africa it began officially in the '70s though people were given it from the '40s but not in official policy approved manner, so we will probably find patients or people with a scar that are older than they should be. We know for sure that in the '70s there was a program that was rolled out countrywide..What was it supposed to do? .At the time, when it was rolled out it was believed that it would protect people significantly from tuberculosis. Now we know that it does protect young children from very severe forms of tuberculosis but it loses its effect once people are adults. There is no difference in adult type tuberculosis in people that have been vaccinated and people that haven't been..That's interesting. In South Africa the view is at the moment maybe this is going to be a shield, maybe it's going to protect us against Covid-19?.I'm not sure if that's a generally held view. It has been an interesting observation that countries that used to have earlier and active BCG vaccination policies in babies seem to be doing better now with the Covid epidemic. However that is not an observation directly made on people, it's basically statistics that are correlated with historical information about when this vaccination was given. It's good information but it really needs to be verified that this vaccine can really protect people. There might be a lot of other factors that might explain this that we are not aware of. So it's time now to really create evidence that being BCG vaccinated protects a person from this disease..You've no doubt seen Dr. Gonzalo Otazu's correlative study. For a non-scientist, when we see that it seems to make a lot of sense and I guess that's why it's got so much international coverage. What you are saying to us is just be cautious at the moment?.Also read: Full interview, transcript: Is BCG-jab Covid-19's silver bullet? – NYIT's Dr Gonzalo Otazu..Yes, I think even the authors of this study are not entirely convinced that their observations are 100% valid. It's very clear that if all the data you have is policies in one country versus another country and how disease behaves in one country and in another country, and all of us have travelled, there are a lot more differences between countries than just that. It might have to do with cultural things, it might have to do with genetics in the country it might have to do with other factors in the healthcare system, things that are impossible to control for. The data is very robust in these countries, something different is happening. We cannot conclude that the BCG vaccination is the cause of it, until we have data that we can be sure that we have control for as much of these confounding factors as we can and that we can really promise a protective effect of this vaccine..How does one go about doing that? It's a leading question because I know that's what you're trying to do right now..Yes. Ideally you would go about vaccinating people that have never had this vaccine before and you would probably then do what we call a clinical trial, whereby you vaccinate say half of the people with the real vaccine and you vaccinate the other half of the people with something that looks like the real vaccine. You don't even let the people who vaccinate know what is in these vaccines and then you follow up and you record what happens to them and you don't make any other disturbing activity around this. After the study when everything has been observed you check who has been vaccinated with a real vaccine and who hasn't been. If you can see the protection of the group that has been vaccinated that would be very robust data proving that it actually works. .The second part of the answer is that here in South Africa most people have been vaccinated when they were born. What we are doing here trying to do exactly is the same thing, with a revaccination or a booster vaccination. We are assuming that after such a long time the immune system might have become forgetful about this vaccination and we want to revaccinate everybody with the same vaccine in the same manner that the babies are vaccinated. Just to refresh the immune system's memory and hope that that protective effect if it's then there, can be shown. .Another advantage of doing this, if a booster vaccination doesn't work, now given that people probably have been vaccinated twice, one can probably give up the idea of using this to protect people. It's then just an observation that was interesting but doesn't really help in clinical practice..How long will it take to do this whole trial?.For us here in South Africa, we are at the start of the epidemic that we assume will be with us for many months perhaps years yet we have been trying to start this study as soon as possible. Our ethics committees and regulatory authorities have been wonderful in fast tracking this for us. We have been able to source the vaccines we need to start a trial and I hope that next week on Monday we can start vaccinating health care workers. We are choosing health care workers because we believe that they will probably be in contact with that virus more than other people would be. If there is protection to be shown it would be the most easily shown in health care workers that are at risk of exposure..Also read: WHO slaps down evidence that BCG protects against Covid-19.So next Monday it begins. How long does it run for?.Initially we want to vaccinate 500 people. We are still looking for additional funding to do more. It would be better if we could do more. How long does it run? Well, we will start following up or observing people with phone calls or perhaps another digital platform two weeks after vaccination and then we will contact them monthly. We are setting up the statistics in such a way that a blinded person out there is given the data in real time manner. There is an independent committee helping the blinded statistician to figure out if there is a protection materialising over time and these people will have to decide if there really is something, that we should stop this study and consider the point proven. And then we could vaccinate everyone who had had the placebo vaccine with the real vaccination, and recommend to people in charge which in our case would be the health care administrators, to offer the vaccination to every health care worker that they have in their employ. This is dreaming a bit but we have set this study up in such a manner that if there is protection we can know it as soon as we possibly can. Then we can make the information public so it can be rolled off..How easy has it been or how difficult has it been to get health care workers to enlist?.We haven't started, we haven't enrolled anybody but the interest has been great. The superintendents of the hospital have been great, giving us access so that we can advertise for it among the health care workers. It's voluntary to participate and we will have to leave it to everyone to decide for themselves. In two or three weeks we should be able to vaccinate 500 people and hopefully by that time they'll have more funds and can vaccinate another 500. .What stimulated your interest in this field?.I am personally a researcher into TB treatments and TB vaccinations. That's what I do. When this Covid-19 crisis broke we were looking at what we could do to possibly help. I'm not the only one that had the idea of using this BCG vaccination. It has been floating out there for a while but having a research team around that is currently not able, because of lockdown to do their research work in the communities, I've decided to use all these free man hours to do this study. As long as we keep to the 500 we can probably do without much additional cost because we're just using the man hours that we're paying anyway. Beyond that, there would have to be additional people recruited and additional means created, but we will cross that bridge when we get there. At the moment getting this study off the ground is just critical because if there is something in this BCG vaccination we want to know as soon as possible..Also read: Those little BCG scars, HIV and SA's VERY low Covid-19 rate – Prof Alan Whiteside.Indeed and the optimist says hopefully there is. Are there other trials around the world that you know of who are doing similar things?.Yes, we have spoken to a group in Holland that is doing similar studies. This is interesting because the Dutch do not have a policy of vaccination of babies so they actually do a first time vaccination in their health care and we are doing revaccination. It will be interesting to compare and we've made sure that our results are collected in a comparable way at the end. We can pull the data and figure out if being vaccinated as a baby actually makes a difference to the vaccination if it's given to adults. There are other studies that are being conducted in Australia and I'm sure other people in this world will also try and do similar things in their countries. It makes sense to do this in different national environments where health care systems are different and pool the data afterwards. We must make sure we are neutral here. It might not work and if it does not work we must be honest about that. .Are you almost trying to disprove it?.That's a nice way to see it. We have set up the study so that both ways are possible. We have also set up the system in such a manner we call futility. Let's assume we have vaccinated a thousand people, 500 of them with a real vaccine and 500 of them with the placebo. If you observe them for a year and there is no difference then the committee can say, Okay you can stop observing it's not working. It would be disappointing but the study set up that we will find out either way..You mentioned a year, is that the time span that you're looking at or might you have conclusive proof one way or the other in a shorter period?.We have written in the initial protocol that we will observe people for a year. The course of this epidemic in this country will more or less dictate how much protection we could have measured in a year. This is impossible to predict. We have kept the protocol open so that we can amend it to observe people longer should we not have enough exposure to these health care workers to show a difference. We will record these events and the committees might then inform us if it would be worthwhile to keep observing these people for a bit longer. We would then interpret it as there being a weak signal that perhaps needs some confirmation. We can only decide once we see how quickly the epidemic evolves in South Africa and how far our healthcare workers will be exposed..Also read: Study that suggests BCG vaccine may protect against Covid-19 is flawed – TB experts.As a scientist, the last question is the most difficult one. What is your gut telling you about this? I ask this because there must be sufficient feeling that it's worth going ahead with this. Otherwise you would have perhaps looked at investing your time elsewhere..Yes, as a scientist you won't do experiments, especially experiments on people without having some degree of evidence that it might actually work. There's also animal experiments and other observations when BCG vaccination was used in studies that were looking at other things, and one was just always observing that there seems to be some protection that this BCG vaccination provides that is interesting. It was just never interesting enough to look at before we had this epidemic. It was one of these little blips out there that one makes a mental note of and thinks when I have time I will start looking into BCG and the moment that one has time just never comes. Now it has, and it is now the time to look at this. So it's not just a shot in the dark. There are at least five pages in our protocol initially that make a good case why one should try this and that it's not just putting people at risk. It's a minimal risk to have a vaccination for babies done in adults but still it's an intervention and ethics committees have agreed that there is enough evidence to make this a worthwhile experiment, that we have a good case and should urgently figure out if that protection is material or not.

BCG trials to see if it’s a shield against Covid-19 not just a shot in the dark – Prof Andreas Diacon

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