Covid-19 vaccine trial brings SA great hope as virus storm intensifies: Prof Martin Veller. LISTEN!

There are nearly 150 vaccines under development in the world for Covid-19. The frontrunner appears to be a vaccine that is being developed by the Jenner Institute at Oxford University, which is being trialled in humans in the United Kingdom. AstraZeneca, which is producing the vaccine for the university, is so confident it will work that it has started beefing up production to have available 100 million doses in October. One of the concerns about the development of vaccines is that countries like South Africa will be at the back of the queue. South Africa has, however, now been given the opportunity to trial the Oxford Covid-19 vaccine. The University of the Witwatersrand started human trials this week. This is not the only South African link to the vaccine. Sygnia has shares in OSI, the company that transforms patents from Oxford University into viable businesses and is behind the Oxford vaccine. The Dean of the Faculty of Health Sciences at the University of the Witwatersrand, Prof Martin Veller told Biznews about the importance of trials in African populations. He gave an assessment of how our health services will cope with the rapid increase in coronavirus cases that the country is experiencing. – Linda van Tilburg

We are well aware of how important it is that the global south is involved in all of these trials. The one reason that you’ve indicated is that it does give us access to these medications, and that’s something that we learned in the early HIV days; that one had to be really actively involved to be able to present those kinds of therapeutic options to our patients. The second is, obviously, that we do know that there are variations in terms of response to various interventions – pharmaceutical and vaccines – across the world, and that one needs to test across a wider spectrum of people than what one normally would do, and clearly, there’s a richness of the information that if one is doing the study outside of the UK and in fact, I understand that this study is going to be done in Brazil and in the UK as well. So, it is to look for that broader view. 

And then there’s the one other area, which is a small part of this trial, but which is an important one from our perspective, and that is; what happens to an HIV infected population or a population living with HIV. As you know, about 15 percent of our South African population has HIV. Clearly, it is an important component.

There always are concerns that people who have HIV, even if they’re being adequately treated, are going to respond differently to these immunogenic treatment options. The one good thing that we have is that Covid is not a major drive in HIV. It increases the risk slightly, but it’s not as bad as one would have thought it could be. But we do need to understand the safety of this vaccine in an HIV population and also its effectiveness, and therefore, a small part of the study is going to be that. 

We have very active vaccinologists. Shabir Madhi – who’s the lead investigator in this – is a person who’s worked in the vaccine field over a long period of time, has been very involved in the development of vaccines and in the innovative use of vaccines – particularly in under-resourced environments, and has had a remarkable effect in terms of reducing the mortality, particularly in infants under two years of age in really very poor communities. Things like pneumococcal disease, the infant diarrhea’s and so on, made a big impact in terms of mortality. We have the expertise and between him and Helen Rees; they run this institute that’s part of our faculty called ALIVE – the African Leadership in Vaccinology Excellence Unit – and have been very involved in some of the other developments and are very interested, for instance, in the development of HIV immunological interventions and, to a lesser degree, in TB. 

What is the age group of people that you are going for? Because Covid-19, as you know, is a problem with elderly populations. So the first phase of the trial is for healthy individuals? 

No, absolutely. So, the trial is starting in adults and in non-HIV infected adults and then non-pregnant women as well. So, it is really – in the first instance – to try and get an understanding of what happens in a relatively normal (and normal is always an interesting term) population and is a randomised controlled trial, as one would normally do. The placebo in this case is saline, and again, it’s a question of seeing what the rate of infection between the two groups is. The patient selection, I’m told, is to go to places where there are hot spots, so that one does have the value of an increasing risk of infection, which is what one requires. Obviously, we don’t want people to become infected, but in this situation, what one is studying is the effectiveness of preventing infection. 

The study has been powered to ensure that if there is a 60 percent reduction in terms of the infection rate in the vaccine group, that that is likely to be picked up. The obvious other aspect about the study, which is important, is that it needs to look at safety. While we already know that several thousand people have been entered into a trial in the UK, obviously one wants to increase those numbers and wants to watch those people very carefully. As we know, vaccines across the world have had some side effects. This is one where – probably in the newer technologies – the level of side effects are going to be lower and where they’re going to be temporary. But again, one never really knows until one has really checked that out very carefully. 

So do you expect some differences in how population groups in South Africa would react to it? Are they expecting that a typical European profile would be different to a profile of an African citizen in South Africa? 

I think that there is always a risk that there are some differences; until we’ve really looked at it – we don’t know. If one just looks at the responses to the coronavirus – there appear to be modest differences across populations. And what the background to that is – is not clear. The fact that we are talking about an ace receptor, for instance, as being the important component of the virus being able to transmit through membranes… We do know that there are some variations across populations in terms of ace receptors. But that’s purely speculative on my part – one just needs to do the testing and be sure that there is no difference. And if there is a difference, that one then starts looking into the reasons that there might be.

Is the prevalence of HIV one of the reasons why they prefer to roll it out in South Africa?

I can’t answer that directly. I think that it’s important that one does find something that probably immunises our population or at least develops immune competence in our population, because of the concerns. But again, until we’ve really checked that out – we don’t know. 

When would it be able to be given to a large population if it works? 

Even if we have a very early answer – let’s say in the next three or four months- there’s still a significant period beyond that. And certainly, even these people who are working on the trials are saying that it’s highly unlikely that we’re going to have a vaccine before the latter part of next year, although there are people who are obviously pushing. Which then really asks us why is one chasing a vaccine, and the answer to that is quite simple; is this virus going to be around with us for many years to come? 

Can we look at – generally – just at Covid-19 and what is happening with the pandemic in South Africa at the moment – it seems that cases are increasing. Are we at the peak? What is happening in the Gauteng area where you are? 

We are undoubtedly – both in Gauteng and in the Eastern Cape – in a very significant upswing. We’ve also had quite a substantial increase in numbers in the last week. So, we clearly are going up and we’re going to be going up quite steeply in the next bit of time. What I’m hearing on the ground, in terms of hospitals, is that the hospitals in Gauteng are filling up. My understanding is that there is a fair amount of stress still in the Western Cape, but they seem to have generally coped, although they’ve had to go into resources outside of the traditional base. 

I’m hearing that the hospitals here in Gauteng are such that they’re not going to be able to take in a massive additional load. That’s not factual information, but hearsay. And then the one area that we do know that there are problems already is in the Eastern Cape, where the facilities are substantially less; much fewer hospitals, much fewer ICU beds. And I’ve certainly seen one of my co-Deans making serious pleas that the broader health system in the Eastern Cape comes together to work together in order to cope with what sounds like quite a significant crisis. Where are we expecting peaks? I mean, certainly the models that are working within our faculty and our university and in other parts of the country think that we are a longish way away from a peak. We certainly are going to be in for a run of four to six weeks. 

The only anything that I think might be helpful is that we probably have underestimated the number of people who are infected in this country. Shabir Madhi – he’s convinced that we probably have 10 times as many people infected in this country than is actually recorded, and that’s not that surprising. Firstly, we know that we don’t know what the asymptomatic infection rate is in this condition. I don’t think anybody really knows it in the world. But the other is that; the sudden, very significant upswing in terms of infections in Gauteng means that there’s a base that is probably significantly underestimated. It’s not because people are wanting to under-report it, it’s just that we’re not testing enough (I think), and I think we may well be dramatically underestimating the amount of asymptomatic infections.

Even though cases are tracking up fast now, the hospitals might not cope as well. Do you expect a lower fatality rate than European countries which have an elderly population? 

Very hard to predict. I don’t think that we’re going to find that we’re going to be all that different to the rest of the world. And I think that what we are going to find is that we do have a younger age group of people with comorbidities. We’ve got a significant prevalence of diabetes in many of our populations. We are still not totally sure about what happens with HIV. Hypertension is quite common in our countries. So, one thing that we have already noted is that the mortality spectrum in terms of age is probably 10 years younger in South Africa than in other parts of the world. So, I’m not sure that we can answer that. 

I do think we’re going to be hit like most other countries. I think we’re going to have to look at what the influence of health resources is going to be like. The one thing that is clear is; countries in which health resources are well organised seem to have had slightly better mortality rates. I’m looking, for instance, at Germany compared to maybe Italy and France and Spain. But again, this comparison of country to country and region to region is covered by so many unknowns that I think one just has to be fairly careful about making any serious conclusions initially from the information, and secondly, from making any serious predictions. 

You are a health sciences expert. What about treatments? That has progressed quite well – how Covid-19 is being treated, because I remember in the beginning – in the U.K – when you went into the ICU and you were on a ventilator – you had a 20 percent chance of getting out of there. Have treatments improved a lot? Have you learned a lot from what was happening elsewhere in the world? 

Well, I think we have. I think that what was really quite interesting is firstly how the academic world has been sharing information – that is quite interesting. I have a number of colleagues in Italy – vascular specialists who were talking to me about the thrombosis that is associated in all that is found in this condition. And very early on, we’re saying, that we needed to treat the thrombosis as a significant component. And I think that that’s been the situation around the issues related to diagnosis, related to the treatment of the pneumonitis, that’s been related to the treatment of the other associated organ failures and things like that. So, I think it’s been a steep learning curve. It really is remarkable how much information was accumulated out of the European and UK experience and how incredible our colleagues have been in terms of sharing this. Certainly, what we thought was the treatment mantra in February changed by April and again in May – and it’s been the sharing of information. 

The dexamethasone trial is an interesting one, which I think was great in the sense that that’s now a randomised trial, so we’re now getting to the point where one is using the usual standard of information that we like in clinical medicine to understand what’s going on. And I hope that we are going to have more and more of these kinds of trials being put into place. Some that have been obviously quite probably unnecessary. I mean, the whole question of trying to put together chloroquine trials and things like that. The French were the people who did it, and I think the one component in that trial which sounds like it’s got some value is remdesivir – and that might be something interesting – although its effect is not as much as we thought it would be. And I must say that the only real massive benefit has been in Gilead’s share price. 

South Africa is in for quite a rough ride now, and it might be a problem that our hospitals might start to overflow in some provinces. 

We are in for a tough time. I think we are going to see the devastation that you’ve seen in your parts of the world. It’s just a matter of when, not if. But I am really quite comfortable with how the early phases of this pandemic have been managed in South Africa in the sense that we’ve been able to get some of our ducks in a row. It’s had a significant effect on our economy, unfortunately, and we are going to – sometime down the line – have to try and work out how much value we got out of that. Certainly, a group of academics in our university, non-partisan, is starting to wonder about that quite seriously. But again, it’s always easier with hindsight, not with foresight.