Nicholas White on the use of chloroquine and hydroxychloroquine for prevention of COVID-19

Nicholas White has been one of the few lucid, balanced voices on the use of chloroquine and hydroxychloroquine in treatment against COVID-19.

He is co-principal investigator of COPCOV, a randomised, placebo-controlled prophylaxis study to determine whether those drugs prevent the novel coronavirus disease in the healthcare setting.

In this video, recorded in July 2020, he says that we still don’t know if chloroquine and hydroxychloroquine work and that it’s been hard to find out because the politicisation has been interfering with the conduct of the studies.

[UPDATE – 11 August] Read the full transcript below the line.

The COPCOV study is a study which is going to try and find out whether healthcare workers and people working in the healthcare sector could be protected against COVID-19 by taking either hydroxychloroquine or chloroquine.

These are very old and well-established drugs that have been used for nearly 60 years for the treatment of malaria and various rheumatological conditions. But they came into prominence about six months ago because they also have antiviral activity. And so studies were started in many places to see whether these drugs would be effective.

Unfortunately, as probably many of you if not all of you know, they then became extremely politicised, and that has interfered seriously with the conduct of the studies that are needed to find out whether the drugs work or not.

So this is an update in the middle of July to say where are we now with these drugs.

Well, after the initial enthusiasm or hype, there came a serious reaction. And a lot of this was promoted by a study that was published on May 22nd by The Lancet which claimed that hydroxychloroquine and chloroquine used to treat COVID-19 were dangerous, that they actually caused heart arrhythmias and killed people. Now it turns out that that study was fabricated. Completely false. And it’s been retracted. But it created enormous problems. Many regulatory authorities overreacted, stopped trials, and the general perception came that these drugs were dangerous and didn’t work.

Then came very important information – in fact the only really clear information on medicines to date in COVID-19 –, and that came from the UK Recovery trial, which showed that high-dose hydroxychloroquine did not benefit people who were in hospital receiving oxygen or being ventilated with COVID-19.

That led people to conclude, reasonably enough, they didn’t work at all, but that’s not fair. It’s becoming increasingly clear that, by the time people get into hospital and are very sick, it’s the inflammatory or immune damage that causes the problems and may kill them. And that’s why steroids – dexamethasone – are beneficial in that phase of the disease, whereas the virus in the body multiplied much earlier.

So we’re beginning to believe that the earlier you can get in and stop the virus multiplying, the better, and that would mean antiviral drugs; whereas for the severely ill patient in hospital, it’s more the inflammatory reaction and other complications that may lead to their death.

So that still means that chloroquine and hydroxychloroquine could prevent or perhaps even treat early in the course of the infection.

Now, there have been a few trials published in the medical literature and they give a confusing picture. Some show no benefit, but others do show benefit – they indicate that hydroxychloroquine or chloroquine can either treat or prevent COVID-19.

There have been some very small studies in the laboratory, and the picture is just unclear. And when we have an unclear picture, the only really good way to resolve this is through a randomised controlled trial, and that is what the COPCOV study set out to do and still aims to do.

In fact, we can summarize the situation by saying we are no clearer today – and that is four months after trying to start this study – than we were at the beginning.

It’s quite possible that chloroquine and hydroxychloroquine can prevent COVID-19.

Now, this is a very large study, and it’s a large study for a very good reason, and that is because we don’t think these drugs are very strong antivirals. In fact, they’re quite weak, so we’re not expecting miraculous effects. We’re expecting a small but useful benefit, which might take the edge off the infection and may well stop people getting into severe disease.

Now, to find out a small effect, you need a very large trial. And if we look at nearly all the other trials that have been done, with the notable exception of the UK Recovery trial, they’re all very small. So they could only pick up very big differences, which are implausible and unlikely.

The other area of concern has been safety, and there have been some exaggerated statements and claims, and some of which are just frankly wrong.

There’ve been claims that chloroquine and hydroxychloroquine cause blood toxicity – this is absolutely wrong. Yes, they do affect the heart, and taken in overdose they’re dangerous. But the evidence from the trials to date in COVID-19 and the enormous experience in malaria and rheumatological conditions strongly suggests that they’re safe at the doses that we’re evaluating at the present time.

So if we summarize all the information we have to date, I could say we still don’t know whether these drugs could prevent COVID-19, and we really need to find out, and we’re confident that the doses that we’re evaluating – which are the same doses that people have been taking for decades in rheumatological conditions – are safe.