COVID-19 treatments called into question

02 June 2020

Interview with 

Anthony Davenport, University of Cambridge

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Drug bottles held in a doctor's hand

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There was optimism when UK Health Secretary Matt Hancock announced that a drug called remdesivir, which appears to shorten recovery time by about four days for people with Covid 19, is being made available on the NHS. The Health Secretary said it was probably the biggest step forward in the treatment of seriously ill patients since the crisis began. On the other hand it turns out a drug being touted, and taken, by President Trump isn’t reliably good after all. The effect of hydroxychloroquine has been called into question after an analysis by American researchers who say it might even make things worse. While their study has limitations - particularly the fact that they looked at the drugs’ effects at very high dose - the World Health Organisation has suspended trials of hydroxychloroquine, along with those of another chemically similar drug called chloroquine. The research has been published in the Lancet medical journal, and Phil Sansom has been discussing the drugs with Cambridge University pharmacologist, Anthony Davenport...

Anthony - Both of them are antimalarial agents and it was originally thought that they might have some benefit in patients with COVID-19.

Phil - Why, how do they work?

Anthony - I think the way they work is unclear, although it is thought that because the virus is taken into very specific organelles within the cell, which are acid, these two drugs are thought to change the pH or acidity, to make them more alkaline. So they're less likely to gain entry.

Phil - Tell me about this Lancet study. How did they investigate this?

Anthony - So it's important that people who are actually on many of these drugs continue to do so. And if they've got any concerns, they should talk to their doctor. But what this group did was to look up the patients records from over 600 hospitals around the world, and they really looked at four different groups. These were the two drugs on their own, or the two drugs in combination with antibiotics.

Phil - So these are people who got coronavirus, were already taking hydroxychloroquine and chloroquine?

Anthony - Yeah. So what they asked was: the patient had to have evidence that they had the virus, and they used as their control from these four groups, about 80,000 individuals who were on other treatments. And they also excluded patients who were on ventilators. So in other words, they were looking at people who had an early diagnosis and were not particularly sick.

Phil - And what did they find?

Anthony - Patients who are taking one of those four drug treatments actually had a significant increase in deaths in hospital compared to the control group.

Phil - Do we know then whether hydroxychloroquine and chloroquine are dangerous, if you've got COVID-19?

Anthony - We can't conclude that. But what it says, there doesn't seem to be really any evidence of benefit. One of the limitations of this study was that obviously, they didn't set out to carry out out a clinical trial, where you would have different concentrations of the medicines that you were testing. In this case, it looks as though the concentrations of some of the medicines may have been too high. So it's important to bear that in mind. But what it does suggest is that there should be some more testing of these compounds, to make sure that they are safe at the concentrations that they're being used.

Phil - What should I make of this? Is this, sort of, showing the limitations of a drug that hasn't been tested yet?

Anthony - Yes. I think it's very important that, as I emphasised, the drugs are normally used for very specific diseases and they've been shown to be safe and effective. This is a completely new clinical indication. We don't really understand the mechanism of how the virus does so much damage.

Phil - Now there's been news here in the UK about another drug called remdesivir, what is it?

Anthony - It's basically a nonspecific antiviral agent. In other words, it tries to stop the virus reproducing. It mimics some of the residues, which are in the virus, and it prevents the virus from replicating. What they've allowed is that clinicians are able to prescribe the drug, but there is no evidence yet that this drug is an efficacious drug in the setting of patients with COVID-19. A large clinical trial in the United States has suggested that there was a reduction in time to recovery, but we don't yet know whether or not there's going to be any longer term benefit.

Phil - What kind of benefit are we talking? Is it fully treat, help a little bit?

Anthony - I think if we think about other viruses, such as HIV-AIDS, generally, it's a cocktail of drugs. So you may wish to combine it with other drugs, which reduce the severity of the symptoms, but it's unlikely on its own to be a game changer. It's not going to be a magic bullet.

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