COVID critical care: what we know now

When Donald Trump caught the coronavirus his doctors put him on a range of treatments, including an experimental antibody therapy from the company Regeneron as well as a number of other drugs and supplements. It’s been unclear how ill he actually is, so it's difficult to judge whether these measures were appropriate; but how do they stack up against the current best practice in COVID treatment? And how much have we learned since the pandemic began? Charlotte Summers is an intensive care consultant at Addenbrooke's Hospital; she also advises the UK government on managing the condition. Chris Smith asked her opinion on Trump's treatments...

Charlotte - I have to say I was quite surprised; they perhaps weren't the first drugs necessarily that I would have reached for had I been one of the doctors looking after him. I think the most controversial is probably the Regeneron therapy that he had, which is a cocktail of two antibodies that are designed to neutralise the virus. And actually the company that makes those had only released the first data on this a few days before they were given to the president, and it was only based on 275 patients, and the clinical trials are ongoing. We don't actually know whether this therapy works or not. So I was slightly surprised that a very experimental therapy - which although it looks promising, isn't proven - was given to the president of the United States.

Chris - The rationale for using antibodies is, of course, that's what your own immune system makes when you have an infection; and if you give people those, perhaps it will help to soak up some virus and bolster your own immune response. Have we not though seen something of a checkered response to the convalescent plasma therapy that has been done for some time since this began, where people are taking blood products from people who have recovered from coronavirus and giving them to people at high risk of severe disease, and it's not clear that that's actually working? So why do we think these Regeneron... or I know AstraZeneca are also making a rival product, aren't they? Why do we think that this is actually worth pursuing?

Charlotte - The issue with convalescent plasma is that everybody makes a different level of immune response. Some people make a very low level of antibody response; some people make much higher. And lots of the data that's been generated with convalescent plasma studies has not been terribly clear about the amount of antibodies in the therapy that's being given. But convalescent plasma has been given by two big trials in the UK that are ongoing at the moment, the RECOVERY trial for people who are hospitalised and the REMAP-CAP trial for people that are in intensive care. So we should get an answer from those fairly soon, I hope. The antibody therapies: we know how much antibody you're given, and we know that they are targeted to try and neutralise the virus, so it's slightly different type of antibodies to the general antibodies you might make in your new plasma in response to having had the virus.

Chris - So there's a slightly higher prospect that they may be advantageous. The other thing that he got was dexamethasone- tell us a bit about that.

Charlotte - Dexamethasone is a steroid treatment and that's quite widely used across a range of healthcare settings. But what was important was that this therapy is one that's got an evidence base. The big UK clinical trial called RECOVERY, that lots of people will have heard of, showed that there was a mortality benefit in people who needed oxygen or who were on ICU ventilators if you were given dexamethasone; so their outcomes and their chance of survival were improved by having this therapy. People who weren't on oxygen: there was definitely no benefit, and possibly even a potential that the therapy did some harm in that group of people. So I can't imagine that they gave the dexamethasone therapy to Donald Trump without him requiring oxygen. And we know that the reports about whether he did or didn't require oxygen have been a little bit confusing at times.

Chris - Theo, you must have been party to quite a lot of data coming across your desk on drugs, including dexamethasone?

Theo - Yes. I think at the moment there are several hundred trials of different drugs and therapies ongoing, and there's also been a lot of claims based on observation, because so many people have been hospitalised and some of them happen to be taking drugs for something else. For example, there was a suggestion that one particular antacid that people take if they have stomach problems... people taking that in China, in the first wave of COVID, appeared to do slightly better than people who weren't taking it. And actually that's one of the cocktail of drugs that Donald Trump seems to have been given, although he may have been taking it anyway.

Chris - This is famotidine, isn't it? The ranitidine-like drug?

Theo - Yeah. But he may have been taking that anyway for some other condition; we don't know. They seem to have sort of thrown a bunch of things at Donald Trump, some of which, as Charlotte said, you would expect to treat severe illness with; and some, like the antibodies, you would treat early in the illness; and it just adds to this confusing picture of how long he's been ill, how seriously ill he was.

Chris - And Charlotte, if you had been the physician to Donald Trump and you had to treat him or manage him, how would you have approached it? And also what have we learned about how, when someone comes in and they're acutely unwell with COVID, the actual disease caused by this virus, how we manage them now, compared to how we would have been managing people back in March?

Charlotte - It's slightly tricky to say exactly how I'd have managed him and get it right, because I don't have all of the medical information available to me. I've just got what's in the press. But I would definitely have started with the therapies for which we've got evidence. So if he needed oxygen, I would definitely given him the dexamethasone. And if he was early on, and had signs of pneumonia - inflammation in his lungs on a chest X-ray - I would have given him remdesivir, the antiviral therapy, that he did get, but a little bit later and after getting the Regeneron. And given that convalescent plasma actually has got an emergency use license in the United States, I would potentially have gone with that rather than the experimental Regeneron therapy. Although I would have tried to encourage him to be randomised into a clinical trial so that actually we could have learnt something about the use of these therapies, rather than just giving it on compassionate grounds.

Chris - What about issues with giving people supplementary oxygen early? And also this question about anticoagulation? We've learned, have we not, that quite a lot of people who get this infection have problems with their blood clotting going off?

Charlotte - I'd have given him oxygen if he needed oxygen. And actually there's advice across the world about the levels at which we should start giving people oxygen therapy that vary from between about 90 to 94%, depending on how well you're monitored. So if his oxygen levels had dropped to those kinds of levels, I would absolutely have given him the oxygen, because that's important. Anticoagulation is more tricky and there's actually not strong consensus across the community of hematologists and other healthcare researchers about what the best approach is here. We know that patients with sepsis from any cause actually have an increased risk of getting blood clots. And coronavirus infection, or COVID-19, has had a really big number of people with a sepsis type illness recently. So we've been seeing a lot of people with blood clots, but it's still not definite that the proportion of people with COVID getting blood clots is substantially greater than the people who have sepsis from other causes, but I think it probably is. But we don't have data to back that up.

In terms of what we do about that, there isn't an evidence base to answer that question at the moment. There's an arm of a trial called REMAP-CAP that is looking at hospitalised ward patients in the UK to try and come up with an answer for that. And there are other trials in discussion across the world. But it's something that we don't have good evidence for. Should we give them things like aspirin? Should we thin the blood therapeutically? Should we just give them protection against developing clots? What's the best way to go? It's still a subject of great debate.