Several hundred trials of potential treatments for the coronavirus are around the world. Early results suggest a few might slightly reduce the risk of dying from covid-19, but we won’t know for sure until larger trials have been completed.
“The good news is that there is a lot of activity,” says Trudie Lang at the University of Oxford. “Sadly, however, we don’t actually have anything that works as yet.”
There are two main approaches. One is to try to reduce the damage done by the virus, such as by preventing the immune overreaction known as a cytokine storm that is thought to kill many of those who die of covid-19. The idea here is to prevent the immune response ramping up to such a high level that it starts damaging the lungs and stopping people getting enough oxygen.
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Many different immune signalling molecules, or cytokines, are known to be involved. We have already developed drugs that specifically block some of these signals – for example, to treat autoimmune diseases such as arthritis.
One such drug is tocilizumab, which blocks the receptors that respond to a cytokine called interleukin 6, or IL-6. Several initial studies suggest it can somewhat reduce the risk of dying when given to those severely ill with covid-19.
For instance, in involving 100 covid-19 patients in intensive care, some of whom were on ventilators, 61 per cent of those given tocilizumab survived compared with 48 per cent in the control group. However, this was a retrospective study. We will have to wait for the results of a larger, randomised , the manufacturer of tocilizumab, to find out if it really works.
Numerous similar trials are getting under way. For example, pharmaceutical firm of canakinumab, which blocks another cytokine called interleukin 1 beta, or IL-1β.
There are inherent risks in trying to dampen down the immune response in people with a viral infection, says Babak Javid at Tsinghua University in Beijing. One solution could be to give people antiviral treatments at the same time, he says.
This would target the virus directly using drugs that block its replication or antibodies that bind to it and trigger its destruction. It is this antiviral approach that has been getting most of the research attention. In particular, an old malaria drug called hydroxychloroquine has taken the spotlight thanks to US president Donald Trump, who has promoted it. But it is becoming clear that hydroxychloroquine doesn’t improve outcomes and can have serious side effects.
“I think it’s fair to say that every rigorous study that’s looked at hydroxychloroquine has shown no benefit,” says Javid. The largest study yet compared outcomes in 15,000 people with covid-19 given either hydroxychloroquine or the closely related drug chloroquine, with those in 81,000 patients who got neither. It found no evidence of benefit. However, this was not a randomised trial.
For another antiviral drug called remdesivir, the results are more encouraging. According to an announcement on 29 April by the National Institutes of Health in the US, those given remdesivir recovered faster and were slightly less likely to die – 8 per cent versus 11.6 per cent for the control group – during a randomised trial involving around 1000 people.
However, the reduction in mortality wasn’t statistically significant. More than two weeks on, many researchers are puzzled by the failure to reveal the full results from the remdesivir trial.
There is also a serious problem with all antivirals, including those that use antibodies. Some antiviral drugs might work if given soon enough after a person contracts covid-19, but we aren’t going to find out by doing trials involving those who are already severely ill, as is currently the case, say both Lang and Javid.
“Anything that works by targeting the virus will be less effective later on [during a person’s illness],” says Javid.
Even if we do find an antiviral that works if given early, its widespread use would depend on being able to detect infections early and treating those at highest risk. Yet most countries aren’t detecting infections early on, nor do we have good predictors of who is going to develop serious disease, says Lang.
Javid remains optimistic. “It’s remarkable what progress have been made in a very short space of time,” he says. “We will have some form of combination therapy that does something.”
Lang is less certain. “The fact we have not had any early successes may mean we are not going to find a magic bullet,” she says. Developing a transformative treatment may require starting from scratch rather than repurposing existing drugs, which could take years.
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