By Michael Le Page
Despite what you may have heard, although several potential drugs for covid-19 are being trialled around the world, few results have been reported yet, and we don’t know if any could help save people who are already seriously ill when diagnosed. Some enthusiastic news stories and claims being spread on social media are based on little more than anecdotal reports. However, the World Health Organization (WHO) is coordinating an international trial of the most promising drugs – and with case numbers soaring, we should find out soon if any of them work. “This trial focuses on the key priority questions for public health. Do any of these drugs reduce the mortality? Do any of these drugs reduce the time the patient is in hospital? And whether or not the patients receiving any of the drugs needed ventilation or an intensive care unit,” said Ana Maria Henao-Restrepo of the WHO at a briefing on 18 March.
The WHO trial will include the long-used antimalarial drugs chloroquine and hydroxychloroquine, a new antiviral drug called remdesivir and a combination of two HIV drugs called lopinavir and ritonavir. The HIV drugs will also be tested in combination with an antiviral called interferon beta. On 22 March, several countries in Europe, including the UK, launched a collaborative trial of the same drugs, which will complement the WHO effort. There has been a tremendous buzz about chloroquine after it was highlighted first by entrepreneur Elon Musk and then US president Donald Trump, who wrongly claimed it was already approved in the US for treating covid-19. There is some evidence that chloroquine and the closely related hydroxychloroquine are effective against related viruses such as the one that causes SARS. There have also been reports from China that chloroquine is beneficial when given to people with covid-19 associated pneumonia, but the findings have yet to be published. “It looks promising,” says Robin May at the University of Birmingham, UK. However, some excitement over these drugs stems from a study of just 42 people in France that said those who received hydroxychloroquine cleared the coronavirus from their bodies days faster, with the effect being even greater in those also given the antibiotic azithromycin (medRxiv, doi.org/dqbv). The researchers speculated that hydroxychloroquine can prevent infection as well, but other researchers say the small size of the study and other issues mean we can’t rely on its results. What’s more, while hydroxychloroquine and chloroquine are safe when taken properly, there are already reports of people overdosing on chloroquine in an attempt to protect themselves, which can cause lethal heart problems. Meanwhile, people who need this drug for lupus or arthritis are finding it hard to get hold of. Even if chloroquine does stop people becoming severely ill if given when symptoms are still mild, it wouldn’t necessarily be a game changer. At the moment, most countries are detecting coronavirus infections only once people develop severe symptoms, so what we urgently need is a drug that can save lives at this stage. “Whether that’s going to crop up is anyone’s guess,” says May. Unfortunately, it already seems that the lopinavir and ritonavir combination doesn’t do this. A randomised trial in China found no evidence of any benefit (NEJM, doi.org/ggpcms). As for remdesivir, the results of trials in China haven’t been made public yet. Many other potential treatments are being explored, particularly the possibility of developing antibodies against covid-19. Antibodies are the proteins our immune systems use to kill the virus, but it takes weeks for our bodies to ramp up production after we are infected. In theory, injecting antibodies made in a factory should be an effective way to both prevent and treat covid-19. US company Regeneron says it has already identified hundreds of antibodies against the coronavirus and plans to start mass-producing the most potent ones in mid-April. Another way to get antibodies is to extract them from the blood of people who have recovered from covid-19. At least 250 people in China have received treatments made this way. According to the Xinhua news agency, it was safe and effective, but the findings don’t yet appear to have been published. All the approaches described above are based on trying to kill the virus or prevent it replicating. However, it appears that most deaths from covid-19 are the result of a severe immune reaction called a cytokine storm. So another path is finding ways to prevent or dampen this response. A small study in only 19 people suggests that an immunosuppressive antibody called tocilizumab is highly effective (ChinaXiv, DOI: 10.12074/202003.00026). This approach can be risky, though. “Immunotherapy is really challenging because you’re messing with the immune system of people who are very sick,” says May.