In the early days of the pandemic, when even optimists thought a vaccine might be five years away, the world was desperate for a way to prevent serious cases of Covid-19. Enter hydroxychloroquine. The hype surrounding the decades-old antimalarial drug was spurred on by a shaky study out of France that suggested it as a treatment for Covid-19, and so people began to take it in droves, so much so that it led to shortages of the drug. The then US president Donald Trump announced that he was taking the drug as a precaution, causing a 1,389 per cent spike in searches for where to buy it.
Then, just as soon as we learned to spell hydroxychloroquine, the drug fell from acclaim. Following concerns about its safety, trials began to halt and emergency use authorisation of the drug was revoked by health authorities in the US and UK. The final nail in the coffin was hammered in by the UK Recovery trial in June 2020, which showed that the drug did not improve recovery in hospitalised patients. The World Health Organisation (WHO) guidelines on drugs for prevention of Covid-19 currently strongly recommend against using hydroxychloroquine in individuals who do not have Covid-19.
Despite the controversy over hydroxychloroquine, the need for drugs that might prevent Covid-19 hasn’t gone anyway. A flurry of new viral variants, suspended vaccines and a sluggish vaccination rollout in parts of the world means that the vaccines may not be a cure-all – and another defence in our arsenal could be crucial.
“Hydroxychloroquine went from hero to zero very quickly,” says Nicholas White, a professor of tropical medicine at Mahidol University in Thailand, who is one of the few remaining researchers who still plowing ahead with a hydroxychloroquine clinical trial, testing the efficacy of hydroxychloroquine and its sister drug chloroquine as a pre-exposure prophylactic treatment against Covid-19. His trial has faced massive difficulties in recruiting participants. White takes serious issue with the WHO’s recommendation against continuing clinical trials for the drug; while he acknowledges that there isn’t enough evidence to recommend the drug, there also isn’t enough to renounce it permanently either, he says. And he thinks it’s still too early to rule out the drug as a preventative treatment for Covid-19. “We are in a tug of war with the virus’ evolution,” says White. “And you need something else to buy time if the virus starts to win, and that is drugs.”
In March, the UK government announced the funding of two clinical trials testing prophylactic, or disease-preventing, treatments for Covid-19, one in care homes and the other in people with compromised immune systems.
The first is trialling the tapeworm drug niclosamide in immunocompromised patients; specifically those on dialysis treatment, with a kidney transplant, or who have autoimmune conditions that require medicines to suppress the immune system. The trial, called PROTECT-V, is led by Cambridge University researchers who are looking for pre-exposure prophylactic treatments, or PrEP. PrEP works by interfering with viral replication by blocking virus particles from entering the cells, and thus prevents infection. It offers insurance against being infected – like taking blood pressure-lowering tablets to prevent strokes, even though you don't know whether you're actually going to get a stroke.
The trial team settled on niclosamide as it’s a drug that’s been approved for years, doesn’t interfere with any of the common medicines that these patients typically take and it can be administered easily via a nasal spray, says Rona Smith, a senior research associate at the University of Cambridge who is leading the study. The drug works by preventing the virus from replicating in the nasal epithelial cells, which are one of the earliest cell types that Sars-CoV-2 tries to take over.
Death rates in people on dialysis have been much higher than the rest throughout the pandemic; one in five dialysis patients who tested positive for the virus died within 14 days in the first wave in the UK. A preventative treatment for these people could be life-saving. These patients don't tend to mount as good a response to vaccines as healthy people, because their immune systems may not make very many antibodies. A study in organ transplant recipients who had received one dose of a Covid-19 vaccine found only 17 per cent had produced detectable antibodies against the Sars-CoV-2 virus. Many of these patients haven’t been able to leave their house for a year now, save for hospital appointments, Smith says. “What we're hoping for these patients is that their life could get back to some sense of normality.”
The second trial, called PROTECT-CH, on the other hand, is hunting for another type of preemptive treatment. Referred to as post-exposure prophylaxis, or PEP, it would be taken after being exposed to someone who has tested positive for the virus. While Philip Bath, its lead researcher at the University of Nottingham, can’t say exactly which drugs will be trialled, they will be ones that are already used in the NHS for other conditions.
The trial is targeting care homes, whose residents and their staff have suffered a colossal brunt of the deaths and illness throughout the pandemic; deaths in care homes have made up about a third of all fatalities involving Covid-19 in England and Wales. The biggest challenge in setting up the trial, Bath says, is getting access to care homes, which are often privatised, unlike the NHS system, and they don’t have much of a history of taking part in trials.
Considering at least a fifth of care home staff have not yet had the vaccine, combined with not knowing whether the vaccines work in the very elderly means that these facilities may not be able to afford to rely on vaccines alone. “You don't want to put all your eggs in one basket,” says Bath. “It's about trying to offer you another intervention so that if the virus does get into the care home, we can protect people who are particularly at high risk because they're sitting in the middle of the virus.”
While the vaccines have been one of the standout successes of science’s response to the pandemic, it’s becoming increasingly obvious that vaccination alone won’t be enough to curb the pandemic. “The vaccines are wonderful. But they're not 100 per cent protective, and there are sectors of the population which either cannot or will not be protected by them,” says Andrew Owen, a professor of molecular and clinical pharmacology at the University of Liverpool and author on the WHO’s guideline on drugs to prevent Covid-19.
If we could find a cheap, already-approved and widely manufactured drug – just like niclosamide – it could act as a band-aid solution for the low and middle income countries while they wait for vaccines, where rollout has been much slower. “That would be a huge win for humankind,” says Owen, who is supportive of the two UK clinical trials. “But whether we'll get there is uncertain, and that's why we need clinical trials like these and the others.”
White agrees these studies are imperative. “We do not know what's going to happen next. And to have something in the cupboard that you could go to to buy you some time while you develop a new vaccine for a variant or so on, that's really valuable.”
Grace Browne is a science writer at WIRED. She tweets from @gracefbrowne
This article was originally published by WIRED UK
