How medicines for arthritis, the flu and herpes are helping to treat Covid

Since the beginning of the pandemic, the world’s media has become understandably fixated with the race to find a vaccine. The Phase Three trials carried out by Pfizer/BioNTech and Oxford/AstraZeneca were pored over like no other medical experiment in history, and the news that Margaret Keenan, a 90-year-old grandmother, had become the first person in the world to receive a clinically vetted Covid-19 vaccine outside of a trial was met with understandable exhilaration, reducing the Health Secretary to tears live on television.

But vaccines are not our only weapon against the virus. Running concurrently with the urgent race to find a vaccine has been an equally important – if less glamorous – race to find drug therapies to treat patients who have already contracted the virus. Doctors have found most success by repurposing drugs that already exist. Many of these under-the-radar medicines have been used for years, or even decades, to treat conditions as diverse as arthritis and hepatitis-C, but are now finding a new lease of life in the battle against Covid.

“From scratch, a drug can take up to 15 years to make and get licenced,” says Dr Stephen Griffin, Associate Professor in the School of Medicine, University of Leeds. “So if you have something that's been through that process and shown to be safe in people, and you're faced then with an imminent health crisis, then... you’re able to deploy that drug much more quickly. It’s basically a question of time, money, and regulatory approval.”

Dexamethasone

In the early weeks of the pandemic, doctors on Covid wards noticed that many of their severely ill patients were suffering from hyperinflammation, where the body’s immune system goes into overdrive, inflaming body tissue to dangerous levels in a misfired attempt to create a hostile environment for the virus. This “cytokine storm”, say doctors, is a leading cause of death.

Dexamethasone – known sometimes by its brand names Neofordex, Glensoludex, and Martapan – has been used since the Fifties to treat various ailments caused by the body’s immune response, including anaphylaxis, skin swelling and autoimmune conditions such as lupus. It works by blocking infection-fighting white blood cells from travelling to the area of swelling in your body.

The strongest evidence for its efficacy against Covid comes from Oxford University’s RECOVERY trial, in which 2,000 Covid patients across 175 NHS hospitals received a daily 6mg dose of the steroid. Their outcomes were compared to 4,000 patients who were not given the drug. Dexamethasone reduced deaths by one-third in patients receiving ventilation and by one-fifth in patients receiving just oxygen. There was no difference in patients with mild illness.

Baricitinib

Whilst dexamethasone is the most promising, other anti-inflammatories are gaining traction.

In a small study of 83 seriously ill Covid patients across Italy and Spain, for example, researchers at Sweden’s Karolinska Institute reported last month that the steroid baricitinib (marketed as Olumiant), first developed in the 2010s to treat rheumatoid arthritis, reduced deaths from Covid by two-thirds. Crucially, the study included elderly patients – the group most likely to die from Covid, but one that is often excluded from trials for safety reasons.

Remdesivir

Whilst anti-inflammatories like dexamethasone tackle the body’s response to the virus, antivirals like remdesivir attack the virus itself. Developed in the 2010s by US pharmaceutical firm Gilead Sciences to treat hepatitis-C, the drug was first repurposed in 2014 to fight the Ebola epidemic, where it showed promising results. Those trials in west Africa proved that remdesivir was safe to use in large numbers of people, allowing researchers quickly to repurpose the drug once again when SARS-Cov-2 (the virus that causes Covid-19) emerged in Wuhan, China, earlier this year.

Coronaviruses are made up of ribonucleic acid (RNA). In theory, remdesivir interferes with a key enzyme in the body needed to replicate RNA, preventing the virus from multiplying.

At first, doctors reported promising results and a trial of 1,063 hospitalised Covid patients, carried out in the spring by the US’s National Institutes of Health, showed that patients given a five-day dose of remdesivir enjoyed quicker recovery times than those given a placebo.

But last month the World Health Organisation (WHO) threw a spanner into the works, when its Solidarity trial, which involved thousands of Covid patients across the world, found remdesivir to have no meaningful impact.

Even so, in October the influential US Food and Drug Administration approved the antiviral to treat Covid in hospital.

“It’s a conundrum,” says Dr Griffin. “You've got these two conflicting trials, one of which [the WHO trial] is much bigger than the other. We need more trials to resolve this.”

Favipiravir

Another anti-viral, favipiravir was developed around 2014 by the Japanese photographic firm Fujifilm after it branched out into pharmaceuticals. It was first designed to treat the sexually transmitted illness herpes, but was later found promising against influenza.

The evidence for favipiravir’s efficacy against Covid is fairly mixed, says Dr Griffin, and most doctors think it probably does not work as well as other antivirals like remdesivir. Trials in Japan and China suggested the drug could quicken recovery times for Covid patients – but these studies were small, and researchers often combined the drug with other antivirals.

But, crucially, favipiravir can be taken as a tablet, whilst remdesivir usually has to be administered in hospital through an intravenous drip. It means that, pending the outcome of future trials, favipiravir could potentially be taken at home by patients with only a mild case of Covid.

“The jury's out on favipiravir. There's not been solid data either way,” says Dr Griffin.

Vitamin D

The “sunshine vitamin” is a naturally occurring substance – unlike the synthetic drugs listed above – but is worth mentioning here because of the long-held evidence that it helps protect against viruses, especially respiratory infections, by increasing production of antiviral proteins and decreasing the production of cytokines, the molecules that cause dangerous inflammation. It has long been suspected that high rates of Vitamin D deficiency in winter are part of the reason for seasonal flu outbreaks.

Evidence is so convincing that last month the Government announced it would deliver free Vitamin D supplements to three million clinically vulnerable people and care home residents – although the NHS says there is still not enough evidence to say definitively that the vitamin works against Covid.

Dr Griffin stresses that Vitamin D supplementation is most likely correcting a deficiency rather than tackling Covid itself. “It’s not quite the same as giving a drug therapeutically against the virus, but it certainly is a good thing to make sure people have it. It’s been shown to be important in your immune response to respiratory infections.”

And crucially, he adds, most people in the UK are deficient in Vitamin D. Indeed, Public Health England (PHE) advises everybody older than five to take a daily 10mcg supplement of Vitamin D between October and March, to make up for the lack of sunlight.

It means that Vitamin D  just might provide a useful weapon against the virus. “It will certainly not do any harm,” says Dr Griffin.