Still learning lessons from COVID

It was not long ago when families of hospitalised Covid-19 patients were frantically searching for a dose of remdesivir or hydroxychloroquine. These drugs were hard to come by, and their price surged.

Convalescent Plasma Therapy which uses blood from those who have recovered from an infection to treat new cases was similarly thought to be another effective regime for Covid patients.

Until that point during the Covid-19 pandemic, there were no working vaccines. Even when the first vaccines were produced, there were not enough doses for Nepal while the delta variant was sweeping India. Covid hospitalisation was at an all-time high, hospitals were running out of beds as even younger populations succumbed to the disease.

Today, these drugs and treatment regimes have been found to be completely ineffective.

A RECOVERY (Randomised Evaluation of Covid-19 Therapy) Trial started at Oxford University found that hydroxychloroquine was no good for hospitalised Covid patients. Surprisingly, the Recovery Trial also showed that it was a widely available cheap steroid called dexamethasone that was the most effective in some groups.

“Dexamethasone is the real winner by far, it is such an easy and cheap drug to use, followed by Tocilizumab and Baricitinib which are more expensive and difficult to access drugs but showed additional mortality benefits in severe patients,” said Peter Horby, infectious disease specialist and co-lead of the RECOVERY trial during a meeting in Kathmandu last month.

He added: “Aspirin, azithromycin, hydroxychloroquine, plasma therapy, colchicine and lopinavir-ritonavir had absolutely no effect on survival rates. In fact, there are potential harms of using hydroxychloroquine.” Hydroxychloroquine gained much momentum after then-US President Donald Trump endorsed the antimalarial drug for use in Covid patients.

The Oxford University RECOVERY trial with 49,051 patients enrolled and 189 sites with Nepal being the biggest only after the UK, is the largest randomised controlled clinical trial of Covid-19 treatments, more than twice as large as any other trial. It has so far produced clear answers on 13 different treatments, and no other trial has determined international treatment guidelines in the way RECOVERY has.

The major finding of the RECOVERY trial that dexamethasone reduces mortality among patients admitted to hospitals with Covid-19 who need oxygen therapy saved over 1 million lives globally just in 2021. But before the trial, there was uncertainty whether or not this treatment would work.

“Many well-known doctors actively discouraged the RECOVERY team against using a cheap steroid dexamethasone, but they had based their opinion on much smaller studies,” explains Buddha Basnyat, physician with the Patan Academy of Health Science and the Principal Investigator for the RECOVERY Trial for Nepal.

He adds: “But Peter Horby decided we need to do a trial that was sufficiently large to be able to conclude if the drug works, he cut through the fog of confusion and the British review board went with it. It was science at its best.”

The trial also demonstrated that powerful antiviral treatments such as monoclonal antibodies when directed against the virus could reduce mortality in patients who have not developed their own antibodies, which many doctors doubted would work.

In Kathmandu, Horby recalled meeting a South American minister and found out that they still had aspirin in their Covid treatment guideline. He said: “There is still work to do to get this information through the policymakers about what works and what doesn’t.”

The Covid-19 pandemic was an extraordinary global crisis, but in some ways it is similar to the tendency of governments to intentionally look for expensive and complex solutions to medical emergencies when proven cheaper solutions are available.

For example, Misoprostol is a cheap drug that can prevent maternal deaths from post-partum haemorrhage. It was a part of the program launched in the mid-2000s to protect women who give birth at home but now it faces opposition, neglect and shortages in Nepal because it is so cheap.

“Tranexamic acid is another cheap drug for post-partum haemorrhage. The same steroid for Covid-19 called dexamethasone is the most effective drug for the treatment of severe altitude illness,” says Basnyat, who specialises in mountain medicine. “There is a tendency to underutilise some of these affordable, simple and easily available lifesaving drugs at our disposal.”

The RECOVERY trial also turned out to help build medical research capacity in Nepal. The Infectious Diseases Hospital at Teku and the Armed Police Hospital were at the forefront while the Oxford University Clinical Research Unit Nepal spearheaded the campaign and convinced the Nepal Health Research Council to participate.

“Nepal played a crucial role in the expansion of the trial from the UK to the rest of the world,” Horby told Nepali Times. “Nepal recruited more patients than any other country outside the UK.”  

Indeed, Nepal was the single biggest contributor to the trial and the research contributed to the global science, and it was a big boost for fledgling research culture in Nepal.

Says Basnyat: “We stood to gain scientifically from this but also showed young doctors and nurses in Nepal were randomising patients in a very standardised way, learning new things despite the tragedy that was Covid-19.”

The RECOVERY platform has now transitioned into finding treatments and better care for pneumonia and other influenzas which still kill hundreds of thousands of people worldwide.

Added Horby: “RECOVERY has shown the benefit of large, streamlined trials and how they could be applied to any common health problem. Trials are essential if we are to know what is effective and what is not, so ensuring we can deliver more trials is important for public health.”