RECOVERY: the game-changing Covid-19 treatment trial that saved lives

In March 2020, Bryan White was admitted to hospital in Leicester with Covid-19, seriously unwell and fearing for his life. “I was admitted on the Sunday... and basically told, 'if you don’t improve by next Friday, you’ll be in intensive care’,” he recalled.

But his condition improved dramatically – enough for him to go home sooner than anyone expected. The reason became clear in the months that followed. During his stay, Bryan agreed to take part in the RECOVERY trial and was assigned to treatment with dexamethasone. 

“That’s the only reason I’m probably here now,” he said. “[It was] obviously the drug – but we didn’t know that at the time.” 

At the start of the pandemic, nobody knew how Covid-19 worked, or how the most seriously ill patients would respond to potential treatments. But thanks to evidence from RECOVERY, Bryan’s story would be repeated about a million times around the world.

The early days of the pandemic were defined by fear and uncertainty as hospitals were quickly overwhelmed. “It was horrendous. It was like being in a war,” recalled Maheshi Ramasamy, infectious disease consultant at Oxford University Hospitals NHS Foundation Trust.

The mechanisms of this new viral infection – and the body’s response to them – were simply not understood. Some patients would deteriorate rapidly, developing severe breathing problems requiring oxygen or intensive care. It was impossible to know which treatments would work and when they could be given safely.

With no reliable evidence, clinicians felt powerless to help patients who became severely unwell. 

“Normally, as a clinician, if somebody comes in with a disease and you don’t know what to do, you can phone a colleague, look it up – there are resources you can access,” explained Maheshi. “But here, nobody knew what to do and the hospital couldn’t cope. We didn’t have the oxygen supply to manage all these people.”

As clinicians worked on the frontlines, University of Oxford professors Martin Landray and Peter Horby were devising a systemised way to understand which existing drugs might be effective in treating severe cases of Covid-19. Their collaboration was initiated through Wellcome, combining Martin's expertise in large-scale clinical trials and Peter's expertise in emerging infectious diseases. 

They knew the traditional clinical trial model would be no match for the speed and scale of the viral infection. As Martin explained, this trial needed to be pragmatic and “right for pandemic conditions”. Getting up and running quickly and safely would require close collaboration between researchers, data scientists, funders, regulators, health bodies and medical teams on the ground.

Partnering with two experienced clinical trial units in Oxford, the team quickly secured ethical and regulatory approvals. Data specialists and programmers helped to develop the randomisation system and data capture tools they’d need to collect robust evidence on a large scale.

The Randomised Evaluation of Covid-19 Therapy (RECOVERY) trial began by studying a small number of drugs, all at the same time. As results came in, treatments that didn’t work were dropped from the trial and new options were added. This allowed the trial to adapt quickly and focus on the most promising options.

Thanks to the partnership with the NHS and the number of people enrolled, RECOVERY was able to generate reliable evidence in a short time, which was crucial. And the streamlined trial design paid off. “Within about nine days of drafting the protocol, we walked across the road to the John Radcliffe Hospital and the first patient was enrolled,” explains Peter. Maheshi was the doctor who enrolled this patient. 

“At that stage of the pandemic, it was clear that even if vaccines were developed quickly, they would take time to reach people around the world,” says Nick Cammack, Head of Product Development Partnerships at Wellcome. “That made it essential to identify accessible, effective treatments that could save lives immediately,” he says. 

By June, it was official – robust evidence from the trial showed dexamethasone was highly effective in treating patients with severe Covid-19. The evidence showed that the drug:

• Cut the risk of death by one third for patients on ventilators 
• Reduced deaths by almost one fifth for those on oxygen only

It was a breakthrough moment in the pandemic. “That was really incredible as a medic,” explains Maheshi. “Having felt so helpless at the start of the pandemic, here was something that tangibly saved lives.”

Better still, this highly effective drug was, in Peter’s words, “simple, cheap, and already widely available”.

The RECOVERY trial findings were rapidly implemented across the NHS and global clinical practice. Ben Morton, an intensive care clinician based in Malawi during the pandemic, saw the impact of the trial findings firsthand. “It felt empowering to have something to fight Covid-19 with,” he said. “People saw dexamethasone and thought yes, we can do that. We already have it.”

Backed by funders including Wellcome, the international expansion of RECOVERY launched in February 2021, evaluating treatments suitable for diverse low- and middle-income healthcare settings.

Working with a wide range of global partners, Wellcome continued to support advances in Covid-19 treatments, helping extend the reach of RECOVERY across Asia and Africa. In 2023, the trial broadened its scope further to test treatments for other types of pneumonia, including influenza and non-viral, community-acquired pneumonia.

“Expanding RECOVERY internationally was crucial to ensure the evidence reflects patients around the world,” said Nick Cammack. “Building a diverse global evidence base helps ensure treatments are effective and practical in the settings where they’re most needed.”

The evidence from the RECOVERY trial is estimated to have saved around 1 million lives globally.

RECOVERY is regarded by some as a model for how to run clinical trials during health emergencies and target other widespread medical issues, such as heart disease.

“One of the things [RECOVERY] did was show trials don’t have to be done the way they’ve always been done,” said Martin Landray. “Any additional work or delays would have cost time and lives.”

“The simplicity of RECOVERY could carry into trials going forward. There are signs of progress in various places ... the MHRA has done a fantastic job speeding up their approvals timelines, the ethics committees likewise.”

The trial is a reminder of the importance of scientific collaboration, public engagement and rigorous evidence in the face of health crises.

It also shows the power of sharing trial results quickly and publicly – something that’s left a lasting legacy, according to Maheshi: “I think it’s had a real knock-on effect for engaging people with research more generally. They see the impact that research has on their lives.”

This rings true for Bryan. Reflecting on his experience, he said: “Without trials and tests, science wouldn’t move forward. As long as I live, I’ll be happy to volunteer.”

The RECOVERY trial was established and funded by UK Research and Innovation (UKRI) and the National Institute for Health and Care Research (NIHR). Its international expansion, launched in 2021, has been supported by a wider group of global funders, including Wellcome, the Gates Foundation, the UK Foreign, Commonwealth & Development Office, Health Data Research UK, and the Medical Research Council, alongside international research partnerships.