Dot Hutchinson, lead nurse at Northern Lincolnshire and Goole NHS Trust in the U.K., was one of the first nurses to research possible treatments for COVID-19 in early 2020.
Two years later, she reflected on what it was like to treat some of the first patients with the virus as she and her colleagues went into lockdown. Despite her initial fears, her work was instrumental in the fight against COVID-19.
A Dangerous Assignment
Hutchinson is part of a medical research team at Scunthorpe General Hospital, which has recruited dozens of staff and patients to trial potential treatments for the virus, test antibody levels, and investigate the effects of long COVID.
Some of these treatments included the malaria drug hydroxychloroquine, blood plasma – which contains antibodies to the coronavirus – and dexamethasone, an anti-inflammatory steroid.
“We were out on the front line from day one,” she said. “We were in full PPE, going to see the patients getting all the information that we needed to decide whether any of these new drugs were going to be applicable for them. We knew that this was something that needed to be done desperately quickly to try and help a lot of these patients, especially in the first wave.”
Hutchinson said she was “terrified” to treat her first COVID-19 patients and that she and her colleagues were “very nervous” to begin work in what became known as the Recovery Trial.
“We started the recovery trial, which was running throughout the country, which was testing all different drugs that were already on the market but were not for this specific purpose.”
“I remember walking up there [in] trepidation and this lovely lady was behind glass, there was PPE, there were people scurrying about and it just felt like this is the start of [the unknown],” she recalled. “I think sometimes we were [just as] scared as the patients because we didn’t know. I wouldn’t like to repeat those two years.”
The team quickly discovered that hydroxychloroquine and blood plasma “really didn’t have that much of an effect,” even though former U.S. President Donald Trump was raving about the potential benefits of the drug at the time.
“But dexamethasone, probably the cheaper of the drugs, actually made a big difference and hence that became standard practice, standard care. And that’s what research is all about,” she said. There were “lots and lots of highs and lows” to being a medical research nurse “but ultimately we’re looking to benefit the nation”.
The results of the study were published in the New England Journal of Medicine in 2021.
According to the study, 2,104 patients received dexamethasone and 4,321 received the usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1,110 patients (25.7%) in the usual care group died within 28 days after randomization.
The differences in mortality varied considerably according to the level of respiratory support that the patients were receiving during the trial.
In the dexamethasone group, the death rate was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%).
The Recovery project has a long history of testing the efficacy of various treatments for common viral infections, including HIV.
The group recently finished a trial on lopinavir and ritonavir, two antivirals known to curb HIV. They looked at 1,596 patients who received the combination of the drugs and 3,376 patients who received only standard care. In a press release, the team announced there had been no significant difference in the death rate between the two groups.
“This could have worked. And it was a bust,” says Eric Topol, director of the Scripps Research Translational Institute. “It was really important to clarify that.”
The Missing Link
Large, randomized trials have been rare throughout the pandemic, even though they give providers insight into whether certain drugs are effective against COVID-19.
For example, millions of COVID-19 patients in the U.S. have received blood plasma treatments, but not alongside a control population receiving a placebo.
“We’ll know what happened to those patients, but we won’t know whether they would have been better off actually, if they hadn’t got the convalescent plasma. Partly it is about convincing clinicians that there is still an open question,” says Ana Maria Henao Restrepo, a medical officer at the World Health Organization’s (WHO’s) Emergencies Programme. “I have talked to about 2,000 clinicians all over the world in the process of establishing Solidarity, and some of them are convinced they know which drugs work.”
The U.K. has found success with these trials largely thanks to funding and support from the National Health Service, which has involved over 176 hospitals.
With a fragmented healthcare system, the U.S. has been much slower to conduct these trials by comparison.
For example, the National Institutes of Health has only completed one trial so far, a review of Gilead Sciences’s antiviral compound remdesivir that showed patients who received the drug recovered faster from COVID-19 than those that received normal care.
Considering the U.S. has the highest number of COVID-19 cases in the world, the country’s lack of results has been “surprising and a bit disappointing,” says John-Arne Røttingen, who heads the steering committee of Solidarity, a program from the WHO that’s designed to evaluate repurposed drugs as possible COVID-19 therapies.