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Few medical advances can top the record speed and success of COVID-19 vaccines — except perhaps the transformation of COVID-19 care.
In the spring of 2020, British doctors and nurses were desperately trying to save lives from a new deadly disease. And through no fault of their own, they were often unable to save them.
“It was oxygen and paracetamol really, that’s all we had,” said Ray Sheridan, consultant general physician at the Royal Devon & Exeter NHS Foundation Trust hospital.
“You did all the good basic medicine and nursing” to make sure patients were comfortable, supported, fed and hydrated, he explained. “And you crossed your fingers.”
But no amount of praying and hoping was enough to bring down the high fatality rates in those early weeks, particularly among older people and those with underlying health conditions. To date, over 128,000 people have now died within 28 days of a positive coronavirus test in the U.K.
Mortality rates in hospital have “plummeted” between the first and second waves of the pandemic, said Liz Lightstone, a kidney specialist at Imperial College Healthcare NHS Trust. “Even if you get COVID-19 badly enough to be admitted, you are much, much more likely to survive now than a year ago and much less likely to need treatment in intensive care,” she said.
On top of vaccines, treatments have played a huge part. These include repurposed off-the-shelf drugs as well as new medicines developed specifically in record time to treat COVID-19.
But the growing confidence of health care staff in treating COVID-19 has also helped boost the chances of survival, argues Lightstone, who co-chairs Imperial’s COVID-19 treatment and guideline group.
“It’s less scary for staff and patients now,” Lightstone said. “We know what to do, which we didn’t a year ago.”
That’s also the outlook across parts of Europe. In Germany, 30 percent of hospitalized patients were admitted to ICU during the first wave of the pandemic, compared with 14 percent in the second wave, according to a study published in the Lancet. While the ICU survival rate itself stayed roughly the same in the first and second waves (around 50 percent), the drop in ICU admission “clearly suggests a dramatic improvement in the management of patients with COVID-19,” the authors write.
‘Cup of tea medicine’
Unable to breathe and infected with a deadly disease with no known cure, patients were scared when they were hospitalized in those early days.
Staff were scared, too. Thousands of NHS staff fell sick with COVID-19, and hundreds of health care staff have died from coronavirus. Between March 9, 2020 and May 7, 2021, there were 639 deaths among health care workers involving coronavirus, according to the Office for National Statistics.
So simply providing reassurance was one of the most effective treatments for these terrified patients.
“We did what we called cup-of-tea medicine,” said Sheridan. “Giving them a cup of tea and having a chat with them really helped them to calm down.”
Importantly, this reassurance likely helped to calm them, slowing their heart rate, which in turn helped to improve their breathing.
“If you feel safer, you’re less anxious. And if you’re less anxious, you’re breathing better, even if you’ve got pneumonitis,” explained Lightstone. “Because anxiety makes you not use your oxygen properly.”
Meanwhile, clinical trials got underway early last spring to immediately start testing potential treatments. The National Institutes for Health Research funded more than 100 COVID-19 research studies, working with partners across the U.K. The largest was the RECOVERY trial, which was designed to test multiple treatments, from antibiotics to antimalarial drugs, to root out therapies that worked.
As doctors waited for news from these trials, they were also learning on the job every day.
“We worked out that if you have patients in certain positions, on what’s called proning (lying on their stomach), or you get them sitting up, they did better,” said Sheridan.
Administering oxygen through special machines usually reserved for children in emergency wards also helped, he said. High-flow nasal oxygen, with minimally invasive nasal tubes, allowed patients to receive 60 liters of oxygen a minute, or four times more than the standard mask.
“So you’ve basically given rocket fuel oxygen,” said Sheridan. “And that can be done on an ordinary ward and side room.”
It’s difficult to quantify what difference these incremental changes made to patients’ chances of surviving from coronavirus. But “once you have a confident approach to what you’re doing, and optimism that we have treatments and many more people are going to survive, [it] makes it a better patient experience,” said Lightstone.
The biggest change
Then, on June 16, 2020, doctors could finally treat patients with the first proven life-saving treatment — the cheap and readily available steroid dexamethasone.
Dexamethasone was administered to patients the same day that the RECOVERY trial released the interim results, with backing from the NHS leadership.
The challenge was that going onto steroids “was quite controversial at the time,” said Sheridan. Since these types of drugs suppress someone’s immune system, it “isn’t intuitive,” he explained. But the results have been “amazing.”
Everyone who is hospitalized in the U.K. is given the drug straight away. For Sheridan, that meant that on his ward of 25 patients, one more person would survive. And for the really sick patients in intensive care, “you only have to treat eight people to save a life,” he said. “That was the turning point.”
Familiarity also made a big difference. It was “almost instantly taken up because staff were very comfortable and knew how to use it,” said Lightstone. “This was transformative in the second wave, because people were given steroids” as soon as they were hospitalized.
In addition, steroids give people an appetite, which means patients can eat and ultimately get more energy to fight the illness, she said.
The next treatment to be rolled out, remdesivir, has been more controversial, and has yet to secure the backing of the World Health Organization. But Lightstone is more positive: “We use it routinely, and we’ve got clear guidelines on how to use it and who you can use it with, and we think it helps.”
European countries also favor the drug. After the European Medicines Agency green-lit its use in June 2020, the European Commission secured doses for EU countries in July, then placed a bigger order in October at the request of EU countries, despite the WHO position.
Then came the first monoclonal antibody therapy, tocilizumab, for severely sick hospital patients, in November.
“Tocilizumab was a big change,” said Lightstone. “We could use it in everyone who needed critical care.”
As medical staff discovered, the big advantage of both tocilizumab and sarilumab, another antibody authorized for COVID-19 treatment, is that they suppress the body’s natural reaction — inflammation — to the underlying infection. And it’s this reaction, rather than the viral infection, that can cause the most damage to lungs and other organs by the time a patient is hospitalized.
In short, they saved lives on top of the existing treatments.
Sum of the parts
Once treatments started to come on board, the next challenge was staying abreast of the clinical evidence and ensuring staff were all up to speed.
In a disease that affects multiple organs and systems, it became apparent early on that guidelines needed developing — and updating — as well as systematic assessment from multiple disciplines. Infectious disease specialists, radiologists, respiratory doctors, pharmacists, hematologists and more were involved in this process.
Treating sick COVID-19 patients is an enormous “team effort,” said Sheridan. He said he once counted 20 teams involved in the care of one very sick young woman, from midwives to obstetricians to radiologists to infection control. “We really celebrated that when this lady went home.”
In London, at Imperial, the treatment guideline has been updated 14 times so far, Lightstone noted. “And we make sure everyone knows about the changes on the door.” Given that junior doctors have now returned to a rotation system this year — in contrast to the worst times of the pandemic — “you have to keep on reminding people this is how we do it, this is our guideline.”
While hospital treatments, vaccinations, and health care teams’ confidence have significantly improved outcomes today compared with a year ago, there’s still room for more and better therapies. Those include treatments at home and for those who become severely ill and are referred to intensive care.
For non-hospitalized patients in the early stages of COVID-19, treatment options are still limited to over-the-counter drugs like paracetamol. And some EU countries and the U.S. (but not yet the U.K.) are offering intravenous antibodies to newly diagnosed patients at risk of serious illness, including therapies from Regeneron/Roche and Eli Lilly.
But more treatments are on the horizon. For example, work is underway to accelerate the development of easy-to-take pills, known as antivirals, to prevent the virus from taking hold and causing more severe illness. The U.K. has said it wants to roll out two new COVID-19 antivirals for use this fall.
For patients in need of critical care, data from the Intensive Care National Audit and Research Centre (ICNARC) suggest that there’s also a need for better treatments. In the first wave, the chances of surviving two weeks after starting critical care were 71.9 percent, compared with 76.8 percent in the second wave. However, the improvement in survival between the first and second waves becomes smaller the longer a patient stays in intensive care.
Currently, monoclonal antibodies tocilizumab and sarilumab are authorized for critical care. But researchers are also looking at other antibodies that also dampen the body’s inflammatory response, said Anthony Gordon, a consultant in intensive care medicine at St Mary’s Hospital, London. That includes novel drug candidate namilumab, and infliximab, an arthritis drug, where “there may be some benefit” even though results are preliminary, he explained.
“We’ve taken the approach that we know [tocilizumab and sarilumab] work,” so others are worth exploring, said Gordon, who is also chief investigator of the international REMAP-CAP trial investigating COVID-19 treatments for hospital patients.
A third novel monoclonal antibody, lenzilumab, has recently been submitted for approval with the Medicines and Healthcare Products Regulatory Agency, also to treat the hyper-inflammatory reaction in seriously ill COVID-19 patients.
Because these types of drugs also increase the risk of infections, only patients who aren’t responding to current therapies would likely be eligible for treatment, said Gordon.
Meanwhile, for immunosuppressed patients who are unable to mount an immune response naturally or after vaccination, Regeneron/Roche’s antibody cocktail has recently proven to be effective in hospitalized patients. The catch is that doctors can’t immediately give it to their patients: The companies didn’t carry out the trial themselves and haven’t filed for a license in this patient group, leaving it inaccessible to doctors for their patients.
Still, Sheridan is hopeful that the NHS and the U.K. regulator will find a solution, and quickly.
More broadly, the good news, according to Lightstone, is that “this is the first time that we have evidence that there’s a treatment that might work” in these patients who really need it.
This article is part of POLITICO’s premium policy service: Pro Health Care. From drug pricing, EMA, vaccines, pharma and more, our specialized journalists keep you on top of the topics driving the health care policy agenda. Email [email protected] for a complimentary trial.