Dr. John Wright of Bradford Royal Infirmary (BRI) describes some of the ongoing trials to find a cure for Covid-19 and suggests that a combination of three different types of drugs may hold the key.
At BRI, we are now participating in eight different clinical trials to try to find a cure for Covid-19.
We are part of a huge international effort. It seems that all the light of world science has been concentrated in a laser beam directed against this almost invisible virus.
The largest of the trials we participate in is the recovery trial. More than 10,000 patients have already been recruited across the country and are taking either a placebo or one of the many other drugs. (I wrote about this important lawsuit last month.)
Last week at BRI we recruited the first patient in the UK for a small trial to test whether a new drug made by AstraZeneca is safe and effective. It is one of several small trials – jointly known as the Accord trial – designed to test other drugs that could be added to the Recovery trial.
The hope is that this drug AstraZeneca, which does not yet have a name, will help mitigate an excessive and dangerous reaction of the immune system which occurs in a small proportion of patients, causing body shock and shutting down vital organs, such than the lungs, heart, blood vessels and kidneys.
This overreaction has been called a “cytokine storm” – cytokines being molecules that signal the presence of an infection that the body must fight. The drug in the new trial blocks a cytokine called IL-33 (or interleukin-33).
Mark Winterbourne, who volunteered to take the IL-blocker, arrived at the hospital with symptoms that were initially due to gallstones. It wasn’t until after he tested positive for Covid-19 that we realized that this was the likely source of the problem. (Covid-19 is a disease with a wide variety of symptoms – but it is an unusual case!) Mark says that volunteering comes naturally to him; while working as a volunteer photographer for the Great North Run, he met and became friends with Sir Mo Farah.
I suspect that a vaccine for Covid-19 is still a year away, so these treatment-seeking trials are essential.
Doctors here anticipate a time – not too far, they hope – when anyone with early symptoms can drive to a test center, get a tampon, get a quick result and get a prescription for a combination of drugs effective, before the worst of their symptoms sets in.
This combination may include an antiviral drug, an immunosuppressive drug, and an anti-inflammatory drug.
Among the antivirals tested, one may help prevent the coronavirus from attaching to the lining of the lungs, and another may help prevent it from reproducing in the body.
Immunosuppressive drugs may help prevent an excessive immune response to the virus – the cytokine storm. If the IL-33 blocker in the Accord trial is effective, it would be a competitor.
Anti-inflammatory drugs include steroids – for example dexamethasone, one of the first drugs included in the recovery test.
Professor John Wright, doctor and epidemiologist, is the head of the Bradford Institute for Health Research and a veteran of the cholera, HIV and Ebola epidemics in sub-Saharan Africa. He writes this newspaper for BBC News and records from hospital rooms for BBC Radio.
- Listen to the next episode of The NHS Front Line on BBC Sounds or the BBC World Service
- Or read the previous online journal: A patient with hours to live who proved everyone was wrong
It seems increasingly unlikely that a single drug will cure Covid-19. It is through drug combinations that in the past we have overcome tuberculosis – with a combination of antibiotics – and HIV – with a combination of antiretrovirals – and I expect that to be also the way we fight this disease.
BRI respiratory consultant Dinesh Saralaya is optimistic that combination therapy will be available before the end of the summer.
“I think we will find at least two or three drugs that will prevent these patients from having to be hospitalized,” he said.
“You will go to the test center and you will receive the drugs once you have been diagnosed. According to current strategies, you catch the Covid virus, you isolate yourself, then you get worse, you get a temperature, you start to run out of breath, then you enter. But people have to get the drugs very early. “
Another of our consultants potentially contributes to another trial – as an antibody donor.
Debbie Horner caught Covid-19 at a very early stage of the epidemic and recovered quickly. Two weeks ago, when a call was made for people like her to donate convalescent blood plasma, she immediately agreed.
Researchers are concerned with whether antibody-rich plasma from people who have had Covid-19 will help other patients fight the disease. This work is also part of the recovery test.
It has now been discovered that the patients most likely to have high levels of antibodies are men over the age of 35 who have fallen so ill that they have to be hospitalized. The NHS Blood and Transplant (NHSBT) wants to recruit donors who have recovered from Covid-19 and who are either male, over 35 years old, or sick enough to be hospitalized.
Debbie had a mild case, so her plasma may not be as rich in antibodies as the team would like. The results are not yet known. If her plasma is wanted, she will gladly do more.
“It’s a little different from taking blood normally,” she says. “They take out a fraction of the blood – the plasma fraction – and then they give you back all of your red blood cells and other pieces of blood that aren’t needed, so basically it’s like getting a little dehydrated. “
A few cups of tea is enough to solve this problem, says Debbie.
Mike Murphy, professor of transfusion medicine at the University of Oxford, says this is a great opportunity to better understand the value of plasma transfusions in general. Plasma was collected in the late 2000s to see if it would be a way to treat people with Ebola and the flu, he said.
“But by the time there were enough convalescent donors who had recovered from the infection and were able to donate, the peak of infection had passed, so there was no way to test the benefits of convalescent plasma. The Covid-19 pandemic is obviously different. “