Working to understand treatments for COVID-19

Published: 18 August 2020

Doctors treating coronavirus patients are presented with a variety of options for how best to treat their patients. But with much of the data coming from small case reports or emerging clinical trials results, it can be difficult to know the best options to take.

However, a new review article, written by St George’s researchers and published in Frontiers in Immunology this week, takes a great step towards providing more clarity on the treatments doctors have to hand, and the emerging drugs that may help to tackle COVID-19 on the frontline.

Treatment options include drugs that affect the immune response

The review explains that there are lots of different treatments available for the management of coronavirus when they present with infection at hospital, many of which impact the immune response. These include immunomodulator therapies that suppress small molecules called cytokines that are released in the body as a response to inflammation.

One such therapy is tocilizumab, which blocks a cytokine called IL-6. Professor of Rheumatology at St George’s, Nidhi Sofat (pictured below), is the senior author on the paper and had used the drug to treat other inflammatory conditions before.

“Tocilizumab is used for rheumatoid arthritis and other rare fever syndrome conditions,” she says.

“In the Trust, we have a compassionate use scheme for certain patients to use tocilizumab. Part of the review paper describes our experience of managing one patient with coronavirus and the positive outcome they had.

“The tocilizumab was able to suppress the inflammatory response very quickly and she has continued to do very well after having been discharged.”

Trials of tocilizumab for treating Covid-19 are currently underway, including academic and pharmaceutical company trials.

Seeing a successful outcome for this patient sparked Professor Sofat’s interest in how treatments she was using every day in clinic could potentially be repurposed as novel COVID-19 therapies.

One example that has already been shown to have had success for treating patients is dexamethasone. The drug has been shown to save lives in the national RECOVERY trial, which is being led by the University of Oxford, and includes St George’s researchers coordinating the trial in Tooting.

Professor Sofat is now coordinating another trial at the Hospital, testing a biological therapy (one that targets the immune system) called baricitinib, which is used for patients with rheumatoid arthritis.

Could an oral drug be the next answer in preventing admissions to intensive care?

Baricitinib is another cytokine inhibitor, but unlike some drugs, including tocilizumab, it has the potential to block all the main cytokine pathways, rather than just one. It can also be easily administered as an oral medication.

When it comes to treating coronavirus, baricitinib has been shown to have early promise in Italy in a small series of cases. A new clinical trial has recently opened, testing the drug in coronavirus patients.

Funded by the pharmaceutical company Eli-Lilly and coordinated by Professor Sofat in the UK, the trial hopes to recruit 400 people worldwide to assess the effectiveness of the therapy on disease progression in patients with COVID-19.

Professor Sofat adds, “The outcome measures we’re looking at are the prevention of admission of patients into intensive care units and the time they spend in hospital. Both are really important for patients and their survival, and it would be great if we could see improvements in these.”

As well as a clinical trial, baricitinib is also being tested in academic studies to analyse the mechanisms of how it might work. This type of work is important to understand not just for drugs being used to treat coronavirus, but also for people being treated for other long-term conditions who have the potential to catch the disease.

Are people on long-term medication at greater risk?

There is a considerable number of patients who have long-term conditions that require treatment on a daily basis. These can include patients with inflammatory disorders such as rheumatoid arthritis who require immunomodulator treatments that affect the immune system.

Doctors and patients don’t yet understand how these drugs may affect a person’s response or susceptibility to COVID-19.

“When the pandemic started, there were recommendations put out by various societies because there were concerns patients on immunomodulators may potentially have a higher risk of getting COVID-19,” says Professor Sofat.

With this in mind, an amendment has been made to Professor Sofat’s long-term study into patients with arthritis.   

“We were interested to know how the rate of coronavirus in a real-world population of these patients compares to people without inflammatory conditions, as well as understanding how their disease progresses,” she says.

While patients in the study were previously only tracking symptoms related to arthritis, those that are diagnosed with coronavirus will now have further questions around symptoms related to the infection. They will also be offered a blood test to understand how their immune system may have responded to the disease.

Professor Sofat adds, “Hopefully the data from this will help us to inform and advise our clinical practice for future spikes.

“A lot of patients at the start of the pandemic were asking if they should stop taking their drugs because they were fearful of developing coronavirus, but this data will help inform them. If we find that immunomodulators do not lead to a higher risk of developing COVID-19 infection that will be very reassuring for patients.”

Throughout the pandemic and beyond, collaboration is key

No single trial or single researcher will have all the answers to the coronavirus pandemic. Tackling the virus requires a multi-pronged approach, covering prevention, testing and treatment.

As well as testing new treatments, St George’s is also playing a role in developing vaccines to protect people from the virus and designing tests that can easily detect current or previous infections. But arguably, the most effective work will be done through collaborations across these areas.

“Because we’re on both the NHS Trust and University site, working on coronavirus has been a really positive experience,” says Professor Sofat. “We’ve all found that people have come together in ways they weren’t necessarily before.

“I’m working with various teams and people, including Professor Sanjeev Krishna on understanding the immune response and Professor Emma Baker on compassionate drug use. We’re taking a much more combined effort, which we didn’t have before the pandemic.”

This combined effort is already proving it’s worth, with St George’s demonstrating itself as one of the most active research facilities in the country for tackling coronavirus.

In order to accelerate discoveries, the University has launched a Coronavirus Action Fund to raise money for vital research into the pandemic and is actively seeking support for a broad research programme involving all parts of the University.  

While the pandemic continues, more work still needs to be done. But with focused research and collaborative efforts, the University will continue to make progress in preventing, detecting and treating the virus.