A collaboration between the Antimicrobial Defence Laboratory, led by Venizelos Papayannopoulos, and Joanna Porter, Professor of Respiratory Medicine at UCL and Consultant at UCLH, has found that a drug commonly used to treat cystic fibrosis improved outcomes for patients with severe COVID-19 pneumonia. This drug could be used to treat other respiratory infections in the future. 

The study, published in eLife, found that the drug dornase alfa reduced hyper-inflammation in COVID-19 pneumonia patients, which occurs when the body’s immune system reacts too strongly and can lead to tissue damage and death.

Since the beginning of the COVID-19 pandemic, the number of SARS-CoV-2 infections that result in death has fallen dramatically, from a high of almost 1,400 deaths on 19 January 2021 to 143 deaths on 21 June 2024. This is partly down to increased immunity from prior infection or vaccination, as well as improved treatments for those who become seriously ill, such as dexamethasone, a steroid that helps to tackle the hyper-inflammation that was a key factor in many COVID-19 deaths.

In this study, the team set out to assess whether dornase alfa could be used to improve outcomes for patients admitted to hospital with severe COVID-19 pneumonia who required oxygen. 

Out of a total of 39 participants, 30 were randomised to receive twice-daily treatment with nebulised dornase alfa in addition to best available care (BAC) which included dexamethasone, with nine patients randomised to BAC only.

Patients treated with dornase alfa had a 33% reduction in systemic inflammation on top of the reduction provided by dexamethasone, as measured by C-reactive protein (CRP) levels in the blood over seven days or until they were discharged from hospital. 

Venizelos Papayannopoulos said: 

Dexamethasone has been highly successful in treating patients with severe COVID-19 pneumonia and is now standard care in the UK. But it isn’t suitable for some patients, such as those with diabetes, those that do not require oxygen, and in very severe cases it may not be enough. Dornase alfa can be used to treat a wider variety of patients and gets right to the heart of the inflammatory response. Based on these results, we think it will be a valuable cost-effective tool for tackling severe COVID-19 illness.

Patients treated with dornase alfa were also more likely to need less oxygen and be discharged sooner compared to patients who received BAC. These additional benefits could help to free up beds and resources in the UK’s busy hospitals.

The next step will be to conduct larger clinical trials to ensure dornase alfa is safe and effective for treating severe COVID-19 pneumonia. There is also potential for the drug to be trialled for other respiratory infections and conditions, such as acute exacerbations of pulmonary fibrosis, where inflammation of already scarred lung tissue affects how well oxygen can be absorbed.

Joanna Porter said: 

Given that we observed a significant further reduction in C-reactive protein in patients who were already receiving dexamethasone, which also reduces inflammation, this trial is proof-of-concept that dornase alfa can be used to treat severe COVID-19 pneumonia. If we can help patients recover more quickly and get home sooner, this would be great for them and also help to reduce pressure on the NHS.

I’m optimistic that dornase alfa will have applications for treating other respiratory infections, and acute exacerbations of other chronic lung diseases, such as pulmonary fibrosis, that may share mechanisms with severe COVID-19.

Catriona Crombie, Associate Director of Technology Transfer and Philanthropic Fund at LifeArc, said: 

We were delighted to support this study that has demonstrated how repurposing of a treatment commonly used for cystic fibrosis can be effective in improving outcomes for patients with severe COVID-19. LifeArc is committed to helping take scientific ideas out of the lab and into medical breakthroughs for patients, especially where there is an unmet medical need. To date, we have provided more than £27 million to fund the search for new medicines and diagnostics to address Covid-19.