University College London and The Francis Crick Institute collaborate to test cystic fibrosis drug in hospitalised COVID-19 patients

Research title

Investigation of an approved nebulised human Dornase enzyme (Pulmozyme) to reduce hyperinflammation in hospitalised people with COVID-19 (The COVASE study)

Summary

University College London in collaboration with The Francis Crick Institute, with funding from LifeArc, is set to investigate an approved nebulised recombinant human deoxyribonuclease I (Dornase alfa) as a treatment for COVID-19. The COVASE trial aims to use Dornase alfa to reduce hyperinflammation in hospitalised participants with COVID-19.

Research organisation

University College London and The Francis Crick Institute

Researchers

Principal Investigator:

  • Dr Joanna Porter, University College London Hospitals

Co-investigators:

  • Venizelos Papayannopoulos,The Francis Crick Institute
  • Veronique Birault, The Francis Crick Institute

Potential of repurposed therapeutic for COVID-19 pandemic

It is thought that the symptoms of severe COVID-19 are caused by an overactivation of the body’s own immune response trying to kill the virus. This hyperinflammation triggered by the infection can also lead to damage of the lungs and potentially other organs and, in very severe, late-stage disease, kill patients.

During a viral infection, an important cell type of the body’s innate immune response called neutrophils releases neutrophil extracellular traps (NETs) which aim to capture the virus and alert the immune system of its presence. However, excessive production of NETs can cause issues such as hyperinflammation.

A drug called pulmozyme cuts up NETs to reduce their unwanted effects. Pulmozyme has been used in people with cystic fibrosis (CF) since 1994 and therefore has good safety data. It is given directly to the lungs by a nebuliser and has been shown to help people with CF to breathe by cutting up the NETs that accumulate in their lungs, reducing inflammation and infections. The Francis Crick Institute is concurrently completing research on how NETs induce pro-inflammatory cytokines, which play a large role in the inflammatory response seen in COVID-19. Therefore, researchers believe pulmozyme could have a beneficial effect in people with COVID-19, resulting in improved clinical outcome and earlier discharge from hospital.

With funding from LifeArc, 40 patients diagnosed with COVID-19 who are admitted to University College London Hospitals NHS Trust and at risk of ventilatory failure will be recruited into the COVASE study. Up to an additional ten subjects may be added after the sample size re-estimation. Over seven days of treatment with pulmozyme, the effect on NETs, inflammation and clinical course will be closely monitored. Primarily, C-reactive protein, a biomarker that is already routinely used to assess the level of inflammation in COVID-19 patients, will be measured to assess the effect of nebulised pulmozyme on the inflammatory and immune response.

If the trial shows positive results, the potential uses for the treatment could extend beyond hospitalised patients, as Pulmozyme can be self-administered at home. Therefore, it could provide benefit in subjects with COVID-19 who have mild disease and are self-isolating, and in those discharged from hospital to recuperate at home.