Anti-inflammatory therapy with nebulised dornase alfa in patients with severe COVID-19 pneumonia A Randomised Clinical Trial

  1. UCL Respiratory, University College London, UK
  2. University College London Hospitals NHS Trust, London, UK
  3. Exploristics, Belfast, N. Ireland
  4. Antimicrobial Defence lab, The Francis Crick Institute, London, UK
  5. National Institute for Health Research, University College London Hospital Biomedical Research Centre, UK
  6. Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK
  7. Target to Treatment Consulting Ltd, Stevenage, UK
  8. Translation, The Francis Crick Institute, London, UK

Peer review process

Not revised: This Reviewed Preprint includes the authors’ original preprint (without revision), an eLife assessment, and public reviews.

Read more about eLife’s peer review process.


  • Reviewing Editor
    Evangelos Giamarellos-Bourboulis
    National and Kapodistrian University of Athens, Medical School, Athens, Greece
  • Senior Editor
    Jos van der Meer
    Radboud University Medical Centre, Nijmegen, Netherlands

Joint Public Review:

In this study, Porter et al report on outcomes from a small, open-label, pilot randomized clinical trial comparing dornase-alfa to the best available care in patients hospitalized with COVID-19 pneumonia. As the number of randomized participants is small, investigators describe also a contemporary cohort of controls and the study concludes about a decrease of inflammation (reflected by CRP levels) after 7 days of treatment but no other statistically significant clinical benefit.

Suggestions to the authors:
• The RCT does not follow CONSORT statement and reporting guidelines
• The authors have chosen a primary outcome that cannot be at least considered as clinically relevant or interesting. After 3 years of the pandemic with so much research, why investigate if a drug reduces CRP levels as we already have marketed drugs that provide beneficial clinical outcomes such as dexamethasone, anakinra, tocilizumab and baricitinib.
• Please provide in Methods the timeframe for the investigation of the primary endpoint
• Why day 35 was chosen for the read-out of the endpoint?
• The authors performed an RCT but in parallel chose to compare also controls. They should explain their rationale as this is not usual. I am not very enthusiastic to see mixed results like Figures 2c and 2d.
• Analysis is performed in mITT; this is a major limitation. The authors should provide at least ITT results. And they should describe in the main manuscript why they chose mITT analysis.
• It is also not usual to exclude patients from analysis because investigators just do not have serial measurements. This is lost to follow up and investigators should have pre-decided what to do with lost-to-follow-up.
• In Table 1 I would like to see all randomized patients (n=39), which is missing. There are also baseline characteristics that are missing, like which other treatments as BAT received by those patients except for dexamethasone.
• In the first paragraph of clinical outcomes, the authors refer to a cohort that is not previously introduced in the manuscript. This is confusing. And I do not understand why this analysis is performed in the context of this RCT although I understand its pilot nature.
• Propensity-score selected contemporary controls may introduce bias in favor of the primary study analysis, since controls are already adjusted for age, sex and comorbidities.
• The authors do not clearly present numerically survivors and non-survivors at day 34, even though this is one of the main secondary outcomes.
• It is unclear why another cohort (Berlin) was used to associate CRP with mortality. CRP association with mortality should (also) be performed within the current study.

  1. Howard Hughes Medical Institute
  2. Wellcome Trust
  3. Max-Planck-Gesellschaft
  4. Knut and Alice Wallenberg Foundation