Lung surfactant is present in the lungs. It covers the alveolar surface where it reduces the work of breathing and prevents the lungs from collapsing. In some respiratory diseases and in patients that require ventilation this substance does not function normally. This study will introduce surfactant to the patients lungs via the COVSurf Drug Delivery System
The hypothesis behind the proposed trial of surfactant therapy for COVID-19 infected patients
requiring ventilator support is that endogenous surfactant is dysfunctional. This could be
due to decreased concentration of surfactant phospholipid and protein, altered surfactant
phospholipid composition, surfactant protein proteolysis and/or oedema protein inhibition of
surfactant surface tension function and/or oxidative inactivation of surfactant proteins.
Variations of these dysfunctional mechanisms have been reported in a range of lung diseases,
including cystic fibrosis and severe asthma, and in child and adult patients with ARDS. Our
studies of surfactant metabolism in adult ARDS patients showed altered percentage composition
of surfactant PC, with decreased DPPC and increased surface tension-inactive unsaturated
species, and decreased concentrations of both total PC and phosphatidylglycerol (PG)
The SARS-CoV-2 virus binds to the angiotensin converting enzyme-2 (ACE2) receptor, which is
preferentially expressed in the peripheral lung ATII cells. Consequent viral infection of
ATII cells could reduce cell number and impair the capacity of the lungs to synthesise and
secrete surfactant. This, however, has not yet been demonstrated empirically in COVID-19
patients. If this is the case, then exogenous surfactant administration to the lungs is
potential one treatment option to mitigate disease severity in these patients.
Device: COVSurf Drug Delivery System
Device introduces surfactant to the patients lungs
Other: Standard of Care
Standard of care treatment for respiratory illness
Inclusion Criteria:
- Age ≥18 years old
- Confirmed COVID-19 positive by PCR
- Within 24 hours of mechanical ventilation
- Assent or professional assent obtained
Exclusion Criteria:
- Imminent expected death within 24 hours
- Specific contraindications to surfactant administration (e.g. known allergy,
pneumothorax, pulmonary haemorrhage)
- Known or suspected pregnancy
- Stage 4 severe chronic kidney disease or requiring dialysis (i.e., eGFR < 30)
- Liver failure
- Anticipated transfer to another hospital, which is not a study site within 72 hours.
- Current participation or participation in another study within the last month that in
the opinion of the investigator would prevent enrollment for safety purposes.
University Hospital Southampton NHS Foundation Trust
Southampton, Hampshire, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
Danny B Pratt
02381204989 - 3943
danny.pratt@uhs.nhs.uk
Michael P Grocott, MD, Principal Investigator
University Hospital Southampton NHS Foundation Trust