A Clinical Trial of Nebulized Surfactant for the Treatment of Moderate to Severe COVID-19

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.

Inclusion criteria

• Age ≥18 years old
• Confirmed COVID-19 positive by PCR
• Within 24 hours of mechanical ventilation (ETI arm) or within 24 hours of needing either CPAP or NIV (CPAP/NIV arm)
• 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.
• Consent Declined