Surfactant nebulization in severe COVID-19: Tracheal aspirate phospholipid turnover and metabolism.

COV-SARS-2 targets alveolar type II cells. As these cells synthesise lung surfactant, we hypothesised that surfactant dysfunction may contribute to development of ARDS in COVID-19. Here we report turnover of surfactant delivered to patients ventilated for severe COVID-19 using a novel breath-synchronized nebulizer compared with a control group. Endogenous surfactant status, turnover and half-life of administered surfactant and tracheal aspirate (TA) phospholipid metabolism were analysed by lipidomic mass spectrometry. At enrolment shortly after intubation, TA analysis (n = 20) showed markedly reduced concentrations of surfactant phospholipids, consistent with surfactant depletion. In a dose-range study in 12 ventilated COVID-19 patients with ARDS, administered surfactant resulted mean 20-fold (range 6.4 and 60.3) excess over endogenous lipid, providing proof of concept for effective nebulization, with a very rapid turnover (median half-life 7.8, range 0.4 to 20.8 h). Neither the rate of endogenous TA phosphatidylcholine (PC) synthesis nor the composition of newly synthesised PC, determined by incorporation of methyl-D9-choline, were significantly altered by exogenous surfactant nebulization. An inverse correlation between the fractional synthesis of dipalmitoyl phosphatidylcholine and inflammatory status suggested that a significant portion of endogenous TA phospholipid was derived from non-surfactant sources. This analysis is the first direct demonstration of surfactant deficiency in COVID-19; while exogenous surfactant can correct this deficiency, its rapid turnover suggests that prolonged treatment with surfactant will be needed.