Surfactant nebulization in severe COVID-19: tracheal aspirate phospholipid turnover and metabolism
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-D
9-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.
Administration, Inhalation, Adult, Aged, COVID-19 Drug Treatment, COVID-19/metabolism, Female, Humans, Male, Middle Aged, Nebulizers and Vaporizers, Phosphatidylcholines/metabolism, Phospholipids/metabolism, Pulmonary Surfactants/administration & dosage, SARS-CoV-2, Trachea/metabolism, Acute respiratory distress syndrome, Metabolism, COVID-19, Surfactant phospholipid, Turnover
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Fink, James
56085c50-313c-4eb1-9cd7-6fd1f269ffba
Koster, Grielof
e404c38a-6f48-430a-adf0-5208228cb9e7
Panchal, Madhuriben
ad071572-6895-48e7-a3d0-5cf07cff9987
Matthews, Lewis
81327a4c-b2a8-44f9-b5b2-fc04f856a930
Berry, Lee
fa1ed75a-ee81-4aca-b302-16481e04122e
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Brealey, David
a4d31ccc-4510-43eb-8ade-556abdb5270c
Grocott, Michael P.W.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751
20 February 2026
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Fink, James
56085c50-313c-4eb1-9cd7-6fd1f269ffba
Koster, Grielof
e404c38a-6f48-430a-adf0-5208228cb9e7
Panchal, Madhuriben
ad071572-6895-48e7-a3d0-5cf07cff9987
Matthews, Lewis
81327a4c-b2a8-44f9-b5b2-fc04f856a930
Berry, Lee
fa1ed75a-ee81-4aca-b302-16481e04122e
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Brealey, David
a4d31ccc-4510-43eb-8ade-556abdb5270c
Grocott, Michael P.W.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751
Postle, Anthony D., Clark, Howard W., Fink, James, Madsen, Jens, Koster, Grielof, Panchal, Madhuriben, Matthews, Lewis, Berry, Lee, Djukanovic, Ratko, Brealey, David, Grocott, Michael P.W. and Dushianthan, Ahilanandan
(2026)
Surfactant nebulization in severe COVID-19: tracheal aspirate phospholipid turnover and metabolism.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1871 (3), [159731].
(doi:10.1016/j.bbalip.2026.159731).
Abstract
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-D
9-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.
Text
1-s2.0-S138819812600017X-main
- Version of Record
More information
Accepted/In Press date: 6 February 2026
e-pub ahead of print date: 10 February 2026
Published date: 20 February 2026
Keywords:
Administration, Inhalation, Adult, Aged, COVID-19 Drug Treatment, COVID-19/metabolism, Female, Humans, Male, Middle Aged, Nebulizers and Vaporizers, Phosphatidylcholines/metabolism, Phospholipids/metabolism, Pulmonary Surfactants/administration & dosage, SARS-CoV-2, Trachea/metabolism, Acute respiratory distress syndrome, Metabolism, COVID-19, Surfactant phospholipid, Turnover
Identifiers
Local EPrints ID: 511504
URI: http://eprints.soton.ac.uk/id/eprint/511504
ISSN: 1388-1981
PURE UUID: 1ced25c9-a10f-46b7-ae79-a2e8e1b21fca
Catalogue record
Date deposited: 18 May 2026 16:43
Last modified: 19 May 2026 01:55
Export record
Altmetrics
Contributors
Author:
Howard W. Clark
Author:
James Fink
Author:
Jens Madsen
Author:
Grielof Koster
Author:
Madhuriben Panchal
Author:
Lewis Matthews
Author:
Lee Berry
Author:
David Brealey
Author:
Ahilanandan Dushianthan
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics