Persistent alveolar inflammatory response in critically ill patients with COVID-19 is associated with mortality

IntroductionPatients with COVID-19-related acute respiratory distress syndrome (ARDS) show limited systemic hyperinflammation, but immunomodulatory treatments are effective. Little is known about the inflammatory response in the lungs and if this could be targeted using high-dose steroids (HDS). We...

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Published in:Thorax Vol. 78; no. 9; pp. 912 - 921
Main Authors: de Brabander, Justin, Boers, Leonoor S, Kullberg, Robert F J, Zhang, Shiqi, Nossent, Esther J, Heunks, Leo M A, Vlaar, Alexander P J, Bonta, Peter I, Schultz, Marcus J, van der Poll, Tom, Duitman, JanWillem, Nossent, E J, Duitman, J W, Saris, A, de Vries, H, Meijboom, L J, Bos, L D J, Reijnders, T D Y, Bontkes, H, Vlaar, A P J, Wiersinga, W J, Lutter, R, van der Poll, T, Bogaard, H J, Heunks, L, Algera, A G, Baarle, F, Beudel, M, Bomers, M, Bonta, P, Bos, L D, Botta, M, de Brabander, J, de Bree, G, de Bruin, S, Bugiani, M, Bulle, E, Buis, D T P, Chouchane, O, Cloherty, A, Dijkstra, M, Dongelmans, D A, Dujardin, R W G, Elbers, P, Fleuren, L, Geerlings, S, Geijtenbeek, T, Girbes, A, Goorhuis, B, Harris, V, Hemke, R, Hermans, S M, Horn, J, de Jong, M D, Koning, R, Lim, E H T, van Mourik, N, Nellen, J, Paulus, F, Peters, E, Pina-Fuentes, D A I, Preckel, B, Prins, J M, Raasveld, J, Reijnders, T, J de Rotte, M C F, Schinkel, M, Schultz, M J, Schrauwen, F A P, Schuurman, A, Schuurmans, J, Sigaloff, K, Slim, M A, Smeele, P, Smit, M, Stijnis, C S, Stilma, W, Teunissen, C, Thoral, P, Tsonas, A M, Tuinman, P R, van der Valk, M, Volleman, C, van Vugt, M, Wouters, D, Zwinderman, A H, Brouwer, M C, van de Beek, D, de Beer, F M, Claushuis, T A, Glas, G J, Hoogendijk, A J, van Hooijdonk, R T, Huson, M A, Juffermans, N P, Scicluna, B, Schouten, L R, van der Sluijs, K F, Wiewel, M A, Witteveen, E
Format: Journal Article
Language:English
Published: England BMJ Publishing Group Ltd and British Thoracic Society 01.09.2023
BMJ Publishing Group LTD
Subjects:
ARDS
Biomarkers
Body mass index
Bronchoscopy
Coronaviruses
COVID-19
critical care
Drug dosages
Hypotheses
innate immunity
Intubation
Laboratories
Mortality
Patients
Plasma
Proteins
Respiratory distress syndrome
Respiratory failure
Respiratory infection
Steroids
Ventilators
United States > US
California
COVID-19
critical care
innate immunity
ARDS
respiratory infection
bronchoscopy
ISSN:0040-6376, 1468-3296, 1468-3296
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Summary:IntroductionPatients with COVID-19-related acute respiratory distress syndrome (ARDS) show limited systemic hyperinflammation, but immunomodulatory treatments are effective. Little is known about the inflammatory response in the lungs and if this could be targeted using high-dose steroids (HDS). We aimed to characterise the alveolar immune response in patients with COVID-19-related ARDS, to determine its association with mortality, and to explore the association between HDS treatment and the alveolar immune response.MethodsIn this observational cohort study, a comprehensive panel of 63 biomarkers was measured in repeated bronchoalveolar lavage (BAL) fluid and plasma samples of patients with COVID-19 ARDS. Differences in alveolar–plasma concentrations were determined to characterise the alveolar inflammatory response. Joint modelling was performed to assess the longitudinal changes in alveolar biomarker concentrations, and the association between changes in alveolar biomarker concentrations and mortality. Changes in alveolar biomarker concentrations were compared between HDS-treated and matched untreated patients.Results284 BAL fluid and paired plasma samples of 154 patients with COVID-19 were analysed. 13 biomarkers indicative of innate immune activation showed alveolar rather than systemic inflammation. A longitudinal increase in the alveolar concentration of several innate immune markers, including CC motif ligand (CCL)20 and CXC motif ligand (CXCL)1, was associated with increased mortality. Treatment with HDS was associated with a subsequent decrease in alveolar CCL20 and CXCL1 levels.ConclusionsPatients with COVID-19-related ARDS showed an alveolar inflammatory state related to the innate host response, which was associated with a higher mortality. HDS treatment was associated with decreasing alveolar concentrations of CCL20 and CXCL1.
Bibliography:Original research
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ISSN:0040-6376
1468-3296
1468-3296
DOI:10.1136/thorax-2023-219989