• Mathieu Blot, Marine Jacquier, Ludwig-Serge Aho Glele, Guillaume Beltramo, Maxime Nguyen, Philippe Bonniaud, Sebastien Prin, Pascal Andreu, Belaid Bouhemad, Jean-Baptiste Bour, Christine Binquet, Lionel Piroth, Jean-Paul Pais de Barros, David Masson, QuenotJean-PierreJPINSERM, LNC UMR 1231, FCS Bourgogne-Franche Comté, LipSTIC LabEx, F-21000, Dijon, France.INSERM, CIC1432, Clinical Epidemiology unit; Dijon Bourgogne University Hospital, Clinical Investigation Center, Clinical Epidemiology/Clinical tri, Pierre-Emmanuel Charles, and Pneumochondrie study group.
• Infectious Diseases Department, Dijon Bourgogne University Hospital, Dijon, France. mathieu.blot@chu-dijon.fr.
• Crit Care. 2020 Nov 2; 24 (1): 632632.

BackgroundCOVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19).MethodsBronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared.ResultsCOVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL-10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1β concentrations.ConclusionCXCL10 could be one key mediator involved in the dysregulated immune response. It should be evaluated as a candidate biomarker that may predict the duration of MV in COVID-19 ARDS patients. Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach.Trial RegistrationClinicalTrials.gov, NCT03955887.

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