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Chemokines and eicosanoids fuel the hyperinflammation within the lungs of patients with severe COVID-19

Chemokines and eicosanoids fuel the hyperinflammation within the lungs of patients with severe COVID-19

Authors :
Michel Laviolette
Isabelle Dubuc
Younes Zaid
Nicolas Flamand
Louis Flamand
Olivier Flamand
Anne Sophie Archambault
Étienne Doré
Eric Boilard
Source :
The Journal of Allergy and Clinical Immunology
Publication Year :
2021
Publisher :
Elsevier BV, 2021.

Abstract

Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection can lead to a variety of clinical outcomes ranging from the absence of symptoms to severe acute respiratory disease and ultimately death. A feature of patients with severe Coronavirus disease 19 (COVID-19) is the abundance of inflammatory cytokines in the blood. Elevated levels of cytokine are predictive of infection severity and clinical outcome. In contrast, studies aimed at defining the driving forces behind the inflammation in lungs of severed COVID-19 subjects remain scarce. Objective To analyze and compare the plasma and bronchoalveolar lavages (BALs) of patients with severe COVID-19 (n=45) for the presence of cytokines and lipid mediators of inflammation (LMI). Methods Cytokines were measured using Luminex multiplex assay and LMI measured using LC-MS/MS. Results We reveal high concentrations of numerous cytokines/chemokines/LMI in BALs of patients with severe COVID-19. Among the 13 most abundant mediators in BALs, 11 were chemokines with CXCL1 and CXCL8 being 200 times more abundant than IL-6 and TNF-α. Eicosanoids were also elevated in lungs of severe COVID-19 subjects. Consistent with the presence chemotactic molecules, BALs were enriched for neutrophils, lymphocytes and eosinophils. Inflammatory cytokines/LMI in plasma showed limited correlations with those present in BALs, arguing that circulating inflammatory molecules may not be a reliable proxy of the inflammation occurring in the lungs of severe COVID-19 patients. Conclusions Our findings indicate that lungs hyperinflammation of severe COVID-19 patients is fueled by excessive production of chemokines and eicosanoids. Therapeutic strategies to dampen inflammation in COVID-19 patients should be tailored accordingly.<br />Graphical abstract

Details

ISSN :
00916749
Volume :
148
Database :
OpenAIRE
Journal :
Journal of Allergy and Clinical Immunology
Accession number :
edsair.doi.dedup.....3a8ca295de8f943a62c858c8374b9189
Full Text :
https://doi.org/10.1016/j.jaci.2021.05.032