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

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.

The Role of Interleukin-8 in Lung Inflammation and Injury: Implications for the Management of COVID-19 and Hyperinflammatory Acute Respiratory Distress Syndrome

“…In fact, chemokines like CXCL1 (GRO α ) and IL-8 were found to be 30 times more abundant in BALF than in plasma and 200 times more abundant than IL-6 and TNF-α; consistent with the levels of these chemotactic molecules, BALF was rich in neutrophils, lymphocytes and eosinophils ( Bendib et al, 2021 ). A crucial aspect seems to be that plasma inflammatory cytokines/chemokines show limited correlations with BALF cytokines/chemokines, implying that circulating inflammatory molecules may not be a reliable proxy of the inflammation occurring in the lungs of severe COVID-19 patients ( Zaid et al, 2021 ).…”

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