Patients with Asthma and Chronic Obstructive Pulmonary Disease (COPD) have increased levels of plasma inflammatory mediators upregulated in severe COVID-19

Abstract

BackgroundRespiratory diseases such as chronic obstructive pulmonary disease (COPD) have been associated with increased risk of severe SARS-CoV-2 infection, but the mechanisms and putative immune pathways are unclear. Besides, increased levels of several immune mediators in patients with severe coronavirus disease 19 (COVID-19) have been reported.ObjectiveTo perform an immunoproteomic profiling of dysregulated plasma proteins in patients with asthma and COPD and to evaluate their relationship with biomarkers of severe COVID-19.Methods92 protein biomarkers were quantified in 315 plasma samples from adult subjects (age 40-90 years) including 118 asthmatics, 99 COPD patients and 98 healthy controls, that have been recruited in two reference pneumology clinics in Colombia before the beginning of the COVID-19 pandemic.ResultsForty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 and CCL3 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11). Functional annotation revealed their enrichment in chemokine signaling pathways related with response to viral infections. Some of these proteins were found up-regulated upon SARS-Cov-2 infection of Calu-3 cells. Also, HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE have been found increased in patients with severe COVID-19. HGF, the most significant protein in this study as well as its correlated proteins could be associated with the increased risk of severe COVID-19 in COPD patients.ConclusionsAsthma and COPD patients have altered plasma levels of proteins that have been found associated with increased risk of severe COVID-19. The reasons for sharing these profiles with this infection are unknown, but our study suggest that adult patients with asthma and COPD have a systemic dysregulation in chemokine networks that could make them more susceptible to severe COVID-19.

Common physiologic and proteomic biomarkers in pulmonary and coronary artery disease

“…Whereas a large number of such biomarkers have been separately identified for COPD [34,35] and CAD [36], studies examining potential association between such biomarkers and both COPD and CAD are sparse. Inflammatory cytokines such as Interleukin-6 (IL-6), Interleukin-8 (IL-8), Tumor necrosis factor (TNF-alpha), Monocyte chemoattractant protein 3 (MCP-3) and C-C Motif chemokine ligand 11 (CCL11) have been shown to be increased in both diseases [37][38][39], in turn supporting the hypothesis that inflammation may be a treatable target in both diseases [40,41]. In addition to inflammatory pathways, the identification of additional plasma-biomarkers that associate with both diseases, may give clues to other common pathways.…”