Background Chronic obstructive pulmonary disease (COPD) is associated with increased risk of severe COVID-19, but the mechanisms are unclear. Besides, patients with severe COVID-19 have been reported to have increased levels of several immune mediators. Methods Ninety-two proteins were quantified in 315 plasma samples from 118 asthmatics, 99 COPD patients and 98 healthy controls (age 40-90 years), who were recruited in Colombia before the COVID-19 pandemic. Protein levels were compared between each disease group and healthy controls. Significant proteins were compared to the gene signatures of SARS-CoV-2 infection reported in the “COVID-19 Drug and Gene Set Library” and with experimentally tested protein biomarkers of severe COVID-19. Results Forty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 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). These proteins are involved in chemokine signaling pathways related with response to viral infections and some, were found up-regulated upon SARS-CoV-2 experimental infection of Calu-3 cells as reported in the COVID-19 Related Gene Sets database. An increase of HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE has also been experimentally detected in patients with severe COVID-19. Conclusions COPD patients have altered levels of plasma proteins that have been reported increased in patients with severe COVID-19. Our study suggests that COPD patients have a systemic dysregulation in chemokine networks (including HGF and CXCL9) that could make them more susceptible to severe COVID-19. Also, that IL-6 levels are increased in some asthmatic patients (especially in females) and this may influence their response to COVID-19. The findings in this study depict a novel panel of inflammatory plasma proteins in COPD patients that may potentially associate with increased susceptibility to severe COVID-19 and might be useful as a biomarker signature after future experimental validation.
【저자키워드】 severe COVID-19, IL6, COPD, CXCL9, HGF, plasma proteomics, 【초록키워드】 COVID-19, SARS-CoV-2, viral infection, Biomarker, severe COVID-19, IL-6, CXCL10, RAGE, SARS-COV-2 infection, susceptibility, COVID-19 pandemic, Infection, drug, chemokines, database, viral infections, chemokine, immune, COPD, Protein, Viral, Patient, age, CXCL9, Calu-3 cell, disease, mechanism, pulmonary disease, CCL3, plasma proteins, TNF, Inflammatory, chronic obstructive pulmonary disease, calu-3 cells, IL-6 levels, chronic, obstructive pulmonary disease, mediators, dysregulation, in some, plasma protein, increased risk, healthy control, plasma samples, experimental validation, healthy controls, CXCL1, asthmatic, chemokine signaling pathways, MCP-3, CCL11, protein levels, CXCL11, CCL4, gene signature, Asthmatic patients, biomarker signature, CX3CL1, gene signatures, females, Obstructive, susceptible, controls, plasma sample, systemic inflammatory, Result, tested, involved, recruited, reported, up-regulated, driven by, Significant, quantified, “COVID-19, asthmatic patient, chemokine signaling pathway, IL-6 level, 【제목키워드】 COVID-19, pulmonary, chronic, mediator, Level, Increased,