Overproduction of inflammatory cytokines is a keystone event in COVID-19 pathogenesis; TNF and its receptors (TNFR1 and TNFR2) are critical pro-inflammatory molecules. ADAM17 releases the soluble (sol) forms of TNF, TNFR1, and TNFR2. This study evaluated TNF, TNFRs, and ADAM17 at the protein, transcriptional, and gene levels in COVID-19 patients with different levels of disease severity. In total, 102 patients were divided into mild, moderate, and severe condition groups. A group of healthy donors (HD; n = 25) was included. Our data showed that solTNFR1 and solTNFR2 were elevated among the COVID-19 patients ( p < 0.0001), without increasing the transcriptional level. Only solTNFR1 was higher in the severe group as compared to the mildly ill ( p < 0.01), and the level was higher in COVID-19 patients who died than those that survived ( p < 0.0001). The solTNFR1 level had a discrete negative correlation with C-reactive protein ( p = 0.006, Rho = −0.33). The solADAM17 level was higher in severe as compared to mild disease conditions ( p < 0.01), as well as in COVID-19 patients who died as compared to those that survived ( p < 0.001). Additionally, a potential association between polymorphism TNFRSF1A :rs767455 and a severe degree of disease was suggested. These data suggest that solTNFR1 and solADAM17 are increased in severe conditions. solTNFR1 should be considered a potential target in the development of new therapeutic options.
【저자키워드】 COVID-19, severity, ADAM17, solTNF, solTNFR1, solTNFR2, 【초록키워드】 Release, disease severity, polymorphism, C-reactive protein, Protein, Patient, Mild, receptor, disease, Critical, moderate, Inflammatory cytokine, therapeutic options, association, TNF, COVID-19 patient, severe group, negative correlation, pro-inflammatory molecules, overproduction, TNFR1, TNFR2, transcriptional level, TNFRSF1A, transcriptional, healthy donor, died, evaluated, form, elevated, condition, suggested, groups, conditions, those that survived, 【제목키워드】 TNFR1, show, relationship, increase,