Severe COVID-19 Patients Show an Increase in Soluble TNFR1 and ADAM17, with a Relationship to Mortality

• Published in: International journal of molecular sciences 2021-08, Vol.22 (16), p.8423
• Main Authors: Palacios, Yadira, Ruiz, Andy, Ramón-Luing, Lucero A., Ocaña-Guzman, Ranferi, Barreto-Rodriguez, Omar, Sánchez-Monciváis, Anahí, Tecuatzi-Cadena, Brenda, Regalado-García, Ana G., Pineda-Gudiño, Rey David, García-Martínez, Alicia, Juárez-Hernández, Fortunato, Farias-Contreras, Juan Pablo, Fricke-Galindo, Ingrid, Pérez-Rubio, Gloria, Falfán-Valencia, Ramcés, Buendia-Roldan, Ivette, Medina-Quero, Karen, Chavez-Galan, Leslie
• Format: Article
• Language: English
• Subjects: C-reactive protein; Coronaviruses; COVID-19; Cytokines; Enzymes; Gene expression; Infections; Inflammation; Inflammatory diseases; Mortality; Pneumonia; Polymorphism; Proteins; Severe acute respiratory syndrome coronavirus 2; Transcription; Tumor necrosis factor; Tumor necrosis factor receptors; Tumor necrosis factor-TNF; Viral infections
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22168423

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.