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

• Main Authors: Yadira Palacios, Andy Ruiz, Lucero A. Ramón-Luing, Ranferi Ocaña-Guzman, Omar Barreto-Rodriguez, Anahí Sánchez-Monciváis, Brenda Tecuatzi-Cadena, Ana G. Regalado-García, Rey David Pineda-Gudiño, Alicia García-Martínez, Fortunato Juárez-Hernández, Juan Pablo Farias-Contreras, Ingrid Fricke-Galindo, Gloria Pérez-Rubio, Ramcés Falfán-Valencia, Ivette Buendia-Roldan, Karen Medina-Quero, Leslie Chavez-Galan
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: International Journal of Molecular Sciences
• Subjects: COVID-19; solTNF; solTNFR1; solTNFR2; ADAM17; severity
• Online Access: https://www.mdpi.com/1422-0067/22/16/8423

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; <i>n</i> = 25) was included. Our data showed that solTNFR1 and solTNFR2 were elevated among the COVID-19 patients (<i>p</i> < 0.0001), without increasing the transcriptional level. Only solTNFR1 was higher in the severe group as compared to the mildly ill (<i>p</i> < 0.01), and the level was higher in COVID-19 patients who died than those that survived (<i>p</i> < 0.0001). The solTNFR1 level had a discrete negative correlation with C-reactive protein (<i>p</i> = 0.006, Rho = −0.33). The solADAM17 level was higher in severe as compared to mild disease conditions (<i>p</i> < 0.01), as well as in COVID-19 patients who died as compared to those that survived (<i>p</i> < 0.001). Additionally, a potential association between polymorphism <i>TNFRSF1A</i>: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.