Severe COVID-19 Patients Show an Increase in Soluble TNFR1 and ADAM17, with a Relationship to Mortality
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, transc...
Main Authors: | , , , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-08-01
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Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/22/16/8423 |
Summary: | 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. |
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ISSN: | 1661-6596 1422-0067 |