Abstract
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.
Highlights
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]
We found that a high level of solTNFR1 correlated with a low level of C-reactive protein (CRP) (p = 0.006, Rho = −0.33) (Figure 6D), which was not observed in solTIM3 (p = 0.913, Rho = 0.01) (Figure 6E)
In accordance with the report of Mortaz, we suggest that a high solTNFR1 level is associated with severe COVID-19 patients and, in addition, our data support the evidence that high solTNFR1 levels are related to an increase of solADAM17
Summary
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. It is essential to note that some research groups suggest that the baseline level of TNF is not distinct between mildly, severely, and critically ill patients with COVID-19, but others propose that the TNF level is higher in severely ill COVID-19 patients [6,7,8]. This discrepancy is probably because diverse cells subpopulations regulate TNF production. The TNF level requires an integrated view of immune cell subpopulations
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