Prognostic Value of Catestatin in Severe COVID-19: An ICU-Based Study

Abstract

Catestatin is a pleiotropic peptide with a wide range of immunomodulatory effects. Considering that patients with a severe COVID-19 infection have a major immunological dysregulation, the aim of this study was to evaluate catestatin levels in patients with COVID-19 treated in the intensive care unit (ICU) and to compare them between the fatal and non-fatal outcomes. The study included 152 patients with severe COVID-19, out of which 105 had a non-fatal outcome and 47 had a fatal outcome. Serum catestatin levels were estimated by an enzyme-linked immunosorbent assay in a commercially available diagnostic kit. The results show that catestatin levels were significantly lower in the fatal group compared to the non-fatal group (16.6 ± 7.8 vs. 23.2 ± 9.2 ng/mL; p < 0.001). Furthermore, there was a significant positive correlation between serum catestatin levels and vitamin D levels (r = 0.338; p < 0.001) while there was also a significant positive correlation between serum catestatin levels and growth differentiation factor-15 (GDF-15) levels (r = −0.345; p < 0.001). Furthermore, multivariate logistic regression showed that catestatin, GDF-15 and leukocyte count were significant predictors for COVID-19 survival. These findings imply that catestatin could be playing a major immunomodulatory role in the complex pathophysiology of the COVID-19 infection and that serum catestatin could also be a predictor of a poor COVID-19 outcome.

Catestatin: Antimicrobial Functions and Potential Therapeutics

“…(ii) CST as an immunomodulatory peptide: Existing literature (expression of CST in innate immune cells [ 21 , 98 , 127 , 151 ], inhibition of macrophage infiltration in tissues [ 97 , 98 , 99 ], decreased expression of pro-inflammatory cytokines by CST [ 97 , 98 ], and low plasma CST in fatal COVID-19 patients [ 129 ]) implicate CST as an immunomodulatory peptide.…”

“…This pathway is in sharp contrast to the nicotinic-cholinergic pathway used by CST to induce catecholamine secretion from chromaffin cells [ 5 ]. Subsequent studies uncover the following: (i) release of immunoreactive CST-containing peptides from human stimulated polymorphonuclear neutrophils [ 21 ]; (ii) detection of CST in mouse peritoneal macrophages by Western blots [ 98 ]; (iii) detection of CST in human monocytes and monocyte-derived macrophages by Western blots [ 127 ]; (iv) blockade of lipopolysaccharide (LPS)-induced increase in expression of tumor necrosis factor alpha [ 127 ]; (v) decreased expression of proinflammatory cytokines by CST in plasma and heart [ 98 ]; (vi) inhibition of infiltration of macrophages in obese liver [ 97 ]; (vii) degranulation of primary mast cells from human peripheral blood [ 128 ]; and (viii) low plasma CST in fatal COVID-19 patients [ 129 ]. These findings implicate CST as an immunomodulatory peptide.…”

Catestatin: Antimicrobial Functions and Potential Therapeutics

“…This pathway is in sharp contrast to the nicotinic-cholinergic pathway used by CST to induce catecholamine secretion from chromaffin cells [5]. Subsequent studies uncover the following: (i) release of immunoreactive CST-containing peptides from human stimulated polymorphonuclear neutrophils [61]; (ii) detection of CST in mouse peritoneal macrophages by Western blots [39]; (iii) detection of CST in human monocytes and monocyte-derived macrophages by Western blots [62]; (iv) blockade of lipopolysaccharide (LPS)-induced increase in expression of tumor necrosis factor alpha (TNF-α) [62]; (v) decreased expression of proinflammatory cytokines by CST in plasma and heart [39]; (vi) inhibition of infiltration of macrophages in obese liver [44]; (vii) degranulation of primary mast cells from human peripheral blood [63] and (viii) low plasma CST in fatal COVID-19 patients [64]. These findings implicate CST as an immunomodulatory peptide.…”

Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease

“…It has been consistently demonstrated that GDF-15 is weakly expressed in all tissue types (except for placenta) under normal physiological states, where it plays a role in cell growth, signal transduction, and apoptosis regulation[ 11 ]. On the other hand, GDF-15 is often over-expressed under stress conditions, such as inflammation, malignancies, heart failure, myocardial ischemia and many others[ 12 - 15 ]. In fact, serum concentrations of GDF-15 were shown to predict poor outcomes in conditions with very variegated pathogenesis, for instance colorectal cancer and heart failure[ 14 , 15 ].…”