Assessment of plasma Catestatin in COVID-19 reveals a hitherto unknown inflammatory activity with impact on morbidity-mortality.

Introduction: Neuroendocrine cells release Catestatin (CST) from Chromogranin A (CgA) to regulate stress responses. As regards COVID-19 patients (COVID+) requiring oxygen supply, to date nobody has studied CST as a potential mediator in the regulation of immunity. Patients & Methods: Admission plasma CST and CgA - its precursor - concentrations were measured (ELISA test) in 73 COVID+ and 27 controls. Relationships with demographics, comorbidities, disease severity and outcomes were analysed (Mann-Whitney, Spearman correlation tests, ROC curves). Results: Among COVID+, 49 required ICU-admission (COVID+ICU+) and 24 standard hospitalization (COVID+ICU-). Controls were either healthy staff (COVID-ICU-, n=11) or COVID-ICU+ patients (n=16). Median plasma CST were higher in COVID+ than in controls (1.6 [1.02; 3.79] vs 0.87 [0.59; 2.21] ng/mL, p<0.03), with no difference between COVID+ and COVID-ICU+. There was no difference between groups in either CgA or CST/CgA ratios, but these parameters were lower in healthy controls (p<0.01). CST did not correlate with either hypoxia- or usual inflammation-related parameters. In-hospital mortality was similar whether COVID+ or not, but COVID+ had longer oxygen support and more complications (p<0.03). CST concentrations and the CST/CgA ratio were associated with in-hospital mortality (p<0.01) in COVID+, whereas CgA was not. CgA correlated with care-related infections (p<0.001). Conclusion: Respiratory COVID patients release significant amounts of CST in the plasma making this protein widely available for the neural regulation of immunity. If confirmed prospectively, plasma CST will reliably help in predicting in-hospital mortality, whereas CgA will facilitate the detection of patients prone to care-related infections.

Serum Catestatin Level as a Stratification Assessment Tool in Non-Critical COVID-19 Patients.

Introduction: Catestatin (CST) is a peptide with immunomodulatory, anti-inflammatory, and anti-microbial activities. There are only a few studies that have investigated plasma CST levels in COVID-19 patients (mostly in ICU patients). In our work, the aim was to demonstrate serum CST levels and their correlation with clinical outcomes in a group of severe COVID-19 patients admitted to the non-ICU department. Methods: The subjects were 32 patients (25 females, 7 males) admitted to the non-ICU unit for COVID-19 patients. Results: CST levels in our cohort were higher (8.91 ± 7.00) than previously reported CST levels in control subjects. We found a significant positive correlation between serum CST levels and C-reactive protein (r = 0.423, p = 0.008), D-dimers (r = 0.395, p = 0.013), hsTNT (high-sensitivity troponin T) (r = 0.603, p < 0.001), proBNP (N-terminal pro-brain natriuretic peptide) (r = 0.569, p < 0.001), and hospitalization days (r = 0.388, p = 0.014). There was a difference between groups of participants with SOFA <3 (n = 18) and SOFA >=3 (n = 14) in catestatin serum levels (7.25 ± 3.66 vs. 11.05 ± 9.52 ng/mL), but the difference was statistically insignificant (p = 0.065). Conclusion: We considered plasma CST level at hospital admission as a possible tool for early risk assessment in non-critical COVID-19 patients. This study is an attempt to clarify the complex pathophysiological mechanisms present in the development of severe forms of SARS-CoV2 infection.

Chromogranin A plasma levels predict mortality in COVID-19.

BACKGROUND: Chromogranin A (CgA) and its fragment vasostatin I (VS-I) are secreted in the blood by endocrine/neuroendocrine cells and regulate stress responses. Their involvement in Coronavirus 2019 disease (COVID-19) has not been investigated. METHODS: CgA and VS-I plasma concentrations were measured at hospital admission from March to May 2020 in 190 patients. 40 age- and sex-matched healthy volunteers served as controls. CgA and VS-I levels relationship with demographics, comorbidities and disease severity was assessed through Mann Whitney U test or Spearman correlation test. Cox regression analysis and Kaplan Meier survival curves were performed to investigate the impact of the CgA and VS-I levels on in-hospital mortality. RESULTS: Median CgA and VS-I levels were higher in patients than in healthy controls (CgA: 0.558 nM [interquartile range, IQR 0.358-1.046] vs 0.368 nM [IQR 0.288-0.490] respectively, p = 0.0017; VS-I: 0.357 nM [IQR 0.196-0.465] vs 0.144 nM [0.144-0.156] respectively, p<0.0001). Concentration of CgA, but not of VS-I, significantly increased in patients who died (n = 47) than in survivors (n = 143) (median 0.948 nM [IQR 0.514-1.754] vs 0.507 nM [IQR 0.343-0.785], p = 0.00026). Levels of CgA were independent predictors of in-hospital mortality (hazard ratio 1.28 [95% confidence interval 1.077-1.522], p = 0.005) when adjusted for age, number of comorbidities, respiratory insufficiency degree, C-reactive protein levels and time from symptom onset to sampling. Kaplan Meier curves revealed a significantly increased mortality rate in patients with CgA levels above 0.558 nM (median value, log rank test, p = 0.001). CONCLUSION: Plasma CgA levels increase in COVID-19 patients and represent an early independent predictor of mortality.