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

Abstract

IntroductionNeuroendocrine 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 & MethodsAdmission 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).ResultsAmong 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).ConclusionRespiratory 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.

Chromogranin A and Its Fragments in the Critically Ill: An Expanding Domain of Interest for Better Care

“…Importantly, admission values of CGA significantly increased in those multiple trauma patients who subsequently developed a nosocomial infection: a concentration of 67 ng/mL predicted this occurrence with a sensitivity of 100% and a specificity of 70%, leading to a negative likelihood ratio of almost zero. Recently, we confirmed that admission CGA achieved similar performance for predicting nosocomial infections in COVID patients requiring oxygenation support [ 14 ]. This suggests that CGA may reflect not only the triggering disease but also the neuro-hormonal response by the neuroendocrine tissues.…”

“…They showed that dying COVID patients demonstrated higher CGA levels on admission than survivors. Indeed, in our differently designed study of COVID patients admitted for acute respiratory failure and hypoxemia, admission plasma CGA concentrations instead predicted the occurrence of morbidity rather than mortality, which was better forecast by the CAT/CGA ratio [ 14 ]. Our study suggested that the stressing challenge of COVID was probably not hypoxemia itself—in line with its effect in vitro—since matched ICU control patients without hypoxemia did display levels of CGA similar to those of hypoxic COVID patients [ 37 ].…”

The Editorial Position on ‘Recent Advances in Multifunctional Antimicrobial Peptides as Preclinical Therapeutic Studies and Clinical Future Applications’

“…Another important application for MF-AMPs in human health is their roles as the biomarkers of several diseases both related and unrelated to infections [28][29][30][31]. In this Special Issue, Scnheider and collaborators summarized the biomarker profile of CgA and its derived antimicrobial peptides in the context of critically ill patients [4].…”