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

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.

Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial.

The effect of routine inhalation therapy on ventilator-associated pneumonia (VAP) in mechanically ventilated patients with the coronavirus disease (COVID-19) has not been well-defined. This randomized controlled trial included 175 eligible adult patients with COVID-19 who were treated with mechanical ventilation at the University Hospital of Split between October 2020 and June 2021. Patients were randomized and allocated to a control group (no routine inhalation) or one of the treatment arms (inhalation of N-acetylcysteine; 5% saline solution; or 8.4% sodium bicarbonate). The primary outcome was the incidence of VAP, while secondary outcomes included all-cause mortality. Routine inhalation therapy had no effect on the incidence of bacterial or fungal VAP nor on all-cause mortality (p > 0.05). Secondary analyses revealed a significant reduction of Gram-positive and methicillin-resistant Staphylococcus aureus (MRSA) VAP in the treatment groups. Specifically, the bicarbonate group had a statistically significantly lower incidence of Gram-positive bacterial VAP (4.8%), followed by the N-acetylcysteine group (10.3%), 5% saline group (19.0%), and control group (34.6%; p = 0.001). This difference was driven by a lower incidence of MRSA VAP in the bicarbonate group (2.4%), followed by the N-acetylcysteine group (7.7%), 5% saline group (14.3%), and control group (34.6%; p < 0.001). Longer duration of ventilator therapy was the only significant, independent predictor of any bacterial or fungal VAP in the multivariate analysis (aOR 1.14, 95% CI 1.01−1.29, p = 0.038 and aOR 1.05, 95% CI 1.01−1.10, p = 0.028, respectively). In conclusion, inhalation therapy had no effect on the overall VAP incidence or all-cause mortality. Further studies should explore the secondary findings of this study such as the reduction of Gram-positive or MRSA-caused VAP in treated patients.

In-Hospital Mortality of COVID-19 Patients Treated with High-Flow Nasal Oxygen: Evaluation of Biomarkers and Development of the Novel Risk Score Model CROW-65.

To replace mechanical ventilation (MV), which represents the cornerstone therapy in severe COVID-19 cases, high-flow nasal oxygen (HFNO) therapy has recently emerged as a less-invasive therapeutic possibility for those patients. Respecting the risk of MV delay as a result of HFNO use, we aimed to evaluate which parameters could determine the risk of in-hospital mortality in HFNO-treated COVID-19 patients. This single-center cohort study included 102 COVID-19-positive patients treated with HFNO. Standard therapeutic methods and up-to-date protocols were used. Patients who underwent a fatal event (41.2%) were significantly older, mostly male patients, and had higher comorbidity burdens measured by CCI. In a univariate analysis, older age, shorter HFNO duration, ventilator initiation, higher CCI and lower ROX index all emerged as significant predictors of adverse events (p < 0.05). Variables were dichotomized and included in the multivariate analysis to define their relative weights in the computed risk score model. Based on this, a risk score model for the prediction of in-hospital mortality in COVID-19 patients treated with HFNO consisting of four variables was defined: CCI > 4, ROX index ≤ 4.11, LDH-to-WBC ratio, age > 65 years (CROW-65). The main purpose of CROW-65 is to address whether HFNO should be initiated in the subgroup of patients with a high risk of in-hospital mortality.