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Pharmaceuticals (Basel) ; 15(1)2021 Dec 24.
Article in English | MEDLINE | ID: covidwho-1580534


COVID-19 pathophysiology is caused by a cascade of respiratory and multiorgan failures arising, at least in part, from the SARS-CoV-2-driven dysregulation of the master transcriptional factor STAT3. Pharmacological correction of STAT3 over-stimulation, which is at the root of acute respiratory distress syndrome (ARDS) and coagulopathy/thrombosis events, should be considered for treatment of severe COVID-19. In this perspective, we first review the current body of knowledge on the role of STAT3 in the pathogenesis of severe COVID-19. We then exemplify the potential clinical value of treating COVID-19 disease with STAT3 inhibitors by presenting the outcomes of two hospitalized patients with active cancer and COVID-19 receiving oral Legalon®-a nutraceutical containing the naturally occurring STAT3 inhibitor silibinin. Both patients, which were recruited to the clinical trial SIL-COVID19 (EudraCT number: 2020-001794-77) had SARS-CoV-2 bilateral interstitial pneumonia and a high COVID-GRAM score, and showed systemic proinflammatory responses in terms of lymphocytopenia and hypoalbuminemia. Both patients were predicted to be at high risk of critical COVID-19 illness in terms of intensive care unit admission, invasive ventilation, or death. In addition to physician's choice of best available therapy or supportive care, patients received 1050 mg/day Legalon® for 10 days without side-effects. Silibinin-treated cancer/COVID-19+ patients required only minimal oxygen support (2-4 L/min) during the episode, exhibited a sharp decline of the STAT3-regulated C-reactive protein, and demonstrated complete resolution of the pulmonary lesions. These findings might inspire future research to advance our knowledge and improve silibinin-based clinical interventions aimed to target STAT3-driven COVID-19 pathophysiology.

Respir Med Res ; 79: 100826, 2021 May.
Article in English | MEDLINE | ID: covidwho-1221020


BACKGROUND: Early recognition of the severe illness is critical in coronavirus disease-19 (COVID-19) to provide best care and optimize the use of limited resources. OBJECTIVES: We aimed to determine the predictive properties of common community-acquired pneumonia (CAP) severity scores and COVID-19 specific indices. METHODS: In this retrospective cohort, COVID-19 patients hospitalized in a teaching hospital between 18 March-20 May 2020 were included. Demographic, clinical, and laboratory characteristics related to severity and mortality were measured and CURB-65, PSI, A-DROP, CALL, and COVID-GRAM scores were calculated as defined previously in the literature. Progression to severe disease and in-hospital/overall mortality during the follow-up of the patients were determined from electronic records. Kaplan-Meier, log-rank test, and Cox proportional hazard regression model was used. The discrimination capability of pneumonia severity indices was evaluated by receiver-operating-characteristic (ROC) analysis. RESULTS: Two hundred ninety-eight patients were included in the study. Sixty-two patients (20.8%) presented with severe COVID-19 while thirty-one (10.4%) developed severe COVID-19 at any time from the admission. In-hospital mortality was 39 (13.1%) while the overall mortality was 44 (14.8%). The mortality in low-risk groups that were identified to manage outside the hospital was 0 in CALL Class A, 1.67% in PSI low risk, and 2.68% in CURB-65 low-risk. However, the AUCs for the mortality prediction in COVID-19 were 0.875, 0.873, 0.859, 0.855, and 0.828 for A-DROP, PSI, CURB-65, COVID-GRAM, and CALL scores respectively. The AUCs for the prediction of progression to severe disease was 0.739, 0.711, 0,697, 0.673, and 0.668 for CURB-65, CALL, PSI, COVID-GRAM, A-DROP respectively. The hazard ratios (HR) for the tested pneumonia severity indices demonstrated that A-DROP and CURB-65 scores had the strongest association with mortality, and PSI, and COVID-GRAM scores predicted mortality independent from age and comorbidity. CONCLUSION: Community-acquired pneumonia (CAP) scores can predict in COVID-19. The indices proposed specifically to COVID-19 work less than nonspecific scoring systems surprisingly. The CALL score may be used to decide outpatient management in COVID-19.

COVID-19/mortality , Severity of Illness Index , Aged , Aged, 80 and over , Cohort Studies , Disease Progression , Female , Hospital Mortality , Hospitalization , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Turkey/epidemiology