ABSTRACT
BACKGROUND: The risk for symptomatic COVID-19 requiring hospitalization is higher in the older population. The course of the disease in hospitalised older patients may show significant variation, from mild to severe illness, ultimately leading to death in the most critical cases. The analysis of circulating biomolecules involved in mechanisms of inflammation, cell damage and innate immunity could lead to identify new biomarkers of COVID-19 severity, aimed to improve the clinical management of subjects at higher risk of severe outcomes. In a cohort of COVID-19 geriatric patients (n= 156) who required hospitalization we analysed, on-admission, a series of circulating biomarkers related to neutrophil activation (neutrophil elastase, LL-37), macrophage activation (sCD163) and cell damage (nuclear cfDNA, mithocondrial cfDNA and nuclear cfDNA integrity). The above reported biomarkers were tested for their association with in-hospital mortality and with clinical, inflammatory and routine hematological parameters. Aim of the study was to unravel prognostic parameters for risk stratification of COVID-19 patients. RESULTS: Lower n-cfDNA integrity, higher neutrophil elastase and higher sCD163 levels were significantly associated with an increased risk of in-hospital decease. Median (IQR) values observed in discharged vs. deceased patients were: 0.50 (0.30-0.72) vs. 0.33 (0.22-0.62) for n-cfDNA integrity; 94.0 (47.7-154.0) ng/ml vs. 115.7 (84.2-212.7) ng/ml for neutrophil elastase; 614.0 (370.0-821.0) ng/ml vs. 787.0 (560.0-1304.0) ng/ml for sCD163. The analysis of survival curves in patients stratified for tertiles of each biomarker showed that patients with n-cfDNA integrity < 0.32 or sCD163 in the range 492-811 ng/ml had higher risk of in-hospital decease than, respectively, patients with higher n-cfDNA integrity or lower sCD163. These associations were further confirmed in multivariate models adjusted for age, sex and outcome-related clinical variables. In these models also high levels of neutrophil elastase (>150 ng/ml) appeared to be independent predictor of in-hospital death. An additional analysis of neutrophil elastase in patients stratified for n-cfDNA integrity levels was conducted to better describe the association of the studied parameters with the outcome. CONCLUSIONS: On the whole, biomarkers of cell-free DNA integrity, neutrophil and macrophage activation might provide a valuable contribution to identify geriatric patients with high risk of COVID-19 in-hospital mortality.
ABSTRACT
Introduction: Older adults are at higher risk of morbidity and mortality for COVID-19. Renin angiotensin-system-inhibitors (RASi) were found to have neutral or protective effect against mortality in COVID-19 adult patients. Aim(s): We investigated whether this association was confirmed also in COVID-19 older patients. Method(s): Prospective observational study on 337 hospitalized older adults (aged 80 years and older). We classified the study population according to RASi use before and during hospitalization. A propensity score analysis was also performed to confirm the findings. Result(s): Mean age was 87.4 +/- 6.1 years. Patients taking RASi at home were 147 (43.6%). During hospitalization, 38 patients (11.3% of the entire study population) discontinued RASi, while 57 patients (16.9% of the entire study population) started RASi. In-hospital mortality was 43.9%. Patients taking RASi during hospitalization (patients who maintained their home RASi therapy + patients who started RASi during hospitalization) had a significant lower in-hospital mortality than untreated patients [HR 0.48 (95% CI 0.34-0.67)], even after adjustment for required respiratory support, functional status, albumin, inflammation and cardiac biomarkers. The association between RASi and in-hospital mortality has been found to be more evident in patients with NT-proBNP >= 1800 pg/ml. The analysis on the groups derived from the 'propensity score matching' (58 patients in each group) confirmed these results [HR 0.46 (95% CI 0.23-0.91)]. Conclusion(s): Despite the high risk of death in older COVID-19 patients, RASi therapy during hospitalization was associated with clinically relevant lower in-hospital mortality, likely due to the benefit of RAS modulation on cardiopulmonary system during the acute phase of the disease. Our findings confirm the protective role of RASi even in COVID-19 patients aged 80 years and older.