Effect of Cytomegalovirus Reactivation on Inflammatory Status and Mortality of Older COVID-19 Patients.

Herpesviridae reactivation such as cytomegalovirus (CMV) has been described in severe COVID-19 (COronaVIrusDisease-2019). This study aimed to understand if CMV reactivation in older COVID-19 patients is associated with increased inflammation and in-hospital mortality. In an observational single-center cohort study, 156 geriatric COVID-19 patients were screened for CMV reactivation by RT-PCR. Participants underwent a comprehensive clinical investigation that included medical history, functional evaluation, laboratory tests and cytokine assays (TNF-α, IFN-α, IL-6, IL-10) at hospital admission. In 19 (12.2%) of 156 COVID-19 patients, CMV reactivation was detected. Multivariate Cox regression models showed that in-hospital mortality significantly increased among CMV positive patients younger than 87 years (HR: 9.94, 95% CI: 1.66-59.50). Other factors associated with in-hospital mortality were C-reactive protein (HR: 1.17, 95% CI: 1.05-1.30), neutrophil count (HR: 1.20, 95% CI: 1.01-1.42) and clinical frailty scale (HR:1.54, 95% CI: 1.04-2.28). In patients older than 87 years, neutrophil count (HR: 1.13, 95% CI: 1.05-1.21) and age (HR: 1.15, 95% CI: 1.01-1.31) were independently associated with in-hospital mortality. CMV reactivation was also correlated with increased IFN-α and TNF-α serum levels, but not with IL-6 and IL-10 serum changes. In conclusion, CMV reactivation was an independent risk factor for in-hospital mortality in COVID-19 patients younger than 87 years old, but not in nonagenarians.

Admission high-sensitivity cardiac troponin levels as a prognostic indicator for in-hospital mortality rates in the elderly and very elderly COVID-19 patients.

BACKGROUND: Elevation of cardiac troponin (cTn) is associated with the worst prognosis not only in cardiovascular disease but also in non-cardiovascular disease. The aim of this study is to verify if cTn has a prognostic role in elderly and very elderly coronavirus disease 2019 (COVID-19) patients. METHODS: This study enrolled consecutive COVID-19 elderly patients hospitalized at INRCA hospital, with available admission high sensitivity cardiac troponin T (HS-cTnT) level. Patients were divided into three groups based on HS-cTnT level: group A (Hs-cTnT ≤ 40 pg/ml), group B (Hs-cTnT 41-100 pg/ml), and group C (Hs-cTnT ≥ 101 pg/ml). The correlation between HS-cTnT levels and mortality rates was analyzed. RESULTS: 461 patients (mean age 86 years; 59% female) were divided into group A (261 patients), group B (129 patients), and group C (71 patients). Group C resulted significantly older, more affected by heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and dementia, and with higher levels of creatinine, C-reactive protein, pro-calcitonin, interleukin-6, ferritin, NT-proBNP, D-dimer then group A and group B. Mortality rate increased significantly across groups (group A: 18.4%; group B: 36.4%; group C: 62.0%; p<0.001). Group C had a significant increase in mortality risk compared to group A, both univariate analysis (HR 3.78) and multivariate analysis (model 2 HR 3.10; model 3 HR 3.59; model 4 HR 1.72). CONCLUSION: HS-cTnT has demonstrated a prognostic role in elderly and very elderly COVID-19 patients. HS-cTnT is a simple and inexpensive laboratory exam that gives clinicians important information on mortality risk stratification.

Admission high-sensitivity cardiac troponin levels as a prognostic indicator for in-hospital mortality rates in the elderly and very elderly COVID-19 patients

Background Elevation of cardiac troponin (cTn) is associated with the worst prognosis not only in cardiovascular disease but also in non-cardiovascular disease. The aim of this study is to verify if cTn has a prognostic role in elderly and very elderly coronavirus disease 2019 (COVID-19) patients. Methods This study enrolled consecutive COVID-19 elderly patients hospitalized at INRCA hospital, with available admission high sensitivity cardiac troponin T (HS-cTnT) level. Patients were divided into three groups based on HS-cTnT level: group A (Hs-cTnT ≤ 40 pg/ml), group B (Hs-cTnT 41-100 pg/ml), and group C (Hs-cTnT ≥ 101 pg/ml). The correlation between HS-cTnT levels and mortality rates was analyzed. Results 461 patients (mean age 86 years;59% female) were divided into group A (261 patients), group B (129 patients), and group C (71 patients). Group C resulted significantly older, more affected by heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and dementia, and with higher levels of creatinine, C-reactive protein, pro-calcitonin, interleukin-6, ferritin, NT-proBNP, D-dimer then group A and group B. Mortality rate increased significantly across groups (group A: 18.4%;group B: 36.4%;group C: 62.0%;p<0.001). Group C had a significant increase in mortality risk compared to group A, both univariate analysis (HR 3.78) and multivariate analysis (model 2 HR 3.10;model 3 HR 3.59;model 4 HR 1.72). Conclusion HS-cTnT has demonstrated a prognostic role in elderly and very elderly COVID-19 patients. HS-cTnT is a simple and inexpensive laboratory exam that gives clinicians important information on mortality risk stratification.

Routine laboratory parameters, including complete blood count, predict COVID-19 in-hospital mortality in geriatric patients.

To reduce the mortality of COVID-19 older patients, clear criteria to predict in-hospital mortality are urgently needed. Here, we aimed to evaluate the performance of selected routine laboratory biomarkers in improving the prediction of in-hospital mortality in 641 consecutive COVID-19 geriatric patients (mean age 86.6 ± 6.8) who were hospitalized at the INRCA hospital (Ancona, Italy). Thirty-four percent of the enrolled patients were deceased during the in-hospital stay. The percentage of severely frail patients, assessed with the Clinical Frailty Scale, was significantly increased in deceased patients compared to the survived ones. The age-adjusted Charlson comorbidity index (CCI) score was not significantly associated with an increased risk of death. Among the routine parameters, neutrophilia, eosinopenia, lymphopenia, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, procalcitonin, IL-6, and NT-proBNP showed the highest predictive values. The fully adjusted Cox regressions models confirmed that high neutrophil %, NLR, derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and low lymphocyte count, eosinophil %, and lymphocyte-to-monocyte ratio (LMR) were the best predictors of in-hospital mortality, independently from age, gender, and other potential confounders. Overall, our results strongly support the use of routine parameters, including complete blood count, in geriatric patients to predict COVID-19 in-hospital mortality, independent from baseline comorbidities and frailty.

Circulating miR-320b and miR-483-5p levels are associated with COVID-19 in-hospital mortality.

The stratification of mortality risk in COVID-19 patients remains extremely challenging for physicians, especially in older patients. Innovative minimally invasive molecular biomarkers are needed to improve the prediction of mortality risk and better customize patient management. In this study, aimed at identifying circulating miRNAs associated with the risk of COVID-19 in-hospital mortality, we analyzed serum samples of 12 COVID-19 patients by small RNA-seq and validated the findings in an independent cohort of 116 COVID-19 patients by qRT-PCR. Thirty-four significantly deregulated miRNAs, 25 downregulated and 9 upregulated in deceased COVID-19 patients compared to survivors, were identified in the discovery cohort. Based on the highest fold-changes and on the highest expression levels, 5 of these 34 miRNAs were selected for the analysis in the validation cohort. MiR-320b and miR-483-5p were confirmed to be significantly hyper-expressed in deceased patients compared to survived ones. Kaplan-Meier and Cox regression models, adjusted for relevant confounders, confirmed that patients with the 20% highest miR-320b and miR-483-5p serum levels had three-fold increased risk to die during in-hospital stay for COVID-19. In conclusion, high levels of circulating miR-320b and miR-483-5p can be useful as minimally invasive biomarkers to stratify older COVID-19 patients with an increased risk of in-hospital mortality.