Background: Over 5,488,000 cases of coronavirus disease-19 (COVID-19) have been reported since December 2019. We aim to explore risk factors associated with mortality in COVID-19 patients and assess the use of D-dimer as a biomarker for disease severity and clinical outcome. Methods: We retrospectively analyzed the clinical, laboratory, and radiological characteristics of 248 consecutive cases of COVID-19 in Renmin Hospital of Wuhan University, Wuhan, China from January 28 to March 08, 2020. Univariable and multivariable logistic regression methods were used to explore risk factors associated with inhospital mortality. Correlations of D-dimer upon admission with disease severity and in-hospital mortality were analyzed. Receiver operating characteristic curve was used to determine the optimal cutoff level for D-dimer that discriminated those survivors versus non-survivors during hospitalization. Results: Multivariable regression that showed D-dimer > 2.0 mg/L at admission was the only variable associated with increased odds of mortality [OR 10.17 (95% CI 1.10-94.38), P = 0.041]. D-dimer elevation (≥ 0.50 mg/L) was seen in 74.6% (185/248) of the patients. Pulmonary embolism and deep vein thrombosis were ruled out in patients with high probability of thrombosis. D-dimer levels significantly increased with increasing severity of COVID-19 as determined by clinical staging (Kendall's tau-b = 0.374, P = 0.000) and chest CT staging (Kendall's tau-b = 0.378, P = 0.000). In-hospital mortality rate was 6.9%. Median D-dimer level in non-survivors (n = 17) was significantly higher than in survivors (n = 231) [6.21 (3.79-16.01) mg/L versus 1.02 (0.47-2.66) mg/L, P = 0.000]. D-dimer level of > 2.14 mg/L predicted in-hospital mortality with a sensitivity of 88.2% and specificity of 71.3% (AUC 0.85; 95% CI = 0.77-0.92). Conclusions: D-dimer is commonly elevated in patients with COVID-19. D-dimer levels correlate with disease severity and are a reliable prognostic marker for in-hospital mortality in patients admitted for COVID-19.

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Background: Coronavirus disease 2019 , caused by a novel coronavirus (designated as SARS-CoV-2) has become a pandemic worldwide. Based on the current reports, hypertension may be associated with increased risk of sever condition in hospitalized COVID-19 patients. Angiotensin-converting enzyme 2 (ACE2) was recently identified to functional receptor of SARS-CoV-2. Previous experimental data revealed ACE2 level was increased following treatment with ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Currently doctors concern whether these commonly used renin-angiotensin system (RAS) blockers-ACEIs/ARBs may increase the severity of COVID-19.Methods: We extracted data regarding 50 hospitalized hypertension patients with laboratory confirmed COVID-19 in the Renmin Hospital of Wuhan University from Feb 7 to Mar 03, 2020. These patients were grouped into RAS blockers group (Group A, n=20) and non-RAS blockers group (Group B, n=30) according to the basic blood pressure medications. All patients continued to use pre-admission antihypertensive drugs.Clinical severity (symptoms, laboratory and chest CT findings, etc.), clinical course, and short time outcome were analyzed after hospital admission.Results: Ten (50%) and seventeen (56.7%) of the Group A and Group B participants were males (P=0.643), and the average age was 52.65±13.12 and 67.77±12.84 years (P=0.000), respectively. The blood pressure of both groups was under effective control. There was no significant difference in clinical severity, clinical course and in-hospital mortality between Group A and Group B. Serum cardiac troponin I (cTnI) (P=0.03), and N-terminal (NT)-pro hormone BNP (NT-proBNP) (P=0.04) showed significant lower level in Group A than in Group B. But the patients with more than 0.04ng/mL or elevated NT-proBNP level had no statistical significance between the two groups. In patients over 65 years or under 65 years, cTnI or NT-proBNP level showed no difference between the two groups. Conclusions:We observed there was no obvious difference in clinical characteristics between RAS blockers and non-RAS blockers groups. These data suggest ACEIs/ARBs may have few effects on increasing the clinical severe conditions of COVID-19.

Rationale: Angiogenesis is a crucial step towards tissue repair and regeneration after ischemia. The role of circulating exosomes in angiogenic signal transduction has not been well elucidated. Thus, this study aims to investigate the effects of coronary serum exosomes from patients with myocardial ischemia on angiogenesis and to elucidate the underlying mechanisms.Methods and Results: The patients were enrolled according to the inclusion and exclusion criteria. Coronary blood was obtained from the angiography catheter. Serum exosomes were purified and characterized by their specific morphology and surface markers. In vitro analysis showed that compared to exosomes from healthy controls (con-Exo), exosomes from patients with myocardial ischemia (isc-Exo) enhanced endothelial cell proliferation, migration and tube formation. In a mouse hind-limb ischemia model, blood perfusion and histological staining demonstrated that isc-Exo significantly promoted blood flow recovery and enhanced neovascularization compared to con-Exo. Further, we revealed that cardiomyocytes, but not cardiac fibroblasts or endothelial cells, were initiated to release exosomes under ischemic stress; cardiomyocytes might be the source of bioactive exosomes in coronary serum. In addition, microarray analysis indicated that miR-939-5p was significantly down-regulated in isc-Exo. By knockdown and overexpression analyses, we found that miR-939-5p regulated angiogenesis by targeting iNOS. miR-939-5p inhibited both iNOS's expression and its activity, attenuated endothelial NO production, and eventually impaired angiogenesis.Conclusions: Exosomes derived from patients with myocardial ischemia promote angiogenesis via the miR-939-iNOS-NO pathway. Our study highlights that coronary serum exosomes serve as an important angiogenic messenger in patients suffering from myocardial ischemia.

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An anti-CD133 antibody multilayer functionalized by heparin/collagen on an expanded polytetrafluoroethylene (ePTFE) graft was developed to accelerate early endothelialization. The surface modification of ePTFE grafts demonstrated that the multilayer is stable in static incubation and shaking conditions and that the anti-CD133 antibodies were successfully cross-linked onto the surface. Blood compatibility tests revealed that the coimmobilized heparin/collagen films in the presence or absence of anti-CD133 antibodies prolonged the blood coagulation time and that there was less platelet activation and aggregation, whereas the hemolysis rate was comparable with the bare ePTFE grafts. Cellular proliferation was not inhibited, as the heparin/collagen synthetic vascular grafts coated with CD133 antibody showed little cytotoxicity. The endothelial cells adhered well to the modified ePTFE grafts during a cell adhesion assay. A porcine carotid artery transplantation model was used to evaluate the modified ePTFE grafts in vivo. The results of histopathological staining and scanning electron microscopy indicated that the anti-CD133 antibody was able to accelerate the attachment of vascular endothelial cells onto the ePTFE grafts, resulting in early rapid endothelialization. The success of the anti-CD133 antibody-functionalized heparin/collagen multilayer will provide an effective selection system for the surface modification of synthetic vascular grafts and improve their use in clinical applications.

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