Levels of Vascular Endothelial Growth Factor and Its Association with Pulmonary Embolism in COVID-19.

Coronavirus disease 2019 (COVID-19) is associated with pulmonary embolism, a condition mechanistically related to vascular endothelial growth factor (VEGF). Our objective was to identify whether VEGF levels, measured at hospital admission, may predict the occurrence of pulmonary embolism (and other thrombosis) during hospitalization. Of a total of 139 patients included in the study, a pulmonary embolism occurred in 4%, other thrombosis in 16%, and 80% remained thrombus free. Clinical and laboratory data at admission were similar among groups. VEGF levels were elevated in COVID-19 patients compared with 38 healthy controls (50.7 versus 15.0 pg/mL; P < 0.001), with an area under the receiver operating characteristic curve of 0.776. At a cutoff point >15.7 pg/mL, VEGF showed 64.7% sensitivity, 92.1% specificity, and a positive likelihood ratio of 8.2 to discriminate COVID-19. In COVID-19, VEGF levels were not different in patients with pulmonary embolism, other thrombosis, and thrombus-free patients (15.0 versus 84.0 versus 48.5 pg/mL, respectively; P = 0.19). VEGF correlated with C-reactive protein (ρ = 0.25), fibrinogen (ρ = 0.28), ferritin (ρ = 0.18), and the neutrophil-to-lymphocyte ratio (ρ = 0.20). Our study showed that VEGF is elevated in sera from patients with COVID-19 on arrival at the hospital and its levels correlate with inflammatory markers, although they are unable to predict the appearance of pulmonary embolism during hospitalization.

Tocotrienol-Rich Vitamin E (Tocovid) Improved Nerve Conduction Velocity in Type 2 Diabetes Mellitus Patients in a Phase II Double-Blind, Randomized Controlled Clinical Trial.

Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFß-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.

IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection.

SARS-CoV-2 virus has infected more than 92 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19). Using a rhesus macaque model of SARS-CoV-2 infection, we have characterized the transcriptional signatures induced in the lungs of juvenile and old macaques following infection. Genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs, while pathways associated with collagen formation are downregulated, as also seen in lungs of macaques with tuberculosis. In COVID-19, increasing age is a significant risk factor for poor prognosis and increased mortality. Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. Together, our transcriptomic studies have delineated disease pathways that improve our understanding of the immunopathogenesis of COVID-19.

Evaluation of COVID-19 coagulopathy; laboratory characterization using thrombin generation and nonconventional haemostasis assays.

INTRODUCTION: Patients with COVID-19 are known to have a coagulopathy with a thrombosis risk. It is unknown whether this is due to a generalized humoral prothrombotic state or endothelial factors such as inflammation and dysfunction. The aim was to further characterize thrombin generation using a novel analyser (ST Genesia, Diagnostica Stago, Asnières, France) and a panel of haematological analytes in patients with COVID-19. METHODS: Platelet poor plasma of 34 patients with noncritical COVID-19 was compared with 75 patients with critical COVID-19 (as defined by WHO criteria) in a retrospective study by calibrated automated thrombography and ELISA. Patients were matched for baseline characteristics of age and gender. RESULTS: Critical patients had significantly increased fibrinogen, CRP, interleukin-6 and D-dimer compared to noncritical patients. Thrombin generation, in critical patients, was right shifted without significant differences in peak, velocity index or endogenous thrombin potential. Tissue plasminogen activator (tPA), tissue factor pathway inhibitor (TFPI) and vascular endothelial growth factor (VEGF) were significantly increased in the critical versus noncritical patients. Critically ill patients were on haemodiafiltration (31%; heparin used in the circuit) or often received escalated prophylactic low-molecular weight heparin. CONCLUSION: These results confirm increased fibrinogen and D-dimer in critical COVID-19-infected patients. Importantly, disease severity did not increase thrombin generation (including thrombin-antithrombin complexes and prothrombin fragment 1 + 2) when comparing both cohorts; counter-intuitively critical patients were hypocoaguable. tPA, TFPI and VEGF were increased in critical patients, which are hypothesized to reflect endothelial dysfunction and/or contribution of heparin (which may cause endothelial TFPI/tPA release).

Serum Cytokine and Chemokine Profile in Relation to the Severity of Coronavirus Disease 2019 in China.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the serum cytokine and chemokine levels in asymptomatic, mild, moderate, severe, and convalescent SARS-CoV-2-infected cases. Proinflammatory cytokine and chemokine production induced by SARS-CoV-2 were observed not only in symptomatic patients but also in asymptomatic cases, and returned to normal after recovery. IL-6, IL-7, IL-10, IL-18, G-CSF, M-CSF, MCP-1, MCP-3, IP-10, MIG, and MIP-1α were found to be associated with the severity of COVID-19. Moreover, a set of cytokine and chemokine profiles were significantly higher in SARS-CoV-2-infected male than female patients. The serum levels of MCP-1, G-CSF, and VEGF were weakly and positively correlated with viral titers. We suggest that combinatorial analysis of serum cytokines and chemokines with clinical classification may contribute to evaluation of the severity of COVID-19 and optimize the therapeutic strategies.

Comparison of VEGF-A values between pregnant women with COVID-19 and healthy pregnancies and its association with composite adverse outcomes.

The aim is to compare VEGF-A values between pregnant women with coronavirus disease 2019 (COVID-19) and healthy controls. Furthermore, the association of inflammation parameters, disease severity, and obstetric complications with VEGF-A was investigated. This prospective case-control study was conducted on pregnant women who were admitted to Ankara City Hospital between June 14, 2020 and August 28, 2020. Pregnant women with COVID-19 (n = 95) were compared with a control group of healthy pregnant women (n = 92) with similar clinical and demographic characteristics. Demographic features, clinical characteristics, laboratory test results, VEGF-A values were compared between the groups. A correlation analysis was performed between VEGF-A levels, inflammation parameters, and clinical characteristics of the cases for pregnant women with COVID-19. VEGF-A levels were also compared between patients with composite adverse outcome and patients without any complication in the COVID-19 group. The two groups were similar except for obstetric complications (p > .05). The obstetric complication rate was higher in the COVID-19 group (p =.02). The two groups were comparable in terms of neutrophil to lymphocyte ratio and VEGF-A values. VEGF-A values were slightly different between the trimesters. A negative moderate statistically significant correlation was found between the neutrophil and VEGF-A values (r = -0.231, p =.02). VEGF-A values were similar between patients with and without composite adverse outcomes (p > .05). VEGF-A values were similar between pregnant women with COVID-19 and healthy controls.