Hyperresponsive Platelets and a Reduced Platelet Granule Release Capacity Are Associated with Severity and Mortality in COVID-19 Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is often associated with mild thrombocytopenia and increased platelet reactivity. OBJECTIVE: The aim of the current study was to investigate the adenosine triphosphate (ATP) release kinetics of platelets in hospitalized SARS-CoV-2-infected patients. METHODS: We studied time-dependent platelet activation in whole blood by monitoring the ATP release kinetics upon stimulation with a PAR1 receptor agonist in 41 hospitalized critically ill COVID-19 patients, 47 hospitalized noncritically ill COVID-19 patients, and 30 healthy controls. RESULTS: Our study demonstrated that platelets of critically ill COVID-19 patients were hyper-responsive with a shorter platelet response time (PRT) and a reduced platelet granule release capacity (GRC), probably due to chronic activation. The median PRT of COVID-19 patients admitted to the critical care unit was 10 and 7 seconds shorter than the median PRT in healthy controls and noncritical COVID-19 patients, respectively. Both PRT and GRC were also associated with D-dimer (Spearman r [r s] = -0.51, p < 0.0001 and r s = -0.23, p < 0.05), C-reactive protein (CRP) (r s = -0.59, p < 0.0001 and r s = -0.41, p < 0.01), and neutrophil-to-lymphocyte ratio (NLR) (r s = -0.42, p < 0.0001 and r s = -0.26, p < 0.05). Moreover, an increased PRT and a reduced GRC were associated with an increased mortality (odds ratio [OR]: 18.8, 95% confidence interval [CI]: 6.5-62.8, p < 0.0001 and OR: 4.0; 95% CI: 1.6-10.4, p < 0.01). These relationships remained significant after adjustment for age, sex, D-dimer, CRP, and NLR. CONCLUSION: Using an accessible agonist-induced platelet granule ATP release assay, we show that platelet hyper-responsiveness and reduced platelet GRC in COVID-19 patients were associated with critical illness and mortality.

Determinant Factors of COVID-19 Vaccine Hesitancy Among Adult and Elderly Population in Central Java, Indonesia.

Purpose: The Coronavirus disease (COVID-19) vaccination program has been rolled out to address the pandemic. However, the COVID-19 vaccination coverage rate in Indonesia, especially in Central Java, is low. The study aimed to identify COVID-19 vaccine acceptance and to determine the factors associated with COVID-19 vaccine hesitancy. Participants and Methods: A cross-sectional study was conducted from September to October 2021. A self-reported questionnaire was distributed to participants aged ≥ 18 years and living permanently in the area of study by the multistage sampling technique. Bivariate and multivariate analyses were performed to determine the association. All statistical tests were significantly considered if the p-value <0.05 at 95% confidence interval (CI). Results: A total of 500 participants were eligible, with the age ranging from 18 to 76 years old. COVID-19 vaccine acceptance rate was 93.6%. In the multivariate logistic regression analysis, we found that the elderly (aOR=5.231; 95% CI=1.891-14.468), having comorbidity (aOR=4.808; 95% CI=1.975-11.706), not being exposed to information (aOR=7.039; 95% CI=2.072-23.908), not believing in the vaccine halalness (OR=3.802; 95% CI=1.272-11.364), not believing that vaccines could prevent the COVID-19 infection (OR=4.964; 95% CI=1.970-12.507), and having vaccination-related mild-moderate anxiety (OR=14.169; 95% CI=2.405-83.474) were more likely to have vaccine hesitancy (p<0.05). Place of residence, education level, belief that the vaccine could prevent the severe symptoms of COVID-19, and knowledge were significantly related to the vaccine acceptance in the bivariate analysis (p<0.05), but they were no longer significant in the multivariate (p>0.05). Conclusion: A high acceptance rate of the COVID-19 vaccine was found in this study. However, vaccine hesitancy is a major public health concern for attaining herd immunity and reducing the risk of case mortality. These findings could be the strategic focus for the government to improve COVID-19 vaccination coverage.

Increased Plasma Heparanase Activity and Endothelial Glycocalyx Degradation in Dengue Patients Is Associated With Plasma Leakage.

Background: Endothelial hyper-permeability with plasma leakage and thrombocytopenia are predominant features of severe dengue virus infection. It is well established that heparanase, the endothelial glycocalyx degrading enzyme, plays a major role in various diseases with vascular leakage. It is yet to be elucidated whether heparanase activity plays a major role in dengue-associated plasma leakage. Moreover, the major source of heparanase secretion and activation in dengue remains elusive. Since a relatively high amount of heparanase is stored in platelets, we postulate that heparanase released by activated platelets contributes to the increased plasma heparanase activity during dengue virus infection. Methods: Heparanase activity (plasma and urine), and heparan sulfate and syndecan-1 (plasma levels) were measured in dengue patients with thrombocytopenia in acute phase (n=30), during course of disease (n=10) and in convalescent phase (n=25). Associations with clinical parameters and plasma leakage markers were explored. Platelets from healthy donors were stimulated with dengue non-structural protein-1, DENV2 virus and thrombin to evaluate heparanase release and activity ex vivo. Results: Heparanase activity was elevated in acute dengue and normalized during convalescence. Similarly, glycocalyx components, such as heparan sulfate and syndecan-1, were increased in acute dengue and restored during convalescence. Increased heparanase activity correlated with the endothelial dysfunction markers heparan sulfate and syndecan-1, as well as clinical markers of plasma leakage such as ascites, hematocrit concentration and gall-bladder wall thickening. Notably, platelet number inversely correlated with heparanase activity. Ex vivo incubation of platelets with thrombin and live DENV2 virus, but not dengue virus-2-derived non-structural protein 1 induced heparanase release from platelets. Conclusion: Taken together, our findings suggest that the increase of heparanase activity in dengue patients is associated with endothelial glycocalyx degradation and plasma leakage. Furthermore, thrombin or DENV2 activated platelets may be considered as a potential source of heparanase.