Role of endothelial dysfunction in the thrombotic complications of COVID-19 patients

Falcinelli, Emanuela; Petito, Eleonora; Becattini, Cecilia; Robertis, Edoardo De; Paliani, Ugo; Sebastiano, Manuela; Vaudo, Gaetano; Guglielmini, Giuseppe; Paciullo, Francesco; Cerotto, Vittorio; Malvestiti, Marco; Gori, Francesca; Bury, Loredana; Lazzarini, Teseo; Gresele, Paolo

doi:10.1016/j.jinf.2020.11.041

Cited by 22 publications

(37 citation statements)

References 9 publications

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“…The finding of reduced bFMD values in patients with more severe COVID-19 manifestations is consistent with the results of previous cross-sectional, retrospective, and prospective studies, which have shown a significant and direct association between COVID-19 severity and different direct/indirect measures of endothelial function other than bFMD [15][16][17][18]29]. In addition, this finding might support two different albeit not mutually exclusive pathophysiological scenarios in which severe COVID-19 may be either the trigger (i.e., causality) or the consequence (i.e., reverse causality) of endothelial dysfunction.…”

Section: Discussionsupporting

confidence: 91%

“…In the light of these lines of evidence, great interest has arisen in the search for markers of endothelial injury with potential clinical utility for the stratification of COVID-19 prognosis [12,14]. To date, several cross-sectional, retrospective, and prospective studies have reported significant discriminatory value of some laboratory markers of endothelial dysfunction and damage (e.g., circulating endothelial cells, soluble Intercellular Adhesion Molecule 1, and von Willebrand Factor Antigen) toward COVID-19 severity and clinical outcomes [15][16][17][18]. However, to the best of our knowledge, no data are yet available on the potential association between the clinical parameters of endothelial dysfunction and in-hospital outcomes of COVID-19.…”

Section: Introductionmentioning

confidence: 99%

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Low Brachial Artery Flow-Mediated Dilation Predicts Worse Prognosis in Hospitalized Patients with COVID-19

Bianconi

Mannarino

Figorilli

et al. 2021

JCM

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Background: Endothelial injury can be induced by coronavirus disease 2019 (COVID-19) and seems to exert a crucial pathogenic role in its most severe clinical manifestations. We aimed to investigate the association between brachial artery flow-mediated dilation (bFMD), a potential clinical and non-invasive measure of endothelial function, and in-hospital prognosis of COVID-19 patients. Methods: Brachial artery flow-mediated dilation was assessed in hospitalized COVID-19 patients within 48 h of hospital admission. The association between bFMD and either intensive care unit (ICU) admission or in-hospital death was explored using univariable and multivariable analyses. Results: Four hundred and eight patients were enrolled. Significantly lower bFMD values emerged in COVID-19 patients with either radiographic signs of pneumonia, respiratory distress, or the need for non-invasive ventilation compared with patients without these signs (p < 0.001, p = 0.001, and p < 0.001, respectively). Forty-two (10%) patients were admitted to the ICU, 76 (19%) patients died, and 118 (29%) patients met the composite endpoint of ICU admission/in-hospital death. At unadjusted Cox regression analysis showed that low bFMD (<4.4%, the median value) was associated with a higher risk for the composite endpoint of ICU admission/in-hospital death compared with high bFMD (≥4.4%, the median value) (HR 1.675, 95% CI 1.155–2.428, p = 0.007). Multi-adjusted Cox regression analyses showed that low bFMD was independently associated with a 1.519- to 1.658-fold increased risk for the composite endpoint of ICU admission/in-hospital death. Conclusions: Low bFMD predicts an unfavorable in-hospital prognosis in COVID-19 patients. The measurement of bFMD may be clinically useful in the prognostic stratification of COVID-19 patients upon hospital admission.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Low Brachial Artery Flow-Mediated Dilation Predicts Worse Prognosis in Hospitalized Patients with COVID-19

Bianconi

Mannarino

Figorilli

et al. 2021

JCM

View full text Add to dashboard Cite

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“…sVCAM-1 levels were elevated in patients with severe disease compared to patients with mild disease and control participants [14][15][16]. In critically ill patients, no differences between survivors and non-survivors [17].…”

Section: Pf4mentioning

confidence: 85%

Endothelial, Immunothrombotic, and Inflammatory Biomarkers in the Risk of Mortality in Critically Ill COVID-19 Patients: The Role of Dexamethasone

et al. 2021

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Endothelial dysfunction, coagulation and inflammation biomarkers are increasingly emerging as prognostic markers of poor outcomes and mortality in severe and critical COVID-19. However, the effect of dexamethasone has not been investigated on these biomarkers. Hence, we studied potential prognostic biomarkers of mortality in critically ill COVID-19 patients who had either received or not dexamethasone. Biomarker serum levels were measured on intensive care unit (ICU) admission (within 24 h) in 37 dexamethasone-free and 29 COVID-19 patients who had received the first dose (6 mg) of dexamethasone. Receiver operating characteristic (ROC) curves were generated to assess their value in ICU mortality prediction, while Kaplan–Meier analysis was used to explore associations between biomarkers and survival. In the dexamethasone-free COVID-19 ICU patients, non-survivors had considerably higher levels of various endothelial, immunothrombotic and inflammatory biomarkers. In the cohort who had received one dexamethasone dose, non-survivors had higher ICU admission levels of only soluble (s) vascular cell adhesion molecule-1 (VCAM-1), soluble urokinase-type plasminogen activator receptor (suPAR) and presepsin. As determined from the generated ROC curves, sVCAM-1, suPAR and presepsin could still be reliable prognostic ICU mortality biomarkers, following dexamethasone administration (0.7 < AUC < 0.9). Moreover, the Kaplan–Meier survival analysis showed that patients with higher than the median values for sVCAM-1 or suPAR exhibited a greater mortality risk than patients with lower values (Log-Rank test, p < 0.01). In our single-center study, sVCAM-1, suPAR and presepsin appear to be valuable prognostic biomarkers in assessing ICU mortality risk in COVID-19 patients, even following dexamethasone administration.

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“…This was recently confirmed by another report from Italy, showing that patients with COVID-19 had increased circulating endothelial cells and higher plasma levels of soluble intercellular adhesion molecule 1 (sICAM1) and sVCAM1, further supporting the concept of endothelial dysfunction in COVID-19 (ref. 66 ).…”

Section: Immunothrombosis In Covid-19mentioning

confidence: 99%

Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19

et al. 2021

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Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.

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Role of endothelial dysfunction in the thrombotic complications of COVID-19 patients

Cited by 22 publications

References 9 publications

Low Brachial Artery Flow-Mediated Dilation Predicts Worse Prognosis in Hospitalized Patients with COVID-19

Low Brachial Artery Flow-Mediated Dilation Predicts Worse Prognosis in Hospitalized Patients with COVID-19

Endothelial, Immunothrombotic, and Inflammatory Biomarkers in the Risk of Mortality in Critically Ill COVID-19 Patients: The Role of Dexamethasone

Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19

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