ABSTRACT
Atrial fibrillation (AF) is the most frequent form of cardiac arrhythmia in COVID-19 infected patients. The occurrence of AF paroxysms is often associated with the acute period of infection in time. At the same time, the pathophysiological mechanisms of the occurrence of AF associated with COVID-19 remain insufficiently studied. The review considers the available literature data on the influence of factors such as reduced availability of angiotensin-converting enzyme 2 receptors, interaction of the virus with the cluster of differentiation 147 and sialic acid, increased inflammatory signaling, "cytokine storm", direct viral damage to the endothelium, electrolyte and acid-alkaline balance in the acute phase of severe illness and increased sympathetic activity.Copyright © Autors 2023.
ABSTRACT
Introduction: Endothelial dysfunction and coagulopathy have been reported as the basis of severe Acute Kidney Injury (AKI) associated with COVID-19. Endothelial biomarkers can detect kidney damage early and allow the adoption of efficient measures to prevent the progression of the disease and its complications. This finding could facilitate the follow-up of patients at higher risk, as well as provide early diagnosis strategies and promote the rational use of resources. The aim of this study is to assess the role of vascular biomarkers to predict the need for hemodialysis in critically ill patients with COVID-19. Method(s): This is a prospective study with 58 patients critically ill due to COVID-19 infection admitted to a tertiary hospital in Fortaleza, Northeast Brazil, from 2020 to 2021. General laboratory tests and vascular biomarkers such as VCAM-1, Syndecan-1, ACE-2, ICAM-1, Angiopoietin-1 and Angiopoietin-2 were quantified on admission to the intensive care unit (ICU). Result(s): There was a 40% mortality rate. VCAM and the Ang-2/Ang-1 ratio at ICU admission were associated with the need for hemodialysis. Vascular biomarkers (VCAM-1, Syndecan-1, angiopoietin-2/anogiopoietin-1 ratio) and thrombocytopenia were predictors of dialysis, and their cutoff values were useful to stratify patients with worse prognosis in the Kaplan-Meier analysis. In the cox multivariate regression analysis with models adjusted according to the presence or absence of platelets, VCAM-1 [O.R. 1.13 (95% CI: 1.01 - 1.27);p=0.034] was an independent predictor of dialysis in all models, and the Ang-2/Ang-1 ratio [O.R. 4.87 (95% C.I.: 1.732 - 13.719);p=0.003] was associated with the need for dialysis in the model without platelet input. Conclusion(s): Vascular biomarkers, mainly VCAM-1 and Ang-2/Ang-1 ratio, and coagulation disorders showed important predictive value for the need for hemodialysis in critically ill patients with COVID-19. No conflict of interestCopyright © 2023
ABSTRACT
Disorders in pulmonary vascular integrity are a prominent feature in many lung diseases, including acute respiratory distress syndrome (ARDS), capillary leak syndrome, and COVID19. Paracrine signals are enriched in the lung and are critically important in regulating the homeostasis of the functional pulmonary microvasculature. Here, we employed single-cell RNA-sequencing (scRNAseq) to study ligand and receptor interactions in the native human lung microvascular niche, and identified soluble factors that are critical in endothelial integrity. The scRNAseq data reveals a total of 47 cell populations consisting of five vascular endothelial subtypes in human lungs, including general capillary EC, aerocyte capillary EC (EC aCap), arterial EC, pulmonary venous EC, and systemic venous EC. Using EC aCap as a signal receiving core (Receptors) and the putative adjacent cell types (alveolar fibroblast, ATI, ATII, pericyte, plasma cell, etc.) in the EC aCap niche as senders (Ligands), we identified that SLIT2-ROBO4, ANGPT1-TIE1, ADM-RAMP2, VEGFD-KDR, and BMP5-BMPR2 are the top specific and abundant pairs in the niche. Immunostaining and ELISA assays confirmed their spatial information and secretion level. Furthermore, upon treatment with these ligands, real-time resistance recorded using an electric cell-substrate impedance sensing (ECIS) system revealed that VEGFD, ANGPT1 (angiopoietin 1), and ADM (adrenomedullin) could markedly increase the electrical resistance of human lung microvascular, arterial, and venous endothelial cells, suggesting their strong impact on the endothelial barrier function. Deciphering the cell-cell soluble signals that improve endothelial integrity in human lungs lays the foundation for uncovering the pathogenesis of pulmonary vascular disorders and the development of ex vivo functional lung vasculature.
ABSTRACT
BACKGROUND & AIMS: Endothelial injury and dysfunction play a detrimental role in the pathogenesis of infections. Endothelium-related molecules have been reported as potential diagnostic and/or prognostic biomarkers of infection. The prognostic value of these biomarkers in patients with cirrhosis and infections remains elusive. METHODS: In this study, we investigated the performance of key soluble endothelial injury biomarkers, including intercellular adhesion molecule 1 (ICAM1), von Willebrand factor (vWF), vascular endothelial growth factor receptor 1 (VEGFR1), and angiopoietin 1 and 2 (Ang1, 2) as mortality predictors in patients with cirrhosis and severe COVID-19 or bacterial sepsis. RESULTS: A total of 66 hospitalized patients (admitted to the COVID-19 ward or liver intensive care unit [ICU]) were included. Twenty-two patients had COVID-19 alone, while 20 patients had cirrhosis plus COVID-19. Twenty-four patients had cirrhosis plus bacterial sepsis. Among patients with cirrhosis, the most common aetiology of liver disease was alcohol. ICAM1 was increased (p = 0.003) while VEGFR1 (p <0.0001) and Ang1 (p <0.0001) were reduced in patients with COVID-19 and cirrhosis, compared to patients with COVID-19 alone. Endothelial biomarker levels did not differ significantly between patients with cirrhosis and severe COVID-19 or bacterial sepsis in the ICU. In these patients, ICAM1 levels significantly and independently predicted mortality (hazard ratio 3.24; 95% CI 1.19-8.86) along with model for end-stage liver disease (MELD) score, renal and coagulation failures. The AUC for ICAM1 was 0.74, MELD was 0.60 and combined ICAM1 and MELD was 0.70. ICAM1 also positively correlated with the composite organ failure scores recorded 3-5 days post ICU admission (CLIF-OF and SOFA) in this subgroup of patients. CONCLUSION: The study indicates that in patients with cirrhosis, elevated plasma ICAM1 serves as an independent predictor of severe COVID-19- or sepsis-associated 28-day mortality. LAY SUMMARY: Bacterial sepsis and COVID-19 lead to increased mortality in patients with cirrhosis. In this study, we demonstrate that high plasma levels of ICAM1, an endothelial injury biomarker, is one of the important factors predicting mortality in critically ill cirrhotic patients with severe COVID-19 or bacterial sepsis.