Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium

Nature Reviews Cardiology, Journal Year: 2022, Volume and Issue: 19(7), P. 475 - 495

Published: Jan. 13, 2022

Language: Английский

---

Immune dysregulation and immunopathology induced by SARS-CoV-2 and related coronaviruses — are we our own worst enemy?

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(1), P. 47 - 56

Published: Nov. 26, 2021

Human coronaviruses cause a wide spectrum of disease, ranging from mild common colds to acute respiratory distress syndrome and death. Three highly pathogenic human — severe coronavirus (SARS-CoV), Middle East SARS-CoV-2 have illustrated the epidemic pandemic potential coronaviruses, better understanding their disease-causing mechanisms is urgently needed for rational design therapeutics. Analyses patients revealed marked dysregulation immune system in cases infection, there ample evidence that aberrant responses are typified by impaired induction interferons, exuberant inflammatory delayed adaptive responses. In addition, various viral proteins been shown impair interferon signalling induce inflammasome activation. This suggests disease associated with mediated both dysregulated host active interference. Here we discuss our current involved each these scenarios. this Perspective, Lok-Yin Roy Wong Stanley Perlman consider how 2 (SARS-CoV-2) related able drive immunopathology. They provide an overview coronavirus-derived molecules interfere key innate responses, including pathways complement, NF-κB activation, as well activation immunity.

Language: Английский

---

Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19

Viruses, Journal Year: 2020, Volume and Issue: 13(1), P. 29 - 29

Published: Dec. 26, 2020

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily illness, extrapulmonary manifestations COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction endothelium during may exacerbate these deleterious events inciting inflammatory microvascular thrombotic processes. controversial, there is evidence SARS-CoV-2 infect endothelial cells binding angiotensin-converting enzyme 2 (ACE2) cellular receptor using viral Spike protein. In this review, we explore current insights into relationship between infection, due ACE2 downregulation, pulmonary extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical clinical development therapeutic agents targeting SARS-CoV-2-mediated dysfunction. Finally, present replication primary human lung cardiac cells. Accordingly, striving understand parameters lead patients, it important consider how direct infection contribute process.

Language: Английский

---

Circulating Von Willebrand factor and high molecular weight multimers as markers of endothelial injury predict COVID-19 in-hospital mortality

Angiogenesis, Journal Year: 2021, Volume and Issue: 24(3), P. 505 - 517

Published: Jan. 15, 2021

Language: Английский

---

Vasculopathy in COVID-19

Blood, Journal Year: 2022, Volume and Issue: 140(3), P. 222 - 235

Published: Jan. 5, 2022

Language: Английский

---

The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Feb. 23, 2022

Abstract The coronavirus disease 2019 (COVID-19) is a highly transmissible caused by the severe acute respiratory syndrome 2 (SARS-CoV-2) that poses major threat to global public health. Although COVID-19 primarily affects system, causing pneumonia and distress in cases, it can also result multiple extrapulmonary complications. pathogenesis of damage patients with probably multifactorial, involving both direct effects SARS-CoV-2 indirect mechanisms associated host inflammatory response. Recognition features complications has clinical implications for identifying progression designing therapeutic strategies. This review provides an overview from immunological pathophysiologic perspectives focuses on potential targets management COVID-19.

Language: Английский

---

ICU Admission Levels of Endothelial Biomarkers as Predictors of Mortality in Critically Ill COVID-19 Patients

Cells, Journal Year: 2021, Volume and Issue: 10(1), P. 186 - 186

Published: Jan. 19, 2021

Endotheliopathy is suggested to be an important feature of COVID-19 in hospitalized patients. To determine whether endotheliopathy involved COVID-19-associated mortality, markers endothelial damage were assessed critically ill patients upon intensive care unit (ICU) admission. Thirty-eight included this observational study, 10 whom died the ICU. Endothelial biomarkers, including soluble (s)E-selectin, sP-selectin, angiopoietin 1 and 2 (Ang-1 Ang-2, respectively), intercellular adhesion molecule (sICAM-1), vascular growth factor (VEGF), (VE)-cadherin, von Willebrand (vWf), measured ICU The cohort was subsequently divided into survivors non-survivors; Kaplan–Meier analysis used explore associations between biomarkers survival, while receiver operating characteristic (ROC) curves generated their potential prognostic value. sE-selectin, sICAM-1 significantly elevated non-survivors compared survivors, also associated with a higher mortality probability analysis. values from ROC greater than 0.85. Hence, we conclude that our cohort, had levels specific survivors. Elevated these admission could possibly predict COVID-19.

Language: Английский

---

Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis

Seminars in Thrombosis and Hemostasis, Journal Year: 2021, Volume and Issue: 47(04), P. 400 - 418

Published: April 23, 2021

Abstract von Willebrand factor (VWF) is a large adhesive multimeric protein involved in hemostasis. The larger the size (or number of VWF multimers), greater functionality protein. A deficiency or defect can lead to disease (VWD) and cause bleeding. Conversely, an increase may create environment that promotes thrombosis. ADAMS-13 (a disintegrin metalloproteinase with thrombospondin type 1 motif, member 13), sometimes called VWF-cleaving protease, primarily responsible for controlling VWF. most severe (<10% normal levels) ADAMTS-13 arises thrombotic thrombocytopenic purpura, condition characterized by presence ultralarge clinically resulting enhanced risk However, result from other pathological processes. Of relevance recent finding COVID-19 (coronavirus 2019) associated both increased levels activity as well generally decreased occasionally normal) ADAMTS-13. Thus, there alteration VWF/ADAMTS-13 axis, often described ratio reduced ADAMTS-13/VWF ratio). also high prothrombotic risk. imbalance be providing milieu (micro)thrombosis, clinical picture resembling secondary microangiopathy some patients. This review therefore assesses literature on VWF, ADAMTS-13, COVID-19. Whenever reported COVID-19, has always been identified raised (compared reference ranges control populations). Reports have included level (i.e., antigen) cases one more “activity” (e.g., collagen binding; platelet glycoprotein Ib [GPIb] binding, using ristocetin cofactor modern versions including VWF:GPIbR [recombinant] VWF:GPIbM [mutant]). reported, “normal” reduced; however, it should recognized still identify relative reduction individual cases. Some reports discuss ADAMTS-13/VWF) ratio, but very few provide actual numerical data.

Language: Английский

---

Autoantibodies and SARS-CoV2 infection: The spectrum from association to clinical implication: Report of the 15th Dresden Symposium on Autoantibodies

Autoimmunity Reviews, Journal Year: 2021, Volume and Issue: 21(3), P. 103012 - 103012

Published: Dec. 9, 2021

The relation between infections and autoimmune diseases has been extensively investigated. Multiple studies suggest a causal these two entities with molecular mimicry, hyperstimulation dysregulation of the immune system as plausible mechanisms. recent pandemic new virus, i.e., SARS-CoV-2, resulted in numerous addressing potential this virus to induce autoimmunity and, eventually, disease. In addition, it also revealed that pre-existing auto-immunity (auto-Abs neutralizing type I IFNs) could cause life-threatening Therefore, topic 15th Dresden Symposium on Autoantibodies was focused SARS-CoV-2 era. This report is collection distillation topics presented at meeting.

Language: Английский

---

Endothelial Dysfunction in the Brain

Stroke, Journal Year: 2021, Volume and Issue: 52(5), P. 1895 - 1904

Published: April 2, 2021

The Coronavirus disease 2019 (COVID)-19 pandemic has already affected millions worldwide, with a current mortality rate of 2.2%. While it is well-established that severe acute respiratory syndrome-coronavirus-2 causes upper and lower tract infections, number neurological sequelae have now been reported in large proportion cases. Additionally, the arterial venous thromboses including pulmonary embolism, myocardial infarction, significant cerebrovascular complications. increasing incidence vessel ischemic strokes as well intracranial hemorrhages, frequently younger individuals, associated increased morbidity mortality, raised questions to why brain major target disease. COVID-19 characterized by hypercoagulability alterations hemostatic markers high D-dimer levels, which are prognosticator poor outcome. Together findings fibrin-rich microthrombi, widespread extracellular fibrin deposition various organs hypercytokinemia, this suggests more than viral infection. Evidently, thrombo-inflammatory Endothelial cells constitute lining blood vessels primary targets response, syndrome coronavirus 2 also directly infects endothelial through ACE2 (angiotensin-converting enzyme 2) receptor. Being highly heterogeneous their structure function, differences may govern susceptibility COVID-19. Here, we explored how unique characteristics cerebral endothelium be underlying reason for rates pathology

Language: Английский

---