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Distinctive Biomarker Features in the Endotheliopathy of COVID-19 and Septic Syndromes.
Fernández, Sara; Moreno-Castaño, Ana B; Palomo, Marta; Martinez-Sanchez, Julia; Torramadé-Moix, Sergi; Téllez, Adrián; Ventosa, Helena; Seguí, Ferran; Escolar, Ginés; Carreras, Enric; Nicolás, Josep M; Richardson, Edward; García-Bernal, David; Carlo-Stella, Carmelo; Moraleda, José M; Richardson, Paul G; Díaz-Ricart, Maribel; Castro, Pedro.
  • Fernández S; Medical Intensive Care Unit, Hospital Clinic, Barcelona, Spain.
  • Moreno-Castaño AB; Hematopathology, Pathology Department, CDB, Hospital Clinic, Barcelona, Spain.
  • Palomo M; Barcelona Endothelium Team, Barcelona, Spain.
  • Martinez-Sanchez J; IDIBAPS, Barcelona, Spain.
  • Torramadé-Moix S; Barcelona Endothelium Team, Barcelona, Spain.
  • Téllez A; Josep Carreras Leukaemia Research Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain.
  • Ventosa H; Barcelona Endothelium Team, Barcelona, Spain.
  • Seguí F; Josep Carreras Leukaemia Research Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain.
  • Escolar G; Hematopathology, Pathology Department, CDB, Hospital Clinic, Barcelona, Spain.
  • Carreras E; Barcelona Endothelium Team, Barcelona, Spain.
  • Nicolás JM; IDIBAPS, Barcelona, Spain.
  • Richardson E; Medical Intensive Care Unit, Hospital Clinic, Barcelona, Spain.
  • García-Bernal D; Medical Intensive Care Unit, Hospital Clinic, Barcelona, Spain.
  • Carlo-Stella C; Medical Intensive Care Unit, Hospital Clinic, Barcelona, Spain.
  • Moraleda JM; Hematopathology, Pathology Department, CDB, Hospital Clinic, Barcelona, Spain.
  • Richardson PG; Barcelona Endothelium Team, Barcelona, Spain.
  • Díaz-Ricart M; IDIBAPS, Barcelona, Spain.
  • Castro P; Barcelona Endothelium Team, Barcelona, Spain.
Shock ; 57(1): 95-105, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1574295
ABSTRACT

BACKGROUND:

Endotheliopathy is a key element in COVID-19 pathophysiology, contributing to both morbidity and mortality. Biomarkers distinguishing different COVID-19 phenotypes from sepsis syndrome remain poorly understood.

OBJECTIVE:

To characterize circulating biomarkers of endothelial damage in different COVID-19 clinical disease stages compared with sepsis syndrome and normal volunteers.

METHODS:

Patients with COVID-19 pneumonia (n = 49) were classified into moderate, severe, or critical (life-threatening) disease. Plasma samples were collected within 48 to 72 h of hospitalization to analyze endothelial activation markers, including soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), von Willebrand Factor (VWF), A disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13 (ADAMTS-13) activity, thrombomodulin (TM), and soluble TNF receptor I (sTNFRI); heparan sulfate (HS) for endothelial glycocalyx degradation; C5b9 deposits on endothelial cells in culture and soluble C5b9 for complement activation; circulating dsDNA for neutrophil extracellular traps (NETs) presence, and α2-antiplasmin and PAI-1 as parameters of fibrinolysis. We compared the level of each biomarker in all three COVID-19 groups and healthy donors as controls (n = 45). Results in critically ill COVID-19 patients were compared with other intensive care unit (ICU) patients with septic shock (SS, n = 14), sepsis (S, n = 7), and noninfectious systemic inflammatory response syndrome (NI-SIRS, n = 7).

RESULTS:

All analyzed biomarkers were increased in COVID-19 patients versus controls (P < 0.001), except for ADAMTS-13 activity that was normal in both groups. The increased expression of sVCAM-1, VWF, sTNFRI, and HS was related to COVID-19 disease severity (P < 0.05). Several differences in these parameters were found between ICU groups SS patients showed significantly higher levels of VWF, TM, sTNFRI, and NETS compared with critical COVID-19 patients and ADAMTS-13 activity was significantly lover in SS, S, and NI-SIRS versus critical COVID-19 (P < 0.001). Furthermore, α2-antiplasmin activity was higher in critical COVID-19 versus NI-SIRS (P < 0.01) and SS (P < 0.001), whereas PAI-1 levels were significantly lower in COVID-19 patients compared with NI-SIRS, S, and SS patients (P < 0.01).

CONCLUSIONS:

COVID-19 patients present with increased circulating endothelial stress products, complement activation, and fibrinolytic dysregulation, associated with disease severity. COVID-19 endotheliopathy differs from SS, in which endothelial damage is also a critical feature of pathobiology. These biomarkers could help to stratify the severity of COVID-19 disease and may also provide information to guide specific therapeutic strategies to mitigate endotheliopathy progression.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Shock Journal subject: Vascular Diseases / Cardiology Year: 2022 Document Type: Article Affiliation country: SHK.0000000000001823

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Shock Journal subject: Vascular Diseases / Cardiology Year: 2022 Document Type: Article Affiliation country: SHK.0000000000001823