Associations between the von Willebrand Factor-ADAMTS13 Axis, Complement Activation, and COVID-19 Severity and Mortality.
Thromb Haemost
; 122(2): 240-256, 2022 Feb.
Article
in English
| MEDLINE | ID: covidwho-1642057
ABSTRACT
BACKGROUND:
Endothelial and complement activation were both associated with immunothrombosis, a key determinant of COVID-19 severity, but their interrelation has not yet been investigated.OBJECTIVES:
We aimed to determine von Willebrand factor (VWF) antigen (VWFAg) concentration, VWF collagen binding activity (VWFCBA), a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (ADAMTS13Ac), and their ratios in hospitalized COVID-19 patients, and to investigate how these parameters and their constellation with complement activation relate to disease severity and in-hospital mortality in COVID-19.METHODS:
Samples of 102 hospitalized patients with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 positivity were included in our observational cohort study. Patients were stratified according to the peak severity of COVID-19 disease in agreement with the World Health Organization ordinal scale. Twenty-six convalescent plasma donors with previous COVID-19 disease formed the control group. VWFAg concentration and VWFCBA were determined by enzyme-linked immunosorbent assay (ELISA); ADAMTS13Ac was determined by fluorescence resonance energy transfer. Complement C3 and C3a were measured by turbidimetry and ELISA, respectively. Clinical covariates and markers of inflammation were extracted from hospital records.RESULTS:
VWFAg and VWFCBA were elevated in all groups of hospitalized COVID-19 patients and increased in parallel with disease severity. ADAMTS13Ac was decreased in patients with severe COVID-19, with the lowest values in nonsurvivors. High (> 300%) VWFAg concentrations or decreased (< 67%) ADAMTS13Ac were associated with higher risk of severe COVID-19 disease or in-hospital mortality. The concomitant presence of decreased ADAMTS13Ac and increased C3a/C3 ratio-indicating complement overactivation and consumption-was a strong independent predictor of in-hospital mortality.CONCLUSION:
Our results suggest that an interaction between the VWF-ADAMTS13 axis and complement overactivation and consumption plays an important role in the pathogenesis of COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Complement C3
/
Von Willebrand Factor
/
ADAMTS13 Protein
/
SARS-CoV-2
/
COVID-19
Type of study:
Cohort study
/
Experimental Studies
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
English
Journal:
Thromb Haemost
Year:
2022
Document Type:
Article
Affiliation country:
S-0041-1740182
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