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
em En
| MEDLINE
| ID: mdl-35062036
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Complemento C3
/
Fator de von Willebrand
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Proteína ADAMTS13
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SARS-CoV-2
/
COVID-19
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
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Female
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Humans
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Male
/
Middle aged
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article