Details

Autor(en) / Beteiligte

• Sinkovits, György
• Réti, Marienn
• Müller, Veronika
• Iványi, Zsolt
• Gál, János
• Gopcsa, László
• Reményi, Péter
• Szathmáry, Beáta
• Lakatos, Botond
• Szlávik, János
• Bobek, Ilona
• Prohászka, Zita Z
• Förhécz, Zsolt
• Mező, Blanka
• Csuka, Dorottya
• Hurler, Lisa
• Kajdácsi, Erika
• Cervenak, László
• Kiszel, Petra
• Masszi, Tamás
• Vályi-Nagy, István
• Prohászka, Zoltán

Titel

Associations between the von Willebrand Factor-ADAMTS13 Axis, Complement Activation, and COVID-19 Severity and Mortality

Ist Teil von

• Thrombosis and haemostasis, 2022-02, Vol.122 (2), p.240-256

Ort / Verlag

Germany

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• Endothelial and complement activation were both associated with immunothrombosis, a key determinant of COVID-19 severity, but their interrelation has not yet been investigated.  We aimed to determine von Willebrand factor (VWF) antigen (VWF:Ag) concentration, VWF collagen binding activity (VWF:CBA), a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity (ADAMTS13:Ac), 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.  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. VWF:Ag concentration and VWF:CBA were determined by enzyme-linked immunosorbent assay (ELISA); ADAMTS13:Ac 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.  VWF:Ag and VWF:CBA were elevated in all groups of hospitalized COVID-19 patients and increased in parallel with disease severity. ADAMTS13:Ac was decreased in patients with severe COVID-19, with the lowest values in nonsurvivors. High (> 300%) VWF:Ag concentrations or decreased (< 67%) ADAMTS13:Ac were associated with higher risk of severe COVID-19 disease or in-hospital mortality. The concomitant presence of decreased ADAMTS13:Ac and increased C3a/C3 ratio-indicating complement overactivation and consumption-was a strong independent predictor of in-hospital mortality.  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.