Dataset Information

Effects of convalescent plasma infusion on the ADAMTS13-von Willebrand factor axis and endothelial integrity in patients with severe and critical COVID-19.

ABSTRACT:

Background

Convalescent plasma infusion (CPI) was given to patients with COVID-19 during the early pandemic with mixed therapeutic efficacy. However, the impacts of CPI on the ADAMTS13-von Willebrand factor (VWF) axis and vascular endothelial functions are not known.

Objectives

To determine the impacts of CPI on the ADAMTS13-VWF axis and vascular endothelial functions.

Methods

Sixty hospitalized patients with COVID-19 were enrolled in the study; 46 received CPI and 14 received no CPI. Plasma ADAMTS13 activity, VWF antigen, endothelial syndecan-1, and soluble thrombomodulin (sTM) were assessed before and 24 hours after treatment.

Results

Patients with severe and critical COVID-19 exhibited significantly lower plasma ADAMTS13 activity than the healthy controls. Conversely, these patients showed a significantly increased VWF antigen. This resulted in markedly reduced ratios of ADAMTS13 to VWF in these patients. The levels of plasma ADAMTS13 activity in each patient remained relatively constant throughout hospitalization. Twenty-four hours following CPI, plasma ADAMTS13 activity increased by ∼12% from the baseline in all patients and ∼21% in those who survived. In contrast, plasma levels of VWF antigen varied significantly over time. Patients who died exhibited a significant reduction of plasma VWF antigen from the baseline 24 hours following CPI, whereas those who survived did not. Furthermore, patients with severe and critical COVID-19 showed significantly elevated plasma levels of syndecan-1 and sTM, similar to those found in patients with immune thrombotic thrombocytopenic purpura. Both syndecan-1 and sTM levels were significantly reduced 24 hours following CPI.

Conclusion

Our results demonstrate the relative deficiency of plasma ADAMTS13 activity and endothelial damage in patients with severe and critical COVID-19, which could be modestly improved following CPI therapy.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC9744678 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Effects of convalescent plasma infusion on the ADAMTS13-von Willebrand factor axis and endothelial integrity in patients with severe and critical COVID-19.

Zhang Quan Q Ye Zhan Z McGowan Paul P Jurief Christopher C Ly Andrew A Bignotti Antonia A Yada Noritaka N Zheng X Long XL

Research and practice in thrombosis and haemostasis 20221213 1

<h4>Background</h4>Convalescent plasma infusion (CPI) was given to patients with COVID-19 during the early pandemic with mixed therapeutic efficacy. However, the impacts of CPI on the ADAMTS13-von Willebrand factor (VWF) axis and vascular endothelial functions are not known.<h4>Objectives</h4>To determine the impacts of CPI on the ADAMTS13-VWF axis and vascular endothelial functions.<h4>Methods</h4>Sixty hospitalized patients with COVID-19 were enrolled in the study; 46 received CPI and 14 recei ...[more]

PMID: 36531671

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Project description: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 (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.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. 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.Results 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.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.

Dataset Information

Effects of convalescent plasma infusion on the ADAMTS13-von Willebrand factor axis and endothelial integrity in patients with severe and critical COVID-19.

Background

Objectives

Methods

Results

Conclusion

Publications

Effects of convalescent plasma infusion on the ADAMTS13-von Willebrand factor axis and endothelial integrity in patients with severe and critical COVID-19.

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