Reduced ADAMTS13 Activity in Correlation with Pathophysiology, Severity, and Outcome of COVID-19: A Retrospective Observational Study

https://doi.org/10.1016/j.ijid.2022.02.019Get rights and content
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Highlights

  • Coagulopathy risk and microthrombosis were noticed in patients with COVID-19

  • ADAMTS13 and the VWF/ADAMTS13 axis could be connected to this risk

  • Low ADAMTS13 was linked to pneumonia, COVID-19 severity, and ventilation need

  • Recombinant ADAMTS13 could be a novel therapeutic strategy for Severe COVID-19

Abstract

Background

Low ADAMTS13 activity has been suggested to be an interplaying factor in the pathogenesis of COVID-19, considering that it is a thromboinflammatory disease with high risk of microthrombosis.

Objectives

The study aimed to explore the correlation between ADAMTS13 activity and the pathophysiological pathway of COVID-19.

Methods

We carried out a retrospective observational study of 87 patients with COVID-19 in NMC Royal Hospital, Abu Dhabi, UAE. ADAMTS13 activity was measured and compared with patients’ characteristics and clinical outcomes.

Results

Low ADAMTS13 activity was associated with pneumonia (p = 0.007), severity of COVID-19 (p <0.001), and mechanical ventilation rates (p = 0.018). Death was more frequently observed among patients (5 patients) with low ADAMTS13 activity compared with normal activity (1 patient), as well as inflammatory markers. Decreased ADAMTS13 activity increased with the risk of pneumonia, severity of COVID-19, need for mechanical ventilation, and use of anticoagulants ([OR = 4.75, 95% CI 1.54–18.02, p = 0.011], [OR = 6.50, 95% CI 2.57–17.74; p <0.001], [OR = 4.10, 95% CI 1.29–15.82; p = 0.024], [OR = 8.00, 95% CI 3.13–22.16; p <0.001], respectively). The low ADAMTS13 activity group had a slightly longer time to viral clearance than the normal ADAMTS13 activity group, but it was not statistically significant (20 days, 95% CI 16–27 days vs 17 days, 95% CI 13–22 days; p = 0.08; Log rank = 3.1).

Conclusions

Low ADAMTS13 activity has been linked to pneumonia, COVID-19 severity, use of anticoagulants, and need for mechanical ventilation but not to mortality. We propose rADAMTS13 as a novel treatment for severe COVID-19.

Keywords

ADAMTS13
Thrombosis
SARS-CoV-2
Cytokine storm
COVID-19
Pneumonia
Anticoagulation

Abbreviations

ADAMTS13
a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13
CAC
Coronavirus-associated coagulopathy
rADAMTS13
Recombinant ADAMTS13
TMA
Thrombotic microangiopathy
VWF
von Willebrand factor
UAE
United Arab Emirates
WPBs
Weibel-Palade bodies

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Medical Research Division, Department of Internal Medicine, The National Research Centre, Cairo, Egypt.