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

Abstract

Background Low ADAMTS 13 Activity has been suggested as an interplaying factor in the pathogenesis of COVID-19, considering that it is a thrombo-inflammatory disease with high risk of microthrombosis. Objectives The study aimed to explore the correlation between ADAMTS13 activity and the pathophysiological pathway of COVID-19. Patients/Methods We carried out a retrospective observational study of 87 COVID-19 patients in Nmc Royal Hospital, Abu Dhabi, UAE. ADAMTS13 activity was measured and compared with patients' characteristics and clinical outcomes. Results Low ADAMTS13 level 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 to normal activity (1 patient), as well as inflammatory markers. Decreased ADAMTS13 levels increased 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 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). Conclusion 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.

Severe Hemolytic Anemia: Atypical Presentation of Cobalamin Deficiency

“…Further investigation revealed negative antibodies to ADAMTS13, and the panel for congenital TTP was negative. The remaining hypothesis was that TTP was related to SARS-CoV-2 infection 10 or to a laboratory error. Anemia recurred in 2 weeks, and further investigation revealed a cobalamin deficit, which in a 5-month-old infant that is exclusively breastfed, narrows the differential diagnosis to a maternal deficiency and a primary inherited defect of metabolism.…”

Evaluating the potential mediating role of ADAMTS13 activity in the relationship between obesity and the severity of COVID-19: A retrospective cohort study

“…[37] The time to viral clearance was significantly prolonged in obese patients with low ADAMTS13 activity; the same result was reported by our research team in a previous study. [21] Delayed viral clearance and poor outcomes in obese patients are hallmark findings of several studies. [39,40] Reduced ADAMTS13 activity was one of the most obvious drivers of unmet treatment outcomes in this special patient population, highlighting the importance of rigorous assessment of hospitalized obese COVID-19 patients, regardless of disease severity.…”

“…[ 20 ] In a previous study by our group, we found that reduced ADAMTS13 activity was associated with the development of pneumonia, the need for mechanical ventilation, and the severity of COVID-19; however, there was no statistically significant association with mortality. [ 21 ]…”

Impact of Concomitant Thrombotic Thrombocytopenic Purpura on COVID-19 Mortality and Morbidity: A Nationwide Inpatient Sample Analysis

“…These antibodies neutralize or accelerate the clearance of ADAMTS13, thereby inhibiting the breakdown of vWF. 18,19 This results in the accumulation of oversized vWF multimers in arterioles and capillaries. In light of the recent pandemic, a novel link has been discovered between COVID-19 and TMA conditions, including TTP.…”