Decreased ADAMTS13 Activity During COVID-19 Infection Predicts Future Major Cerebrovascular and Cardiovascular Adverse Events
Philion Gatchoff1, Claire Delpirou Nouh1, Chao Xu1, Andrea Vincent1, Leslie Guthery2, Jason Sharps1, Fabiola Donna-Ferreira2, James George1, Angelia Kirkpatrick1, Calin Prodan1
1University of Oklahoma, 2VA Medical Center - Oklahoma City
Objective:
To examine whether ADAMTS13 activity levels measured at the time of acute SARS-CoV-2 infection predict major cerebrovascular and cardiovascular adverse events (MACE) at 42 months.
Background:
The critical role of ADAMTS13 in thrombosis is exemplified by its importance in pathogenesis of thrombotic thrombocytopenic purpura (TTP). Lower ADAMTS13 activity has been linked to increased risk of incident stroke, myocardial infarction and cardiovascular death in populational studies. COVID-19 patients are at increased risk of thrombotic events during both acute infection and after convalescence.
Design/Methods:
After consent, patients hospitalized with SARS-CoV-2 infection were enrolled. ADAMTS13 activity levels were measured upon admission, then twice weekly during hospitalization. Post-COVID-recovery MACE, defined as occurrence of stroke, myocardial infarction, acute coronary syndrome, pulmonary embolism, DVT or sudden cardiac death were identified by chart review. The distribution of MACE was compared among patients categorized into tertiles of ADAMTS13 activity. Receiver Operator Characteristic (ROC) and survival analyses assessed the predictive value of ADAMTS13 activity at enrollment for future MACE. Significance was set at 0.05. 
Results:
We recruited 39 patients with COVID-19, mean age 68 years (range 37-88 years), followed for an average of 42 (2-48) months. Initial ADAMTS13 levels were 68% (range 12-94%). MACE occurred in 15/39 patients (38.4%): 9 in the lowest (69%), 3 in the middle (21%) and 3 in the highest tertile (25%) of initial ADAMTS13 activity levels (p=0.02). ADAMTS13 activity was associated with MACE (AUC 0.690, 95% CI: 0.503-0.877, p=0.046). Levels <55% were significantly associated with time to earliest MACE (Log-rank test p=0.002), with a HR of 4.30 (95% CI: 1.55-11.92), PPV of 0.778 and NPV of 0.733. 
Conclusions:
Lower ADAMTS13 activity during SARS-CoV-2 infection is associated with increased risk for MACE 42 months after recovery. Future work is needed to investigate the link between ADAMTS13 activity and the long-term risk of major cerebrovascular and cardiovascular events. 
10.1212/WNL.0000000000211127
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