Decreased ADAMTS13 Activity During COVID-19 is Associated with Lower Cognitive Scores After Recovery
Philion Gatchoff1, Claire Delpirou Nouh5, Chao Xu1, Andrea Vincent6, Leslie Guthery1, Jason Sharps1, Jim Scott2, James George3, Angelia Kirkpatrick4, Calin Prodan1
1Neurology, 2Psychiatry, 3Biostatistics and Epidemiology, 4Medicine, University of Oklahoma Health Science Center, 5Neurology, Stanford University, 6Cognitive Science Research Center, University of Oklahoma
Objective:
To examine whether ADAMTS13 activity levels measured at the time of acute SARS-CoV-2 infection predict cognitive impairment after recovery.
Background:
The critical role of ADAMTS13 in thrombosis is exemplified by its importance in the pathogenesis of thrombotic thrombocytopenic purpura (TTP). Lower ADAMTS13 activity has been linked to increased risk for incident stroke in populational studies and TTP cohorts. COVID-19 patients have an increased risk of thrombotic events and microthrombosis, and have increased risk for long-term cognitive symptoms. Lower levels of ADAMTS13 have been reported in COVID-19 patients with severe compared to those with mild infection.
Design/Methods:
After consent, patients hospitalized with SARS-CoV-2 infection were enrolled. ADAMTS13 activity levels were measured upon admission and then twice weekly during hospitalization. Presence of long-COVID symptoms was evaluated with the CDC questionnaire. Cognitive screening was performed via telephone using the MoCA -BLIND, version 8.1. Regression analysis was used to evaluate the effect of clinical variables, demographics, and ADAMTS13 activity on MoCA score.
Results:
We recruited 39 patients with COVID-19, mean age 68 years (range 37-88). Among the 32 (of 39) surviving patients screened for long-COVID symptoms at approximately 16 months after infection, 20 (62.5%) reported ≥1 symptoms, with neurological symptoms present in 18 (56%). Among the 30 patients who completed MoCA testing, mean MoCA score was 16.8; 14 (47%) screened positive for cognitive impairment. Initial ADAMTS13 levels were 68% (range 12-94%), with a significant decrease during admission (p=0.032). ADAMTS13 levels measured at enrollment during COVID-19 hospitalization directly correlated with MoCA scores after adjusting for age and disease severity (adjusted R2=0.28, p=0.019). A 10% decrease in ADAMTS13 activity corresponded to a 1-point decrease in MoCA score (p=0.007).
Conclusions:
Lower ADAMTS13 activity is associated with decreased cognitive performance after recovery from SARS-CoV-2 infection. Future work is needed to investigate the link between ADAMTS13 activity and post-COVID cognitive decline.