Circulating cellular clusters are associated with thrombotic complications and clinical outcomes in COVID-19
Ander Dorken‐Gallastegi, Yao Lee, Guansheng Li, He Li, Leon Naar, Xuejin Li, Ting Ye, Elizabeth Van Cott, Rachel Rosovsky, David F. Gregory, Ronald G. Tompkins, George Em Karniadakis, Haytham M.A. Kaafarani, George C. Velmahos, Jarone Lee, Galit H. Frydman
Abstract
We sought to study the role of circulating cellular clusters (CCC) –such as circulating leukocyte clusters (CLCs), platelet-leukocyte aggregates (PLA), and platelet-erythrocyte aggregates (PEA)– in the immunothrombotic state induced by COVID-19. Forty-six blood samples from 37 COVID-19 patients and 12 samples from healthy controls were analyzed with imaging flow cytometry. Patients with COVID-19 had significantly higher levels of PEAs (p value<0.001) and PLAs (p value = 0.015) compared to healthy controls. Among COVID-19 patients, CLCs were correlated with thrombotic complications (p value = 0.016), vasopressor need (p value = 0.033), acute kidney injury (p value = 0.027), and pneumonia (p value = 0.036), whereas PEAs were associated with positive bacterial cultures (p value = 0.033). In predictive in silico simulations, CLCs were more likely to result in microcirculatory obstruction at low flow velocities (≤1 mm/s) and at higher branching angles. Further studies on the cellular component of hyperinflammatory prothrombotic states may lead to the identification of novel biomarkers and drug targets for inflammation-related thrombosis.