Circulating Cellular Clusters are Correlated with Thrombotic Complications and Clinical Outcomes in COVID-19
Ander Dorken Gallastegi, MD1, Leon Naar, MD1, Elizabeth Van Cott, MD2, Rachel Rosovsky, MD3, David Gregory, PhD4, Damodaran Annamalai, DVM, PhD5, Ronald Tompkins, MD, ScD6, Jarone Lee, MD, MPH7, Haytham M.A. Kaafarani, MD, MPH1, George C. Velmahos, MD, PhD1, Galit H. Frydman, DVM, ScD1,5
1Trauma Emergency Surgery Surgical Critical Care, Department of Surgery, Massachusetts General Hospital & Harvard Medical School, Boston, MA; 2Department of Pathology, Massachusetts General Hospital & Harvard Medical School, Boston, MA; 3Department of Medicine, Massachusetts General Hospital & Harvard Medical School, Boston, MA; 4Department of Pediatrics, Massachusetts General Hospital & Harvard Medical School, Boston, MA; 5Department of Biomedical Engineering & Dvs. Of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA; 6Department of Surgery, Massachusetts General Hospital, Boston, MA; 7Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA
Background: COVID-19 triggers a proinflammatory and prothrombotic state. The role of circulating cellular clusters in COVID-19 remains unclear. This study explores the phenotype of circulating cellular clusters and their potential relationship with thrombotic complications and other clinical outcomes in COVID-19.
Methods: Blood samples were collected between July–August 2020 from patients with a positive SARS-CoV2 PCR. Imaging flow cytometry was used to detect various circulating cellular clusters: platelet-leukocyte aggregates (PLAs), leukocyte clusters (LC), and platelet-erythrocyte aggregates (PEAs)(Figure 1). Cluster phenotypes were compared between controls and patients with COVID-19, and were retrospectively correlated with outcomes.
Results: Forty-six COVID and 12 control samples were analyzed. Patients with COVID-19 had higher PEAs (2.58(±0.17)% vs. 1.41(±0.21)%, p=0.001) and PLAs (151.73(±15.62)% vs. 64.95(±9.74)%, p=0.007) compared to healthy controls. Multiple statistically significant positive correlations were identified between specific cluster types and clinical outcomes (Table 1). LCs, in particular, were significantly correlated with thrombotic events (0.007(±0.006)% vs. 0.010(±0.021)%, p=0.008), whereas PLAs and PEAs were not. Blood type was also correlated to LCs (p=0.021), with Type O having the least LCs, followed by Types A, B and AB.
Conclusion: Circulating immunothrombotic cellular clusters are correlated with the development of thrombotic events and end-organ damage in COVID-19. Further study of the role of the cellular component in the development of COVID-19 sequelae may lead to the identification of novel drug targets for inflammation-related thrombosis.
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