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Circulating cellular clusters are associated with thrombotic complications and clinical outcomes in COVID-19

Ander Dorken-Gallastegi1, Yao Lee2, Guansheng Li3

  • 1Division of Trauma, Emergency Surgery, and Surgical Critical Care, Massachusetts General Hospital, Boston, MA 02114, USA.

Iscience
|July 24, 2023
PubMed

Insights

Circulating cellular clusters (CCCs), including platelet-leukocyte aggregates (PLAs) and platelet-erythrocyte aggregates (PEAs), are elevated in COVID-19 patients. These clusters, particularly circulating leukocyte clusters (CLCs), are linked to severe outcomes and microcirculatory obstruction.

Area of Science:

  • Immunology
  • Hematology
  • Pathophysiology

Background:

  • COVID-19 is associated with an immunothrombotic state.
  • Circulating cellular clusters (CCCs) like circulating leukocyte clusters (CLCs), platelet-leukocyte aggregates (PLAs), and platelet-erythrocyte aggregates (PEAs) may play a role.

Purpose of the Study:

  • To investigate the role of CCCs in the immunothrombotic state of COVID-19.
  • To correlate CCC levels with clinical outcomes and explore their potential for microcirculatory obstruction.

Main Methods:

  • Analysis of 46 blood samples from 37 COVID-19 patients and 12 healthy controls using imaging flow cytometry.
  • Correlation analysis between CCC levels and clinical parameters.
  • In silico simulations to predict microcirculatory obstruction.

Main Results:

  • COVID-19 patients exhibited significantly higher levels of PEAs and PLAs compared to controls.
  • CLCs correlated with thrombotic complications, vasopressor need, acute kidney injury, and pneumonia.
  • PEAs were associated with positive bacterial cultures.
  • In silico models indicated CLCs can cause microcirculatory obstruction at low flow velocities and higher branching angles.

Conclusions:

  • Circulating cellular clusters, particularly CLCs, PLAs, and PEAs, are implicated in the pathophysiology of severe COVID-19.
  • These clusters may serve as potential biomarkers for adverse outcomes and therapeutic targets in inflammation-related thrombosis.

Keywords:
Cell biologyHealth sciencesImmunologyMicrobiology

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