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Neutrophil adhesion to vessel walls impairs pulmonary circulation in COVID-19 pathology

Hiroshi Ueki1,2, I-Hsuan Wang3, Maki Kiso4

  • 1Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. h-ueki@ims.u-tokyo.ac.jp.

Nature Communications
|January 13, 2025
PubMed

Insights

Severe COVID-19 involves neutrophil adhesion to lung vessels, causing microthrombi and impaired blood flow. This study reveals how neutrophil behavior contributes to COVID-19 severity and lung perfusion defects.

Area of Science:

  • Pulmonary medicine
  • Immunology
  • Virology

Background:

  • Microthrombus formation correlates with COVID-19 severity.
  • The precise mechanisms underlying this association are not fully understood.

Purpose of the Study:

  • To elucidate the role of neutrophil adhesion and microthrombus formation in SARS-CoV-2-induced pneumonia.
  • To investigate the in vivo mechanisms contributing to COVID-19 severity.

Main Methods:

  • Utilized an in vivo two-photon imaging system in mouse models of severe pneumonia caused by SARS-CoV-2 infection.
  • Analyzed scRNA-seq data from peripheral blood mononuclear cells of COVID-19 patients.

Main Results:

  • SARS-CoV-2 infection increased expression of adhesion molecules on intravascular neutrophils in mouse lungs.
  • Prolonged neutrophil adhesion led to platelet aggregation and impaired lung perfusion.
  • Elevated CD44 and SELL expression in neutrophils of severe COVID-19 patients was observed, consistent with mouse model findings.

Conclusions:

  • Pulmonary perfusion defects, driven by neutrophil adhesion to pulmonary vessels, are a significant contributor to COVID-19 severity.
  • Neutrophil-mediated microthrombus formation plays a critical role in the pathophysiology of severe COVID-19.

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