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

• Published in: Nature communications Vol. 16; no. 1; pp. 455 - 17
• Main Authors: Ueki, Hiroshi, Wang, I-Hsuan, Kiso, Maki, Horie, Kenta, Iida, Shun, Mine, Sohtaro, Ujie, Michiko, Hsu, Hung-Wei, Wu, Chen-Hui Henry, Imai, Masaki, Suzuki, Tadaki, Kamitani, Wataru, Kawakami, Eiryo, Kawaoka, Yoshihiro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.01.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 13/51; 14/34; 14/69; 45/91; 59; 631/326/596/4130; 64/60; 692/420/254; Adhesion; Animal models; Animals; Blood levels; CD44 antigen; Cell Adhesion; Cell adhesion molecules; COVID-19; COVID-19 - pathology; COVID-19 - physiopathology; COVID-19 - virology; Disease Models, Animal; Female; Humanities and Social Sciences; Humans; Hyaluronan Receptors - metabolism; Imaging techniques; In vivo methods and tests; Leukocytes (mononuclear); Leukocytes (neutrophilic); Lung - blood supply; Lung - pathology; Lungs; Male; Mice; Mice, Inbred C57BL; multidisciplinary; Neutrophils; Neutrophils - metabolism; Neutrophils - pathology; Perfusion; Peripheral blood mononuclear cells; Photons; Platelet Aggregation; Platelets; Pulmonary circulation; Pulmonary Circulation - physiology; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-55272-0

Microthrombus formation is associated with COVID-19 severity; however, the detailed mechanism remains unclear. In this study, we investigated mouse models with severe pneumonia caused by SARS-CoV-2 infection by using our in vivo two-photon imaging system. In the lungs of SARS-CoV-2-infected mice, increased expression of adhesion molecules in intravascular neutrophils prolonged adhesion time to the vessel wall, resulting in platelet aggregation and impaired lung perfusion. Re-analysis of scRNA-seq data from peripheral blood mononuclear cells from COVID-19 cases revealed increased expression levels of CD44 and SELL in neutrophils in severe COVID-19 cases compared to a healthy group, consistent with our observations in the mouse model. These findings suggest that pulmonary perfusion defects caused by neutrophil adhesion to pulmonary vessels contribute to COVID-19 severity. COVID-19 severity is linked to microthrombus formation. Here, using an in vivo two-photon imaging technique in mice and human scRNA-Seq data, the authors show increased adhesion molecules on vascular neutrophils leading to platelet aggregation and reduced lung perfusion.