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.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative virus of COVID-19 (coronavirus disease 2019) and is transmitted via droplets/aerosols containing the virus. SARS-CoV-2 invasion of the lung is initiated by the binding of the virus to the alveolar epithelium using angiotensin-converting enzyme-2 (ACE-2) as a receptor1,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 2" title="Lan, J. et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound