Global gene expression profiling of circulating endothelial cells in SARS-CoV-2-infected cynomolgus macaques

Vascular disruption caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to elevated levels of circulating endothelial cells (CECs); however, the role of CECs in SARS-CoV-2 remains uncharacterized. Here, we analyzed transcriptional changes in CECs from SARS-CoV-2-infected cynomolgus macaques that could reflect the pathophysiology of patients with coronavirus disease 2019 (COVID-19). We found that genes involved in metabolic processes and dysregulated immune responses were upregulated in CECs upon infection with SARS-CoV-2 compared with uninfected controls. Notably, immunization with a recombinant SARS-CoV-2 spike glycoprotein (GBP 510) stimulates CEC-induced protective immunity, marked by enhanced T cell proliferation and reduced neutrophil migration, both of which have been shown to contribute to the pathogenesis of severe COVID-19. These data provide insight into the clinical significance of CECs and suggest a potential novel therapeutic strategy for COVID-19. RNA-seq profiling of CECs (CD31+CD45- cells) isolated in PBMCs from cynomolgus macaques before (0 dpi) and 7 d (7 dpi) after SARS-CoV-2 infection with (G)/without immunization ©