Endothelial cells are not productively infected with SARS-CoV-2

First published: October 24, 2021 https://doi.org/10.1002/cti2.1350

Commentary

Thrombotic and microvascular complications were frequently seen in deaths in patients with COVID-19, but it remains controversial whether this is caused by direct viral infection of the endothelium or by inflammation-induced activation of the endothelium.

We showed that primary human endothelial cells express very low levels of the SARS-CoV-2 receptor ACE2 and the protease TMPRSS2, blocking their capacity for productive viral infection and limiting their ability to produce infectious virus.

Thus, our results indicate that endothelial cells can only become infected if they overexpress ACE2 or are exposed to very high concentrations of SARS-CoV-2.

They also showed that SARS-CoV-2 does not infect endothelial cells in 3D vessels under flow conditions, indicating that endothelial cells are not infected by SARS-CoV-2 in the co-culture model.

However, the endothelial cells sensed and responded to infection of adjacent epithelial cells, increasing ICAM-1 expression and releasing pro-inflammatory cytokines.

In summary, these data suggest that in vivo endothelial cells are unlikely to be infected with SARS-CoV-2 and that infection may only occur when adjacent lung epithelium is exposed or when high viral load is present in the blood.