SARS-CoV-2 Infection of Ocular Cells from Human Adult Donor Eyes and hESC-Derived Eye Organoids
Abstract
The outbreak of COVID-19 caused by the SARS-CoV-2 virus has created an unparalleled
disruption of global behavior and a significant loss of human lives. To minimize SARS-CoV-2
spread, understanding the mechanisms of infection from all possible viral entry routes is
essential. As aerosol transmission is thought to be the primary route of spread, we sought to
investigate whether the eyes are potential entry portals for SARS-CoV-2. While virus has been
detected in the eye, in order for this mucosal membrane to be a bone fide entry source SARS-CoV-2
would need the capacity to productively infect ocular surface cells. As such, we
conducted RNA sequencing in ocular cells isolated from adult human cadaver donor eyes as well as
from a pluripotent stem cell-derived whole eye organoid model to evaluate the expression of ACE2
and TMPRSS2, essential proteins that mediate SARS-CoV-2 viral entry. We also infected eye
organoids and adult human ocular cells with SARS-CoV-2 and evaluated virus replication and the
host response to infection. We found the limbus was most susceptible to infection, whereas the
central cornea exhibited only low levels of replication. Transcriptional profiling of the limbus
upon SARS-CoV-2 infection, found that while type I or III interferons were not detected in the
lung epithelium, a significant inflammatory response was mounted. Together these data suggest
that the human eye can be directly infected by SARS-CoV-2 and thus is a route warranting
protection.
Funding: The National Eye Institute (NEI), Bethesda, MD, USA, extramural grant 1R21EY030215-01 and the Icahn School of Medicine at Mount Sinai supported this study.
Funding: The National Eye Institute (NEI), Bethesda, MD, USA, extramural grant 1R21EY030215-01 and the Icahn School of Medicine at Mount Sinai supported this study.