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.