Assessing SARS-CoV-2 entry, replication and prevention in a primary human conjunctival cell model and organ cultured cornea/conjunctiva.

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The SARS-CoV-2 virus, which has caused the COVID-19 pandemic, is highly infectious and predominantly transmitted through respiratory droplets. To enter the host cell SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a cellular receptor and the transmembrane protease serine type 2 (TMPRSS2) for fusion of viral and cellular membranes. The ocular surface epithelia, conjunctiva and cornea, represent an additional mucosal surface, which can be exposed to respiratory droplets. Several published reports have shown that SARS-CoV-2 can cause conjunctivitis, either as an early sign of infection, or during hospitalization for severe COVID-19 disease. In a recent study of 38 COVID-19 patients, 31.6% had conjunctivitis with 16.7% of these testing positive for SARS-CoV-2 from conjunctival and nasopharyngeal swabs. There is evidence that numerous properties allow the eye to serve as a potential site of virus replication and a gateway for the establishment of respiratory infection, through the nasolacrimal system linking the ocular and respiratory tissues. Our recent data shows co-expression of ACE2 and TMPRSS2 in human superficial conjunctival, limbal and corneal epithelium, suggesting a potential extra-respiratory transmission route of SARS-CoV-2 via the ocular surface. In this proposal we will use human ex vivo differentiated conjunctival and corneal epithelium and organ cultured cornea/conjunctiva as pre-clinical tools to study the entry of SARS-CoV-2 via the ocular surface and to develop effective diagnostic, prophylactics and treatments in the fight against COVID-19. We envisage that proof-of-concept studies developed herein will lead not only to development of eye drops, but also nasal sprays and mouth washes, to provide the much-needed therapies in time of pandemics.