Lingli Zhou a,c , Zhenhua Xu a , Gianni M. Castiglione a , Uri S. Soiberman a , Charles G. Eberhart a,b,
Elia J. Duh a,
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
b Department of Pathology, Johns Hopkins University School of Medicine, USA
c State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
A B S T R A C T
Purpose: Conjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2
has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus.
The purpose of this study was to determine whether ocular surface cells possess the key factors required for
cellular susceptibility to SARS-CoV-2 entry/infection.
Methods: We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the
receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following
binding of the viral spike protein to ACE2.
Results: Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the con-
junctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal
epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithe-
lium, especially prominent in the superficial epithelium, as well as weak or focal expression in the substantia
propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, Western blot analysis of protein
lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and
TMPRSS2.
Conclusions: Together, these results suggest that ocular surface cells including conjunctiva are susceptible to
infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person
transmission of this virus. This highlights the importance of safety practices including face masks and ocular
contact precautions in preventing the spread of COVID-19 disease.