As researchers continue to ferret out new potential symptoms and modes of transmission for COVID-19, a new study from Johns Hopkins University suggests the ocular surface is susceptible to infection and could serve as a portal of entry via exposure to aerosolized droplets or hand-eye contact. The researchers also claim the eye could act as a reservoir for person-to-person transmission, which underscores the importance of safety practices, including face masks, and ocular contact precautions to prevent the disease’s spread.1

The investigation, which the outlet bioRxiv published online prior to peer review, reports that the key cell surface receptor for COVID-19 (called ACE2), which  binds to its viral spike protein, is expressed on human eyes. This makes them susceptible to COVID-19. The researchers also purport the eyes and conjunctivas used in their study expressed TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2.1

“The diffuse expression of ACE2 and TMPRSS2 on the ocular surface of multiple specimens is quite striking and supports the concept that it can be infected by SARS-CoV-2,” says researcher and ophthalmic pathologist Charles Eberhart, MD, PhD, of Johns Hopkins University.

The team from Johns Hopkins analyzed 10 human post-mortem eyes as well as specimens collected from surgeries for the expression of ACE2 and TMPRSS2. None of the specimens were from people with diagnosed with COVID-19.1

Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, 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 epithelium, particularly in the superficial epithelium and substantia propria. All eye and conjunctival specimens also expressed TMPRSS2.1

The investigators also conducted western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery that confirmed expression of ACE2 and TMPRSS2.1

The susceptibility of the conjunctiva to infection with SARS-CoV-2 provides further context for published clinical studies, the researchers said. COVID-19 is often associated with conjunctival manifestations including conjunctivitis, which was present in about 30% of one clinical study of COVID-19, they added.2

The presence of ACE2 and TMPRSS2 in conjunctival and corneal epithelial cells supports the theory that the ocular surface could be a secondary site of infection following the respiratory tract or possibly even as the initial entry point, the investigators noted. Infection of ocular surface cells could lead to the eye being an important carrier, with ocular virus shedding constituting a significant mechanism for infection of other individuals, they added.1

The study also highlighted the importance of safety practices in the general community to prevent infection and spread such as proper hygiene, wearing face masks and the need for extra caution among eye care practitioners.1

bioRxiv reminds readers that these are preliminary reports that have yet to go through a peer review process; thus, clinicians should not consider the information as conclusive, nor should it guide clinical practice/health-related behavior.3

1. Zhou L, Xu Z, Castiglione GM, et al. ACE2 and TMPRSS2 are expressed on the human ocular surface, suggesting susceptibility to SARS-CoV-2 infection. bioRxiv. May 9, 2020 [Epub, ahead of print].

2. Wu P, Duan F, Luo C, et al. Characteristics of ocular findings of patients with

coronavirus disease 2019 (COVID-19) in Hubei Province, China. JAMA Ophthalmol. March 31, 2020. [Epub ahead of print].

3. COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv. bioRxiv. Accessed May 19, 2020.