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Review
. 2020 Sep 1;4(3):40.
doi: 10.3390/vision4030040.

Potential of Ocular Transmission of SARS-CoV-2: A Review

Brad P Barnett  1 , Karl Wahlin  2 , Michal Krawczyk  2 , Doran Spencer  2 , Derek Welsbie  2 , Natalie Afshari  2 , Daniel Chao  2
Affiliations
Review

Potential of Ocular Transmission of SARS-CoV-2: A Review

Brad P Barnett et al. Vision (Basel). .

Abstract

Purpose of review: to provide a prospective on the current mechanisms by which SARS-CoV-2 enters cells and replicates, and its implications for ocular transmission. The literature was analyzed to understand ocular transmission as well as molecular mechanisms by which SARS-CoV-2 enters cells and replicates. Analysis of gene expression profiles from available datasets, published immunohistochemistry, as well as current literature was reviewed, to assess the likelihood that ocular inoculation of SARS-CoV-2 results in systemic infection.

Recent findings: The ocular surface and retina have the necessary proteins, Transmembrane Serine Protease 2 (TMPRSS2), CD147, Angiotensin-Converting Enzyme 2 (ACE2) and Cathepsin L (CTSL) necessary to be infected with SARS-CoV-2. In addition to direct ocular infection, virus carried by tears through the nasolacrimal duct to nasal epithelium represent a means of ocular inoculation.

Summary: There is evidence that SARS-CoV-2 may either directly infect cells on the ocular surface, or virus can be carried by tears through the nasolacrimal duct to infect the nasal or gastrointestinal epithelium.

Keywords: COVID-19; SARS-CoV-2; conjunctivitis; coronavirus; ocular transmission.

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Conflict of interest statement

The authors do not have any relevant conflicts of interest.

Figures

Figure 1
Figure 1
SARS-COV-2 infection pathway. (1). SARS-CoV-2 has a spike glycoprotein that must first be cleaved by TMPRSS2. (2). Spike protein interacts with CD147 or Angiotensin Converting Enzyme 2 (ACE-2). (3). The virus is endocytosed and cathepsin L (CTSL) must further cleave the virus. (4). The virus fuses with the endosome membrane, thereby releasing single stranded RNA (ssRNA) into the cytosol.
Figure 2
Figure 2
Structures at risk of infection from ocular exposure of SARS-CoV-2. Two potential pathways by which ocular exposure could lead to transmission of the SARS-CoV-2 virus include direct infection of ocular tissues as well as infection of nasal or gastrointestinal epithelium due to virus carried by tears through the nasolacrimal duct.
Figure 3
Figure 3
Gene expression of TMPRSS2, CD147, ACE-2 and CTSL. Graph of relative global gene expression in ocular and non-ocular tissue. TMPRSS2, CD147, ACE-2 and CTSL are all expressed in ocular tissues and non-ocular tissues that are currently accepted as sites for SARS-CoV-2 infection.
Figure 4
Figure 4
Relative expression of TMPRSS2, CD147, ACE-2 and CTSL in ocular structures. The figure summarizes data available from immunohistochemistry and gene expression profiles. (-) No expression, (+) Low expression, (+) Moderate expression, (+) High Expression.
Figure 5
Figure 5
Forest plot showing the association of eye protection with risk of MERS, SARS-CoV-1 (SARS) and SARS-CoV-2 (COVID-19). The plot diagram represents unadjusted estimates. MERS = Middle East respiratory syndrome. SARS = severe acute respiratory syndrome. RR = relative risk. aOR = adjusted odds ratio. aRR = adjusted relative risk [53].
Figure 6
Figure 6
Potential topical ocular medications targeting specifically TMPRSS2, ACE-2, CD147 and CTSL.
See this image and copyright information in PMC

References

    1. Peiris J.S., Yuen K.Y., Osterhaus A.D., Stohr K. The severe acute respiratory syndrome. N. Engl. J. Med. 2003;349:2431–2441. doi: 10.1056/NEJMra032498. - DOI - PubMed
    1. Raboud J., Shigayeva A., McGeer A., Bontovics E., Chapman M., Gravel D., Henry B., Lapinsky S., Loeb M., McDonald L.C., et al. Risk factors for SARS transmission from patients requiring intubation: A multicentre investigation in Toronto, Canada. PLoS ONE. 2010;5:e10717. doi: 10.1371/journal.pone.0010717. - DOI - PMC - PubMed
    1. Sungnak W., Huang N., Becavin C., Berg M., Queen R., Litvinukova M., Talavera-Lopez C., Maatz H., Reichart D., Sampaziotis F., et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat. Med. 2020;26:681–687. doi: 10.1038/s41591-020-0868-6. - DOI - PMC - PubMed
    1. Kim J.H., Chun Y.S., Lee S.H., Mun S.K., Jung H.S., Lee S.H., Son Y., Kim J.C. Ocular surface reconstruction with autologous nasal mucosa in cicatricial ocular surface disease. Am. J. Ophthalmol. 2010;149:45–53. doi: 10.1016/j.ajo.2009.07.030. - DOI - PubMed
    1. Leonardi A., Rosani U., Brun P. Ocular Surface Expression of SARS-CoV-2 Receptors. Ocul. Immunol. Inflamm. 2020;28:735–738. doi: 10.1080/09273948.2020.1772314. - DOI - PubMed