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Co-expression of SARS-CoV-2 entry genes in the superficial adult human conjunctival, limbal and corneal epithelium suggests an additional route of entry via the ocular surface

Lookup NU author(s): Dr Joseph Collin, Dr Rachel Queen, Dr Darin Zerti, Maria Georgiou, Ivo Djidrovski, Raf Hussain, Dr Jonathan Coxhead, Dr Steven Lisgo, Professor Francisco Figueiredo, Professor Lyle Armstrong, Professor Majlinda Lako

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Purpose: The high infection rate of SARS-CoV-2 necessitates the need for multiple studies identifying the molecular mechanisms that facilitate the viral entry and propagation. Currently the potential extra-respiratory transmission routes of SARS-CoV-2 remain unclear. Methods: Using single-cell RNA Seq and ATAC-Seq datasets and immunohistochemical analysis, we investigated SARS-CoV-2 tropism in the embryonic, fetal and adult human ocular surface. Results: The co-expression of ACE2 receptor and entry protease TMPRSS2 was detected in the human adult conjunctival, limbal and corneal epithelium, but not in the embryonic and fetal ocular surface up to 21 post conception weeks. These expression patterns were corroborated by the single cell ATAC-Seq data, which revealed a permissive chromatin in ACE2 and TMPRSS2 loci in the adult conjunctival, limbal and corneal epithelium. Co-expression of ACE2 and TMPRSS2 was strongly detected in the superficial limbal, corneal and conjunctival epithelium, implicating these as target entry cells for SARS-CoV-2 in the ocular surface. Strikingly, we also identified the key pro-inflammatory signals TNF, NFKβ and IFNG as upstream regulators of the transcriptional profile of ACE2+TMPRSS2+ cells in the superficial conjunctival epithelium, suggesting that SARS-CoV-2 may utilise inflammatory driven upregulation of ACE2 and TMPRSS2 expression to enhance infection in ocular surface. Conclusions: Together our data indicate that the human ocular surface epithelium provides an additional entry portal for SARS-CoV-2, which may exploit inflammatory driven upregulation of ACE2 and TMPRSS2 entry factors to enhance infection.


Publication metadata

Author(s): Collin J, Queen R, Zerti D, Dorgau B, Georgiou M, Djidrovski I, Hussain R, Coxhead JM, Joseph A, Rooney P, Lisgo S, Figueiredo FC, Armstrong L, Lako M

Publication type: Article

Publication status: Published

Journal: The Ocular Surface

Year: 2020

Pages: epub ahead of print

Online publication date: 03/06/2020

Acceptance date: 26/05/2020

Date deposited: 16/11/2020

ISSN (print): 1542-0124

ISSN (electronic): 1937-5913

Publisher: Elsevier

URL: https://doi.org/10.1016/j.jtos.2020.05.013

DOI: 10.1016/j.jtos.2020.05.013


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