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

  • Funded by UK Research and Innovation (UKRI)
  • Total publications:12 publications

Grant number: BB/V01126X/1

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Key facts

  • Disease

    COVID-19
  • Known Financial Commitments (USD)

    $249,480.84
  • Funder

    UK Research and Innovation (UKRI)
  • Principle Investigator

    Pending
  • Research Location

    United Kingdom, Europe
  • Lead Research Institution

    Newcastle University
  • Research Category

    Pathogen: natural history, transmission and diagnostics

  • Research Subcategory

    Pathogen morphology, shedding & natural history

  • Special Interest Tags

    Gender

  • Study Subject

    Non-Clinical

  • Clinical Trial Details

    N/A

  • Broad Policy Alignment

    Pending

  • Age Group

    Not Applicable

  • Vulnerable Population

    Not applicable

  • Occupations of Interest

    Not applicable

Abstract

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.

Publicationslinked via Europe PMC

Last Updated:38 minutes ago

View all publications at Europe PMC

Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell Transplantation.

Conjunctival epithelial cells resist productive SARS-CoV-2 infection.

Direct transcriptomic comparison of xenobiotic metabolism and toxicity pathway induction of airway epithelium models at an air-liquid interface generated from induced pluripotent stem cells and primary bronchial epithelial cells.

Pathophysiology of aniridia-associated keratopathy: Developmental aspects and unanswered questions.

SARS-CoV-2 infects an upper airway model derived from induced pluripotent stem cells.

Referral Patterns of Patients with Limbal Stem Cell Deficiency to a Specialized Tertiary Center in the United Kingdom.

In the eye of the storm: SARS-CoV-2 infection and replication at the ocular surface?

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.

A single cell atlas of human cornea that defines its development, limbal progenitor cells and their interactions with the immune cells.