SARS-CoV-2 infects human adult donor eyes and hESC-derived ocular epithelium

Anne Z. Eriksen, Rasmus Møller, Bar Makovoz, Skyler A. Uhl, Benjamin R. tenOever*, Timothy A. Blenkinsop

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The SARS-CoV-2 pandemic has caused unparalleled disruption of global behavior and significant loss of life. To minimize SARS-CoV-2 spread, understanding the mechanisms of infection from all possible routes of entry is essential. While aerosol transmission is thought to be the primary route of spread, viral particles have been detected in ocular fluid, suggesting that the eye may be a vulnerable point of viral entry. To this end, we confirmed SARS-CoV-2 entry factor and antigen expression in post-mortem COVID-19 patient ocular surface tissue and observed productive viral replication in cadaver samples and eye organoid cultures, most notably in limbal regions. Transcriptional analysis of ex vivo infected ocular surface cells and hESC-derived eye cultures revealed robust induction of NF-κB in infected cells as well as diminished type I/III interferon signaling. Together these data suggest that the eye can be directly infected by SARS-CoV-2 and implicate limbus as a portal for viral entry.

Original languageEnglish
JournalCell Stem Cell
Volume28
Issue number7
Pages (from-to)1205-1220
ISSN1934-5909
DOIs
Publication statusPublished - 2021

Bibliographical note

Funding Information:
We would like to thank the patients and families who generously donated for the research conducted. We would like to thank the Eye Bank for Sight Restoration for their continual support and hard work at procuring donations. We would like to thank Dr. Barbara Corneo for manuscript review. This work was supported in part by a Challenge Grant award from Research to Prevent Blindness , the National Eye Institute (NEI), extramural grant 1R21EY030215-01 , and the Icahn School of Medicine at Mount Sinai . We would like to thank the Carlsberg Foundation and the Lundbeck Foundation for supporting this work.

Keywords

  • ACE2
  • Cornea
  • COVID-19
  • Eye
  • Interferon
  • Limbus
  • NF-κB
  • SARS-CoV-2
  • scRNA-seq
  • Stem cells

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