Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jul;10(7):976-986.
doi: 10.1002/sctm.20-0543. Epub 2021 Mar 12.

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

Lyle Armstrong  1 , Joseph Collin  1 , Islam Mostafa  1 , Rachel Queen  1 , Francisco C Figueiredo  1   2 , Majlinda Lako  1
Affiliations
Review

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

Lyle Armstrong et al. Stem Cells Transl Med. 2021 Jul.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in December 2019 and spread quickly causing the coronavirus disease 2019 (COVID-19) pandemic. Recent single cell RNA-Seq analyses have shown the presence of SARS-CoV-2 entry factors in the human corneal, limbal, and conjunctival superficial epithelium, leading to suggestions that the human ocular surface may serve as an additional entry gateway and infection hub for SARS-CoV-2. In this article, we review the ocular clinical presentations of COVID-19 and the features of the ocular surface that may underline the overall low ocular SARS-CoV-2 infection. We critically evaluate the studies performed in nonhuman primates, ex vivo organ culture ocular models, stem cell derived eye organoids and the differences in infection efficiency observed in different parts of human ocular surface epithelium. Finally, we highlight the additional work that needs to be carried out to understand the immune response of the ocular surface to SARS-CoV-2 infection, which can be translated into prophylactic treatments that may be applied to other organ systems.

Keywords: ACE2; COVID-19; SARS-CoV-2; TMPRSS2; conjunctiva; cornea; coronavirus; limbus; ocular surface; organ and animal models; scRNA-Seq; tears; therapy.

PubMed Disclaimer

Conflict of interest statement

The authors declared no potential conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Schematic presentation showing the viral entry and propagation into the host cell
FIGURE 2
FIGURE 2
Schematic presentation showing the ocular surface consisting of cornea, conjunctiva, and tear film on the left and tear film layers (superficial lipid layer, aqueous component, and mucins) on the right
FIGURE 3
FIGURE 3
Schematic showing potential SARS‐CoV‐2 entry into the eye via infection of ocular surface epithelium (left hand side panel) or the systemic routes (right hand side panel)
FIGURE 4
FIGURE 4
Expression of coronavirus‐associated receptors and factors in human ocular surface. Single cell RNA‐Seq of human cornea was performed and the expression of coronavirus‐associated receptors and factors was assessed and shown as dot plots. The size of the dots indicates the proportion of cells, while the color indicates the mean expression
See this image and copyright information in PMC

References

    1. Woolhouse M, Scott F, Hudson Z, Howey R, Chase‐Topping M. Human viruses: discovery and emeraence. Philos Trans R Soc B Biol Sci. 2012;367:2864‐2871. - PMC - PubMed
    1. De Wit E, Van Doremalen N, Falzarano D, et al. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016;14:523‐534. - PMC - PubMed
    1. Chan JFW, Lau SKP, To KKW, et al. Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS‐like disease. Clin Microbiol Rev. 2015;28:465‐522. - PMC - PubMed
    1. Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382:727‐733. - PMC - PubMed
    1. Chan JF‐W, Yuan S, Kok K‐H, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person‐to‐person transmission: a study of a family cluster. Lancet. 2020;395:514‐523. - PMC - PubMed

Publication types