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  • By Ashiyana Nariani, MD, MPH; Rishabh Jain
    Comprehensive Ophthalmology, Cornea/External Disease

    The authors assessed whether the human ocular surface epithelium could serve as an entry portal for SARS-CoV-2. 

    Study design

    SARS-CoV-2 uses the angiotensin converting enzyme 2 (ACE2) as a receptor for cell entry, with transmembrane protease serine type 2 (TMPRSS2) responsible for cleaving the spike protein to fuse viral and cell membranes. Single cell RNA sequencing, ATAC-Seq datasets, immunohistochemical analysis and protein quantification techniques were used to analyze expression of these genes in adult and fetal/embryonic cornea-conjunctival tissues.


    ACE2 receptor and entry protease TMPRSS2 RNA were coexpressed in human adult conjunctival, limbal and corneal epithelium, but not in corresponding embryonic and fetal tissues up to 21 weeks post-conception. A similar trend was observed in the chromatin accessibility of ACE2 and TMPRSS2 loci in the adult conjunctival, limbal and corneal epithelium, as determined by ATAC-Seq. Furthermore, the upstream upregulation of ACE2 and TMPRSS2 in superficial conjunctival epithelial cells by several critical pro-inflammatory signals (TNF-α, NFK-β and IFN-γ) suggests that SARS-CoV-2 may capitalize on the host’s inflammatory immune response to enhance infectivity in ocular surface tissues.


    Adult tissue samples were obtained from only 4 human donors between 51 and 86 years old. Additionally, human bulk RNA-Seq data for all entry genes obtained from the conjunctiva of children 2 to 7 years old was not compared to adult or fetal conjunctiva samples used in this study.

    Clinical significance

    Differences in adult and fetal expression profiles corroborate clinical observations of low symptomaticity and mortality in children infected with SARS-CoV-2. Given that viral RNA has been detected in ocular swabs of COVID-positive patients, prophylactic eye drops should be explored as a means to stop viral entry through the conjunctival, limbal and corneal epithelium. Moreover, a growing body of evidence indicates that the human ocular surface presents not only a site of COVID infection but also an extra-respiratory route of COVID transmission, suggesting the need for protective eye equipment for all health professionals, particularly ophthalmologists who may be exposed to ocular transmission from asymptomatic patients.