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

Collin, Joseph; Queen, Rachel; Zerti, Darin; Dorgau, Birthe; Γεωργίου, Μαρία; Djidrovski, Ivo; Hussain, Rafiqul; Coxhead, Jonathan; Joseph, Agatha; Rooney, Paul; Lisgo, Steven; Figueiredo, Francisco C; Armstrong, Lyle; Lako, Majlinda

doi:10.1016/j.jtos.2020.05.013

Cited by 127 publications

(163 citation statements)

References 27 publications

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“…It has been widely speculated that SARS-CoV-2 may infect the eye ( Xia et al., 2020 ), although it is unusual for patients with SARS-CoV-2 to develop ocular symptoms. The possibility of corneal infection is supported by the fact that ACE2, a receptor for SARS-CoV-2, is highly expressed in the human corneal epithelium ( Collin et al., 2020 ; Zhou et al., 2020 ). Therefore, we tested whether a clinical isolate of SARS-CoV-2 could replicate in human corneal tissue.…”

Section: Resultsmentioning

confidence: 99%

HSV-1 and Zika Virus but Not SARS-CoV-2 Replicate in the Human Cornea and Are Restricted by Corneal Type III Interferon

et al. 2020

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Here, we report our studies of immune-mediated regulation of Zika virus (ZIKV), herpes simplex virus 1 (HSV-1), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the human cornea. We find that ZIKV can be transmitted via corneal transplantation in mice. However, in human corneal explants, we report that ZIKV does not replicate efficiently and that SARS-CoV-2 does not replicate at all. Additionally, we demonstrate that type III interferon (IFN-λ) and its receptor (IFNλR1) are expressed in the corneal epithelium. Treatment of human corneal explants with IFN-λ, and treatment of mice with IFN-λ eye drops, upregulates antiviral interferon-stimulated genes. In human corneal explants, blockade of IFNλR1 enhances replication of ZIKV and HSV-1 but not SARS-CoV-2. In addition to an antiviral role for IFNλR1 in the cornea, our results suggest that the human cornea does not support SARS-CoV-2 infection despite expression of ACE2, a SARS-CoV-2 receptor, in the human corneal epithelium.

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Section: Resultsmentioning

confidence: 99%

HSV-1 and Zika Virus but Not SARS-CoV-2 Replicate in the Human Cornea and Are Restricted by Corneal Type III Interferon

et al. 2020

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“…In the context of the route of administration, it has been proposed that the virus travels via direct airborne transmission since the entire ocular surface including the anterior cornea, tear film and conjunctiva communicates with air, similar to the nasal mucosa. Another proposed path of infiltration is the nasolacrimal route, facilitating the transport of viral particles from the respiratory tract to the ocular surface or vice versa [ 18 ]. These potential routes of infiltration may justify reports suggesting that SARS-CoV-2 causes conjunctivitis in COVID-19 positive patients [ [4] , [5] , [6] , 9 , 10 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of SARS-CoV-2 in human post-mortem ocular tissues

Sawant¹,

et al. 2021

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Background SARS-CoV-2 is found in conjunctival swabs and tears of COVID-19 patients. However, the presence of SARS-CoV-2 has not been detected in the human eye to date. We undertook this study to analyze the prevalence of SARS-CoV-2 in human post-mortem ocular tissues. Methods The expression of SARS-CoV-2 RNA was assessed by RT-PCR in corneal and scleral tissues from 33 surgical-intended donors who were eliminated from a surgical use per Eye Bank Association of America (EBAA) donor screening guidelines or medical director review or positive COVID-19 test. Ocular levels of SARS-CoV-2 RNA (RT-PCR), Envelope and Spike proteins (immunohistochemistry) and anti -SARS-CoV-2 IgG and IgM antibodies (ELISA) in blood were evaluated in 10 COVID-19 donors. Findings Of 132 ocular tissues from 33 surgical-intended donors, the positivity rate for SARS-CoV-2 RNA was ∼13% (17/132). Of 10 COVID-19 donors, six had PCR positive post-mortem nasopharyngeal swabs whereas eight exhibited positive post-mortem anti -SARS-CoV-2 IgG levels. Among 20 eyes recovered from 10 COVID-19 donors: three conjunctival, one anterior corneal, five posterior corneal, and three vitreous swabs tested positive for SARS-CoV-2 RNA. SARS-CoV-2 spike and envelope proteins were detected in epithelial layer of the corneas that were procured without Povidone-Iodine (PVP–I) disinfection. Interpretations Our study showed a small but noteworthy prevalence of SARS-CoV-2 in ocular tissues from COVID-19 donors. These findings underscore the criticality of donor screening guidelines, post-mortem nasopharyngeal PCR testing and PVP-I disinfection protocol to eliminate any tissue harboring SARS-CoV-2 being used for corneal transplantation.

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“…Inflammation milieu could potentiate upregulation of ACE-2 and TMPRSS2. 29 As the virus may replicate after the ocular surface is being infected by the SARS-CoV-2, the virus can cause ocular manifestation prior to any systemic symptoms. Although most of the ocular manifestation being reported was associated with red eyes, a case report by Hu et al 17 found that SARS-CoV-2 could be found in tears of asymptomatic eyes.…”

Section: Discussionmentioning

confidence: 99%

Are eyes the windows to COVID-19? Systematic review and meta-analysis

et al. 2020

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ObjectiveTo review and critically appraise the ocular manifestation and the presence of SARS-CoV-2 through PCR positivity from ocular samples in COVID-19-related patients. Moreover, to evaluate the time and severity association of ocular manifestation to systemic disease of COVID-19.Methods and analysisA systematic literature search from PubMed, ScienceDirect and Google Scholar databases was performed using standardised Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Selected keywords were related to COVID-19, ocular manifestation and PCR testing of SARS-CoV-2. Studies were assessed for their validity, and the data were extracted by two independent reviewers. Observational, case series and case report studies were included if they met the selection criteria. Meta-analysis was performed to estimate the pooled prevalence of ocular manifestations and PCR positivity from tears.ResultsThirty-one articles were qualitatively reviewed, and 14 studies were included in the meta-analysis. The pooled prevalence of ocular manifestation among COVID-19-related patients was 0.05 (95% CI 0.02% to 0.08). The overall PCR from tears samples positivity rate from COVID-19-related patients presenting with ocular manifestation was 0.38 (95% CI 0.14% to 0.65). Ocular manifestation could precede systemic manifestation in about 0.28 (95% CI 0.05% to 0.58) of COVID-19-related patients with ocular manifestations. Besides, ocular manifestation was not associated with a severe form of COVID-19.ConclusionAlthough the overall number of ocular manifestation and SARS-CoV-2 PCR positivity rate from ocular samples was very low, around a quarter of COVID-19-related patients with ocular manifestation presented their ocular manifestation earlier than the systemic manifestation regardless of the severity. Interestingly, SARS-CoV-2 PCR was positive from one-third of ocular samples, which could potentially be the source of infection to the respiratory tract and the environment, although the infectivity is yet to be determined.

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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

Cited by 127 publications

References 27 publications

HSV-1 and Zika Virus but Not SARS-CoV-2 Replicate in the Human Cornea and Are Restricted by Corneal Type III Interferon

HSV-1 and Zika Virus but Not SARS-CoV-2 Replicate in the Human Cornea and Are Restricted by Corneal Type III Interferon

Prevalence of SARS-CoV-2 in human post-mortem ocular tissues

Are eyes the windows to COVID-19? Systematic review and meta-analysis

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