Covid-19 and Eyes: what we know about the role of ocular tissue in the transmission of the virus
Eyes represent an important gateway for infection of Covid-19 that should not be underestimated.
COVID-19 is the name which has been proposed by the World Health Organization, for the "Severe Acute Respiratory Syndrome coronavirus 2" (SARS-CoV-2). This name derives from the Latin word corona, which means crown; due to the characteristic structure of the virus surface projections, on the viral envelope.
Covid-19 has been known to manifest in other regions apart from the respiratory tract, including the gastrointestinal tract and ocular tissues. However, most of the research on Covid focuses on the respiratory tract, due to its life-threatening nature.
Despite this, the manifestations of Covid-19 in other organ systems should not be ignored, as they can represent an alternative mode of transmission. In early January, for example, Dr Li Wenliang, an Ophthalmologist at Wuhan Central Hospital, contracted COVID-19 from an asymptomatic glaucoma patient and succumbed to the disease one month later.
Anecdotal reports suggested that where no eye protection was worn, the virus could have been transmitted by aerosol contact with the conjunctiva, and cause infection. Conjunctivitis could be the first presenting symptom of COVID-19, before the appearance of other symptoms such as cough and fever.
In 2004, toward the end of the SARS-CoV crisis, a new human coronavirus was identified: HCoV-NL63. The virus was first isolated from a 7-month-old child before being identified in seven additional individuals. During the infection, the child had symptoms and physical examination findings of bronchiolitis and conjunctivitis.
In 2005, a retrospective study that analyzed the nasal swabs of children with respiratory illnesses, from 2000 to 2003 for HCoV-NL63 was conducted in France: they found that 17% (n = 3) of HCoV-NL63 patients (n = 18) had developed conjunctivitis.
Various published case series highlighted the presence of SARS-CoV RNA in tears. However to date, it is still unclear how SARS-CoV is present in tears.
Proposed theories include the conjunctiva being the direct inoculation site of SARS-CoV from infected droplets, the migration of upper respiratory tract infection through the nasolacrimal duct or even hematogenous infection of the lacrimal gland. A study that assessed both tears and conjunctival scrapings from 17 patients with confirmed SARS-CoV infection did not yield any positive result from RT-PCR.
In another recent case series including 38 patients with COVID-19 from Hubei province (China), 12 patients had ocular manifestations, such as epiphora, conjunctival congestion, or chemosis, and these symptoms commonly occurred in patients with more severe systemic manifestations.
In 28 nasopharyngeal swabs, and 2 conjunctival swabs reverse transcriptase-polymerase chain reaction results were positive for severe acute respiratory syndrome coronavirus 2, and more significant changes in blood test values appeared in patients with ocular abnormalities.
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Genomic and structural analyses showed that the SARS-CoV-2 has a similar receptor-binding motif as SARS-CoV, which allows it to infect host cells via the angiotensin-converting-enzyme-2 (ACE2). The expression of ACE2 in anterior tissues such as the conjunctiva or cornea has yet to be established.
However, interestingly, the renin-angiotensin system (RAS), apart from its well-known endocrine role in blood pressure regulation, also has complicated autocrine functions within specific tissues. The human eye has its own intraocular Renin-Angiotensin system, that has been the interest of many projects focusing on developing anti-glaucomatous drugs. ACE2 has been found in fact in the aqueous humour.
Given the anecdotal nature of evidence regarding SARSCoV- 2 transmission through ocular tissue, more research has to be done to confirm its ability to infect ocular tissue and its pathogenic mechanisms.
As the current epidemic continues, a better understanding of the virus will emerge, hopefully with more emphasis on research into the relationship between human Covid-19 and the eye. This understanding will help not only to guide infection control measures but can also provide insights on the feasibility of using ocular tissues or even tears as a medium of diagnosis.
Bibliography:
• Tracy H. T. Lai, Emily W. H. Tang, Sandy K. Y. Chau, Kitty S. C. Fung & Kenneth K. W. Li Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong; Graefe's Archive for Clinical and Experimental Ophthalmology doi: 00417-020-04641-8
• W. Guan, Z. Ni, Yu Hu, W. Liang, C. Ou, J. He, L. Liu, H. Shan, C. Lei, D.S.C. Hui, B. Du, L. Li, G. Zeng, K.-Y. Yuen, R. Chen, C. Tang, T. Wang, P. Chen, J. Xiang, S. Li, Jin-lin Wang, Z. Liang, Y. Peng, L. Wei, Y. Liu, Ya-hua Hu, P. Peng, Jian-ming Wang, J. Liu, Z. Chen, G. Li, Z. Zheng, S. Qiu, J. Luo, C. Ye, S. Zhu, and N. Zhong, for the China Medical Treatment Expert Group for Covid-19; Clinical Characteristics of Coronavirus Disease 2019 in China; The New England Journal of Medicine, February 28, 2020
• Ivan Seah, MBBS a and Rupesh Agrawal, Can the Coronavirus Disease 2019 (COVID-19) Affect the Eyes? A Review of Coronaviruses and Ocular Implications in Humans and Animals. Ocular Immunology And Inflammation, 2020 https://doi.org/10.1080/09273948.2020.1738501
• PingWu; Fang Duan; Chunhua Luo; Qiang Liu; Xingguang Qu, Liang Liang, Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China; JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2020.1291, Published online March 31, 2020.