SARS-CoV-2 apparently does not penetrate the cornea, unlike the herpes simplex virus 1 (HSV-1) and the Zika virus (ZIKV). This finding comes from a study conducted at the Washington University School of Medicine in St. Louis, Missouri.1
Given the paucity of data regarding airborne or droplet transmission of SARS-CoV-2 through the eye, the new findings are “somewhat reassuring,” said Rajendra S. Apte, MD, PhD. “We should be comforted that the corneal surface seems to be innately resistant to SARS-CoV-2 viral penetration.” He stressed, however, that further study is needed.
Study design. The study researchers pursued two lines of inquiry: 1) to evaluate the three viruses in human and/or animal models and 2) to explore the ability of interferon lambda (IFN-λ) to inhibit viral replication in the eye. This was done by blocking its action to determine whether virus proliferated. (Although IFN-λ and its receptor IFNlR1 are known to restrict viral replication in other barrier surfaces, this is the first study to describe their activity in the human eye.)
Good news with SARS-CoV-2. Results showed that SARS-CoV-2 did not penetrate the human cornea. In addition, the virus was not affected by IFN-λ. Specifically, no evidence was found of SARS-CoV-2 replication in seven donor samples inoculated with the virus in the presence of the anti–IFN-λ antibody.
As the researchers wrote, “… blockade of IFNlR1 did not make the human corneal tissue more permissive to infection with SARS-CoV-2.”1
Results with ZIKV. Working with genetically modified mice that had been inoculated with ZIKV, the researchers found ZIKV in the harvested and dissected murine corneas and other organs of the mice. Moreover, once the washed murine donor corneas were transplanted into naïve mice, ZIKV was still evident at low levels in all recipient animals, and one mouse had severe infection in multiple organs.
In human donor samples, ZIKV replicated only once out of three attempts, suggesting that the human cornea is somewhat resistant to ZIKV infection. Histological analysis revealed that ZIKV infected a small number of corneal epithelial cells, but the virus did not substantially penetrate into deeper layers.
“We were quite concerned during the Zika pandemic that viruses such as these [e.g., flaviviruses] could be transmitted by tissue transplantation,” Dr. Apte said. “It was reassuring to see low rates of transmission [in human tissue], given that transmission of viruses by solid organ transplantation is a major clinical concern.”
The researchers also tested whether IFN-λ protects against infection with ZIKV, using an anti-IFNlR1 antibody. The results indicate that blockade of IFN-λ enhances replication of ZIKV.
Results with HSV-1. Within 72 hours of infection with HSV-1, viral levels in the human cornea increased approximately 10-fold in the presence of the anti-IFNlR1 antibody. This blockade of IFN-λ led to more severe HSV-1 infection, suggesting that IFN-λ signaling in the cornea mediates protections against herpesvirus infection. The finding could pave the way for creation of interferon lambda–based therapeutics that can prevent or limit viral infection and any related vision loss, Dr. Apte said.
Making sense of the findings. Although receptors of SARS-CoV-2 are expressed on the corneal and conjunctival surfaces, the coronavirus does not seem to be able to penetrate the cornea and replicate within this tissue, Dr. Apte said. “This result suggests some other resistance factor in the cornea, other than interferon lambda, that prevents corneal infection from SARS-CoV-2,” he added.
Dr. Apte cautioned that these preliminary data do not definitively prove that the eye is not a route for entry of the virus. “But it is interesting that the cornea does not support SARS-CoV-2 viral infection and replication in the laboratory,” he said. Given the likelihood of future pandemics and epidemics, he added that “understanding how antiviral barrier immunity works will be critically important to our ability to fight these infections.”
1 Miner JJ et al. Cell Rep. 2020;33(5):108339.
Relevant financial disclosures—Dr. Apte: None.
For full disclosures and the disclosure key, see below.
Full Financial Disclosures
Dr. Apte EdenRoc Life Sciences: O; Genentech: C; Iveric bio: O; Liberty Biosecurity: C,O; Merck: C; Metro Biotech International: O; Metro International: O,P; Mylan: C; Novartis/Alcon: C; Ribomic: C.
Dr. Lee None.
Dr. Petrova None.
Dr. Woo Abbvie: L; Allergan: L; Alteogen: C,S; Bayer: L; Curacle: C,S; Novartis/Alcon: C,L,S; Novelty Nobility: C,S; Panolos Bioscience: C; Philophos: C; Retimark: O; Samsung Bioepis: C,S; SCAI Therapeutics: L.; Taejoon: L.
||Consultant fee, paid advisory boards, or fees for attending a meeting.
||Employed by a commercial company.
||Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
||Equity ownership/stock options in publicly or privately traded firms, excluding mutual funds.
||Patents and/or royalties for intellectual property.
||Grant support or other financial support to the investigator from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and/or pharmaceutical companies.
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