SARS-CoV-2 infects ocular tissue, but surprisingly, inflammation was absent in the eyes of patients who died from COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), infects tissues throughout the human body, including the eye. The objective of this study was to evaluate changes and investigate cellular localization of SARS-CoV-2 in ocular tissues at autopsy. Investigators found a marked absence of inflammation despite evidence of SARS-CoV-2 infection in the eye, contrary to what is observed in other viral eye infections. The resultsopens in new tab/window appear in The American Journal of Pathologyopens in new tab/window, published by Elsevier.

Ophthalmic manifestations and tissue tropism of SARS-CoV-2 have been reported in association with COVID-19, but the pathology and cellular localization of SARS-CoV-2 have not yet been well characterized.

Lead investigator Daniel S. Chertow, MD, MPH, Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, and Laboratory of Virology, National Institute of Allergy and Infectious Diseases, explains, “The eye is an immune-privileged site and so may serve as a location for viral infection and persistence. We therefore sought to determine if eye tissues become infected with SARS-CoV-2, and if they do, what damage might be associated with this infection.”

Investigators evaluated eyes from 25 patients with COVID-19 at autopsy. Sections of ocular tissue from four patients were evaluated by in situ hybridization (ISH) to determine the cellular localization of SARS-CoV-2 spike gene RNA. Contralateral eyes from 21 patients were histopathologically examined. SARS-CoV-2 RNA was found in neuronal cells of the retina, ganglion cells, corneal epithelia, scleral fibroblasts, and oligodendrocytes of the optic nerve in all 21 patients. Common histopathological findings associated with infection included cytoid bodies, vascular changes, and retinal edema. Although SARS-CoV-2 infected many cell types in the eye, there was minimal to no inflammation associated with the infection.

Caption: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike RNA by in situ hybridization (ISH) in the retina. A-D: ISH for SARS-CoV-2 spike RNA (brown dots) primarily located in the outer nuclear layer of the retina (arrows, A) in case E22. Fewer positive signals are noted in the inner nuclear layer (A and B) and a retinal ganglion cell in case E23 (arrow, B). Panels A and B are with the SARS-CoV-2 spike RNA probe, and panels C and D are negative control probe for DapB. Scale bars = 20 mm. GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer (Credit: The American Journal of Pathology).

Dr Chertow comments: “In conclusion, a range of common histopathologic alterations were identified within ocular tissue, and SARS-CoV-2 RNA was localized to multiple cell types. What was surprising was the absence of inflammation, contrasting with what we have seen in other viral infections of the eye such as herpesvirus, where infection is typically associated with significant inflammation and tissue damage. The study shows important new insights into SARS-CoV-2 ocular pathogenesis. Specifically, this is the first report to definitively localize SARS-CoV-2 to the retinal inner and outer nuclear cells, retinal ganglion cells, and ocular surface by ISH, validating previous studies that have exclusively used PCR-based methods.”

This research highlights that the eye is a potential target of SARS-CoV-2 infection and supports the need to evaluate possible short- or longer-term ocular consequences of COVID-19.

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Notes for editors

The article is “Histopathology and SARS-CoV-2 Cellular Localization in Eye Tissues of COVID-19 Autopsies,” by H. Nida Sen, MD, MHSc, Kevin M. Vannella, PhD, Yujuan Wang, MD, Joon-Yong Chung, PhD, Shilpa Kodati, MD, Sabrina C. Ramelli, PhD, Jung Wha Lee, PhD, Paola Perez, PhD, Sydney R. Stein, DVM, MPH, Alison Grazioli, MD, James M. Dickey, Kris Ylaya, Manmeet Singh, PhD, Kwe Claude Yinda, PhD, Andrew Platt, MD, PhD, Marcos J. Ramos-Benitez, PhD, Christa Zerbe, MD, MS, Vincent J. Munster, PhD, Emmie de Wit, PhD, Blake M. Warner, DDS, PhD, MPH, Daniel L. Herr, MD, Joseph Rabin, MD, Kapil K. Saharia, MD, NIH COVID-19 Autopsy Consortium, David E. Kleiner, MD, PhD, Stephen M. Hewitt, MD, PhD, Chi-Chao Chan, MD, and Daniel S. Chertow, MD, MPH (https://doi.org/10.1016/j.ajpath.2023.02.016opens in new tab/window). It appears online in advance of The American Journal of Pathology, volume 193, issue 11 (November 2023), published by Elsevier.

The article is openly available at https://ajp.amjpathol.org/article/S0002-9440(23)00086-X/fulltextopens in new tab/window and is part of a special themed issue entitled Microbiome and Ocular Health: Insights and Perspectives.

The study was supported by the Intramural Research Programs of the NIH Clinical Center, National Institute of Allergy and Infectious Diseases, National Eye Institute, and National Cancer Institute.

Full text of the article is also available to credentialed journalists upon request. Contact Eileen Leahy at +1 732 238 3628 or [email protected]opens in new tab/window to request a PDF of the article. To request an interview with the authors please contact C. Yvonne Hylton, Media Lead, NIH Clinical Center, Office of Communications and Media Relations, at +1 240 731 4843 (mobile) or [email protected]opens in new tab/window.

About The American Journal of Pathology

The American Journal of Pathologyopens in new tab/window, official journal of the American Society for Investigative Pathologyopens in new tab/window, published by Elsevier, seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches. https://ajp.amjpathol.orgopens in new tab/window

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