Histopathology and SARS-CoV-2 Cellular Localization in Eye Tissues of COVID-19 Autopsies

NIH COVID-19 Autopsy Consortium

doi:10.1016/j.ajpath.2023.02.016

Histopathology and SARS-CoV-2 Cellular Localization in Eye Tissues of COVID-19 Autopsies

NIH COVID-19 Autopsy Consortium

Surgery, Trauma and Critical Care Division

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Ophthalmic manifestations and tissue tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in association with coronavirus disease 2019 (COVID-19), but the pathology and cellular localization of SARS-CoV-2 are not well characterized. The objective of this study was to evaluate macroscopic and microscopic changes and investigate cellular localization of SARS-CoV-2 across ocular tissues at autopsy. Ocular tissues were obtained from 25 patients with COVID-19 at autopsy. SARS-CoV-2 nucleocapsid gene RNA was previously quantified by droplet digital PCR from one eye. Herein, contralateral eyes from 21 patients were fixed in formalin and subject to histopathologic examination. Sections of the droplet digital PCR–positive eyes from four other patients were evaluated by in situ hybridization to determine the cellular localization of SARS-CoV-2 spike gene RNA. Histopathologic abnormalities, including cytoid bodies, vascular changes, and retinal edema, with minimal or no inflammation in ocular tissues were observed in all 21 cases evaluated. In situ hybridization localized SARS-CoV-2 RNA to neuronal cells of the retinal inner and outer layers, ganglion cells, corneal epithelia, scleral fibroblasts, and oligodendrocytes of the optic nerve. In conclusion, a range of common histopathologic alterations were identified within ocular tissue, and SARS-CoV-2 RNA was localized to multiple cell types. Further studies will be required to determine whether the alterations observed were caused by SARS-CoV-2 infection, the host immune response, and/or preexisting comorbidities.

Original language	English (US)
Pages (from-to)	1809-1816
Number of pages	8
Journal	American Journal of Pathology
Volume	193
Issue number	11
DOIs	https://doi.org/10.1016/j.ajpath.2023.02.016
State	Published - Nov 2023

Funding

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 . This research was in part made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation , Genentech , the American Association for Dental Research , and the Colgate-Palmolive Company .

ASJC Scopus subject areas

Pathology and Forensic Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ajpath.2023.02.016

Cite this

@article{2885a25e8bac4944af19a4268e4ba35c,

title = "Histopathology and SARS-CoV-2 Cellular Localization in Eye Tissues of COVID-19 Autopsies",

abstract = "Ophthalmic manifestations and tissue tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in association with coronavirus disease 2019 (COVID-19), but the pathology and cellular localization of SARS-CoV-2 are not well characterized. The objective of this study was to evaluate macroscopic and microscopic changes and investigate cellular localization of SARS-CoV-2 across ocular tissues at autopsy. Ocular tissues were obtained from 25 patients with COVID-19 at autopsy. SARS-CoV-2 nucleocapsid gene RNA was previously quantified by droplet digital PCR from one eye. Herein, contralateral eyes from 21 patients were fixed in formalin and subject to histopathologic examination. Sections of the droplet digital PCR–positive eyes from four other patients were evaluated by in situ hybridization to determine the cellular localization of SARS-CoV-2 spike gene RNA. Histopathologic abnormalities, including cytoid bodies, vascular changes, and retinal edema, with minimal or no inflammation in ocular tissues were observed in all 21 cases evaluated. In situ hybridization localized SARS-CoV-2 RNA to neuronal cells of the retinal inner and outer layers, ganglion cells, corneal epithelia, scleral fibroblasts, and oligodendrocytes of the optic nerve. In conclusion, a range of common histopathologic alterations were identified within ocular tissue, and SARS-CoV-2 RNA was localized to multiple cell types. Further studies will be required to determine whether the alterations observed were caused by SARS-CoV-2 infection, the host immune response, and/or preexisting comorbidities.",

author = "{NIH COVID-19 Autopsy Consortium} and Sen, {H. Nida} and Vannella, {Kevin M.} and Yujuan Wang and Chung, {Joon Yong} and Shilpa Kodati and Ramelli, {Sabrina C.} and Lee, {Jung Wha} and Paola Perez and Stein, {Sydney R.} and Alison Grazioli and Dickey, {James M.} and Kris Ylaya and Manmeet Singh and Yinda, {Kwe Claude} and Andrew Platt and Ramos-Benitez, {Marcos J.} and Christa Zerbe and Munster, {Vincent J.} and {de Wit}, Emmie and Warner, {Blake M.} and Herr, {Daniel L.} and Joseph Rabin and Saharia, {Kapil K.} and Platt, {Andrew P.} and Curran, {Shelly J.} and Babyak, {Ashley L.} and Valencia, {Luis Perez} and Richert, {Mary E.} and Chertow, {Daniel S.} and Kleiner, {David E.} and Hewitt, {Stephen M.} and Young, {Willie J.} and Young, {Sarah P.} and Billel Gasmi and {De Melo}, {Michelly Sampaio} and Sabina Desar and Saber Tadros and Nadia Nasir and Xueting Jin and Sharika Rajan and Esra Dikoglu and Neval Ozkaya and Stefania Pittaluga and Grace Smith and Emanuel, {Elizabeth R.} and Brian Kelsall and Olivera, {Justin A.} and Megan Blawas and Nicole Hays and Herrold, {Joseph A.}",

note = "Publisher Copyright: {\textcopyright} 2023 American Society for Investigative Pathology",

year = "2023",

month = nov,

doi = "10.1016/j.ajpath.2023.02.016",

language = "English (US)",

volume = "193",

pages = "1809--1816",

journal = "American Journal of Pathology",

issn = "0002-9440",

publisher = "Elsevier Inc.",

number = "11",

}

TY - JOUR

T1 - Histopathology and SARS-CoV-2 Cellular Localization in Eye Tissues of COVID-19 Autopsies

AU - NIH COVID-19 Autopsy Consortium

AU - Sen, H. Nida

AU - Vannella, Kevin M.

AU - Wang, Yujuan

AU - Chung, Joon Yong

AU - Kodati, Shilpa

AU - Ramelli, Sabrina C.

AU - Lee, Jung Wha

AU - Perez, Paola

AU - Stein, Sydney R.

AU - Grazioli, Alison

AU - Dickey, James M.

AU - Ylaya, Kris

AU - Singh, Manmeet

AU - Yinda, Kwe Claude

AU - Platt, Andrew

AU - Ramos-Benitez, Marcos J.

AU - Zerbe, Christa

AU - Munster, Vincent J.

AU - de Wit, Emmie

AU - Warner, Blake M.

AU - Herr, Daniel L.

AU - Rabin, Joseph

AU - Saharia, Kapil K.

AU - Platt, Andrew P.

AU - Curran, Shelly J.

AU - Babyak, Ashley L.

AU - Valencia, Luis Perez

AU - Richert, Mary E.

AU - Chertow, Daniel S.

AU - Kleiner, David E.

AU - Hewitt, Stephen M.

AU - Young, Willie J.

AU - Young, Sarah P.

AU - Gasmi, Billel

AU - De Melo, Michelly Sampaio

AU - Desar, Sabina

AU - Tadros, Saber

AU - Nasir, Nadia

AU - Jin, Xueting

AU - Rajan, Sharika

AU - Dikoglu, Esra

AU - Ozkaya, Neval

AU - Pittaluga, Stefania

AU - Smith, Grace

AU - Emanuel, Elizabeth R.

AU - Kelsall, Brian

AU - Olivera, Justin A.

AU - Blawas, Megan

AU - Hays, Nicole

AU - Herrold, Joseph A.

PY - 2023/11

Y1 - 2023/11

N2 - Ophthalmic manifestations and tissue tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in association with coronavirus disease 2019 (COVID-19), but the pathology and cellular localization of SARS-CoV-2 are not well characterized. The objective of this study was to evaluate macroscopic and microscopic changes and investigate cellular localization of SARS-CoV-2 across ocular tissues at autopsy. Ocular tissues were obtained from 25 patients with COVID-19 at autopsy. SARS-CoV-2 nucleocapsid gene RNA was previously quantified by droplet digital PCR from one eye. Herein, contralateral eyes from 21 patients were fixed in formalin and subject to histopathologic examination. Sections of the droplet digital PCR–positive eyes from four other patients were evaluated by in situ hybridization to determine the cellular localization of SARS-CoV-2 spike gene RNA. Histopathologic abnormalities, including cytoid bodies, vascular changes, and retinal edema, with minimal or no inflammation in ocular tissues were observed in all 21 cases evaluated. In situ hybridization localized SARS-CoV-2 RNA to neuronal cells of the retinal inner and outer layers, ganglion cells, corneal epithelia, scleral fibroblasts, and oligodendrocytes of the optic nerve. In conclusion, a range of common histopathologic alterations were identified within ocular tissue, and SARS-CoV-2 RNA was localized to multiple cell types. Further studies will be required to determine whether the alterations observed were caused by SARS-CoV-2 infection, the host immune response, and/or preexisting comorbidities.

AB - Ophthalmic manifestations and tissue tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in association with coronavirus disease 2019 (COVID-19), but the pathology and cellular localization of SARS-CoV-2 are not well characterized. The objective of this study was to evaluate macroscopic and microscopic changes and investigate cellular localization of SARS-CoV-2 across ocular tissues at autopsy. Ocular tissues were obtained from 25 patients with COVID-19 at autopsy. SARS-CoV-2 nucleocapsid gene RNA was previously quantified by droplet digital PCR from one eye. Herein, contralateral eyes from 21 patients were fixed in formalin and subject to histopathologic examination. Sections of the droplet digital PCR–positive eyes from four other patients were evaluated by in situ hybridization to determine the cellular localization of SARS-CoV-2 spike gene RNA. Histopathologic abnormalities, including cytoid bodies, vascular changes, and retinal edema, with minimal or no inflammation in ocular tissues were observed in all 21 cases evaluated. In situ hybridization localized SARS-CoV-2 RNA to neuronal cells of the retinal inner and outer layers, ganglion cells, corneal epithelia, scleral fibroblasts, and oligodendrocytes of the optic nerve. In conclusion, a range of common histopathologic alterations were identified within ocular tissue, and SARS-CoV-2 RNA was localized to multiple cell types. Further studies will be required to determine whether the alterations observed were caused by SARS-CoV-2 infection, the host immune response, and/or preexisting comorbidities.

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UR - http://www.scopus.com/inward/citedby.url?scp=85153927038&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2023.02.016

DO - 10.1016/j.ajpath.2023.02.016

M3 - Article

C2 - 36963628

AN - SCOPUS:85153927038

SN - 0002-9440

VL - 193

SP - 1809

EP - 1816

JO - American Journal of Pathology

JF - American Journal of Pathology

IS - 11

ER -

Histopathology and SARS-CoV-2 Cellular Localization in Eye Tissues of COVID-19 Autopsies

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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