Presumed SARS-CoV-2 Viral Particles in the Human Retina of Patients With COVID-19 | Ophthalmology | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

Presumed SARS-CoV-2 Viral Particles in the Human Retina of Patients With COVID-19

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Is the SARS-CoV-2 virus present in the human retina?

Findings  In this case series of 3 individuals, S and N COVID-19 proteins were seen by immunofluorescence microscopy within endothelial cells close to the capillary flame and cells of the inner and the outer nuclear layers. At the perinuclear region of these cells, it was possible to observe by transmission electron microscopy double-membrane vacuoles that were consistent with the virus, presumably containing COVID-19 viral particles.

Meaning  The present observations show presumed SARS-CoV-2 viral particles may reach the various layers of the human retina and also could be associated with this infection’s ocular clinical manifestations.

Abstract

Importance  The presence of the SARS-CoV-2 virus in the retina of deceased patients with COVID-19 has been suggested through real-time reverse polymerase chain reaction and immunological methods to detect its main proteins. The eye has shown abnormalities associated with COVID-19 infection, and retinal changes were presumed to be associated with secondary microvascular and immunological changes.

Objective  To demonstrate the presence of presumed SARS-CoV-2 viral particles and its relevant proteins in the eyes of patients with COVID-19.

Design, Setting, and Participants  The retina from enucleated eyes of patients with confirmed COVID-19 infection were submitted to immunofluorescence and transmission electron microscopy processing at a hospital in São Paulo, Brazil, from June 23 to July 2, 2020. After obtaining written consent from the patients’ families, enucleation was performed in patients deceased with confirmed SARS-CoV-2 infection. All patients were in the intensive care unit, received mechanical ventilation, and had severe pulmonary involvement by COVID-19.

Main Outcomes and Measures  Presence of presumed SARS-CoV-2 viral particles by immunofluorescence and transmission electron microscopy processing.

Results  Three patients who died of COVID-19 were analyzed. Two patients were men, and 1 was a woman. The age at death ranged from 69 to 78 years. Presumed S and N COVID-19 proteins were seen by immunofluorescence microscopy within endothelial cells close to the capillary flame and cells of the inner and the outer nuclear layers. At the perinuclear region of these cells, it was possible to observe by transmission electron microscopy double-membrane vacuoles that are consistent with the virus, presumably containing COVID-19 viral particles.

Conclusions and Relevance  The present observations show presumed SARS-CoV-2 viral particles in various layers of the human retina, suggesting that they may be involved in some of the infection’s ocular clinical manifestations.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Corresponding Author: Alléxya A. A. Marcos, MD, Federal University of São Paulo-UNIFESP, R. Botucatu, 822 Vila Clementino, São Paulo, São Paulo 04023-062, Brazil (allexya.affonso@gmail.com).

Accepted for Publication: June 14, 2021.

Published Online: July 29, 2021. doi:10.1001/jamaophthalmol.2021.2795

Author Contributions: Drs Belfort and de Sousa had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Araújo-Silva, Marcos, Branco, Roque, Schor, Nascimento, de Souza, Belfort.

Acquisition, analysis, or interpretation of data: Araújo-Silva, Marcos, Marinho, Branco, Romano, Matuoka, Farah, Burnier, Moraes, Tierno, Sakamoto, de Souza, Belfort.

Drafting of the manuscript: Araújo-Silva, Marcos, Marinho, Branco, Matuoka, Sakamoto, Nascimento, Belfort.

Critical revision of the manuscript for important intellectual content: Araújo-Silva, Marcos, Branco, Roque, Romano, Farah, Burnier, Moraes, Tierno, Schor, de Souza, Belfort.

Statistical analysis: Araújo-Silva.

Obtained funding: de Souza, Belfort.

Administrative, technical, or material support: Marcos, Marinho, Branco, Matuoka, Moraes, Tierno, Sakamoto, Belfort.

Supervision: Branco, Romano, Farah, Burnier, Schor, Nascimento, de Souza, Belfort.

Conflict of Interest Disclosures: None reported.

Funding/Support: The work has received sponsorship from Conselho Nacional de Pesquisa, Instituto da Visão, and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior).

Role of the Funder/Sponsor: The work has received sponsorship from Conselho Nacional de Pesquisa, Instituto da Visão, and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for the following phases of the study: design and conduct and collection, management, analysis, and interpretation of the data.

References
1.
Ke  Z , Oton  J , Qu  K ,  et al.  Structures and distributions of SARS-CoV-2 spike proteins on intact virions.   Nature. 2020;588(7838):498-502. doi:10.1038/s41586-020-2665-2PubMedGoogle ScholarCrossref
2.
Yao  H , Song  Y , Chen  Y ,  et al.  Molecular architecture of the SARS-CoV-2 virus.   Cell. 2020;183(3):730-738.e13. doi:10.1016/j.cell.2020.09.018PubMedGoogle ScholarCrossref
3.
Walls  AC , Park  YJ , Tortorici  MA , Wall  A , McGuire  AT , Veesler  D .  Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein.   Cell. 2020;181(2):281-292.e6. doi:10.1016/j.cell.2020.02.058PubMedGoogle ScholarCrossref
4.
Zhou  P , Yang  XL , Wang  XG ,  et al.  A pneumonia outbreak associated with a new coronavirus of probable bat origin.   Nature. 2020;579(7798):270-273. doi:10.1038/s41586-020-2012-7PubMedGoogle ScholarCrossref
5.
Kaya  H , Çalışkan  A , Okul  M , Sarı  T , Akbudak  İH .  Detection of SARS-CoV-2 in the tears and conjunctival secretions of coronavirus disease 2019 patients.   J Infect Dev Ctries. 2020;14(9):977-981. doi:10.3855/jidc.13224PubMedGoogle ScholarCrossref
6.
Güemes-Villahoz  N , Burgos-Blasco  B , García-Feijoó  J ,  et al.  Conjunctivitis in COVID-19 patients: frequency and clinical presentation.   Graefes Arch Clin Exp Ophthalmol. 2020;258(11):2501-2507. doi:10.1007/s00417-020-04916-0PubMedGoogle ScholarCrossref
7.
Fiocruz. Kit molecular SARS-CoV-2 (informações e consulta de manuais). Published November 11, 2020. Accessed June 25, 2021. https://www.bio.fiocruz.br/index.php/br/produtos/reativos/testes-moleculares/novo-coronavirus-sars-cov2
8.
Caldas  LA , Carneiro  FA , Monteiro  FL ,  et al.  Intracellular host cell membrane remodelling induced by SARS-CoV-2 infection in vitro.   Biol Cell. 2021;113(6):281-293. doi:10.1111/boc.202000146PubMedGoogle ScholarCrossref
9.
Trypsteen  W , Van Cleemput  J , Snippenberg  WV , Gerlo  S , Vandekerckhove  L .  On the whereabouts of SARS-CoV-2 in the human body: a systematic review.   PLoS Pathog. 2020;16(10):e1009037. doi:10.1371/journal.ppat.1009037PubMedGoogle Scholar
10.
Casagrande  M , Fitzek  A , Püschel  K ,  et al.  Detection of SARS-CoV-2 in human retinal biopsies of deceased COVID-19 patients.   Ocul Immunol Inflamm. 2020;28(5):721-725. doi:10.1080/09273948.2020.1770301PubMedGoogle ScholarCrossref
11.
Caldas  LA , Carneiro  FA , Higa  LM ,  et al.  Ultrastructural analysis of SARS-CoV-2 interactions with the host cell via high resolution scanning electron microscopy.   Sci Rep. 2020;10(1):16099. doi:10.1038/s41598-020-73162-5PubMedGoogle ScholarCrossref
12.
Klein  S , Cortese  M , Winter  SL ,  et al.  SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography.   Nat Commun. 2020;11(1):5885. doi:10.1038/s41467-020-19619-7PubMedGoogle ScholarCrossref
13.
Snijder  EJ , Limpens  RWAL , de Wilde  AH ,  et al.  A unifying structural and functional model of the coronavirus replication organelle: tracking down RNA synthesis.   PLoS Biol. 2020;18(6):e3000715. doi:10.1371/journal.pbio.3000715PubMedGoogle Scholar
14.
Marinho  PM , Marcos  AAA , Romano  AC , Nascimento  H , Belfort  R  Jr .  Retinal findings in patients with COVID-19.   Lancet. 2020;395(10237):1610. doi:10.1016/S0140-6736(20)31014-XPubMedGoogle ScholarCrossref
15.
Schnichels  S , Rohrbach  JM , Bayyoud  T , Thaler  S , Ziemssen  F , Hurst  J .  Can SARS-CoV-2 infect the eye?: an overview of the receptor status in ocular tissue.  Article in German.  Ophthalmologe. 2020;117(7):618-621. doi:10.1007/s00347-020-01160-zPubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close