SARS-CoV-2 viral particles may reach the retina of COVID-19 patients

The authors investigated the presence of presumed SARS-CoV-2 viral particles in the eyes of patients who had died of COVID-19 and found evidence of the virus in multiple layers of the retina and choroid.

Study design

The authors evaluated the presence of presumed SARS-CoV-2 viral particles and relevant proteins in the eyes of patients with COVID-19 who presented to a hospital in São Paulo, Brazil, from June 23 to July 2, 2020. Enucleation was performed in deceased patients who had confirmed SARS-CoV-2 infection accompanied by severe pulmonary involvement. The authors evaluated the retina from the enucleated eyes using fluorescence microcopy of tissues immunostained for S1 and nucleocapsid proteins and transmission electron microscopy of thin sections.

Outcomes

Three patients who died of COVID-19 were analyzed. 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. Fundus examination of the first patient, a 70-year-old man with a history of hypertension, diabetes mellitus, and pulmonary emphysema, demonstrated a vitreous hemorrhage in the right eye and a normal optic disc with sharp margins in the left eye, indicating a temporal subretinal hemorrhage as well as increased vessel tortuosity. The other 2 patients had no ophthalmologic evaluations because they died shortly after admission. The macroscopic examination showed absence of inflammatory lesions or other pathologic changes in all patients.

Limitations

The authors did not examine the eyes with routine light microscopic techniques to screen for abnormalities in these tissues, such as the presence of inflammation; there was a small number of patients, and there was no proven pathogenic viral effect in the retina. However, two separate analyses confirm that SARS-CoV-2 viral particles may penetrate the retina. First, transmission electron microscopy of thin sections showed the presence of presumed virus particles with a morphology similar to that observed in cell cultures experimentally infected with the virus. Second, the characteristic S and N viral proteins were visualized using immunofluorescence microscopy. Thus, the findings are in close agreement with previous recent reports showing the presence of the S1 protein in the neurosensory retina.

Clinical significance

The eye has shown abnormalities associated with COVID-19 infection, and retinal changes were presumed to be associated with secondary microvascular and immunologic changes. However, these observations provide important evidence that SARS-CoV-2 viral particles may reach multiple layers of the human retina and choroid of patients who have died of severe COVID-19 infection. This is an important finding that suggests that SARS-CoV-2 becomes disseminated throughout the body in patients with severe infections and could be associated with the ocular clinical manifestations found in patients with COVID-19. The findings may help to elucidate the virus’ pathophysiologic mechanisms, which may direct some avenues of future research and may allow a better understanding of the sequelae of COVID-19.