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

Abstract

ARS-CoV-2 is an enveloped positive-sense RNA coronavirus belonging to the Coronaviridae family, and its cellular entry depends mainly on the binding of S protein 1,2 to angiotensin-converting enzyme 2, a specific cellular receptor located at the surface of the host cells. 3,4 The SARS-CoV-2 viral particles' presence in the retina of deceased patients with COVID-19 has been suggested through the real-time polymerase chain reaction (PCR) and immunological methods to detect its main proteins. The eye is affected by COVID-19 infection, 5,6 and retinal changes were attributed to secondary microvascular and immunological changes. The aim of this study was to detect the presence of presumed SARS-CoV-2 viral particles in the retina of individuals who died of COVID-19 using fluorescence microcopy of tissues immunostained for S1 and nucleocapsid proteins and transmission electron microscopy of thin sections. MethodsThis investigational study was approved by the ethical and research committee at the Federal University of São Paulo in São Paulo, Brazil, and all patients' representatives agreed to participate through written consent applied after the patient's death. They were informed of the procedure and potential benefits and risks, and no compensation was received for agreeing to participate. Detailed demographic, medical history, concomitant events, medication history, hospitalization details, 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 PARTICIPANTSThe 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 MEASURESPresence 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 dou...

Ocular and Systemic Complications of COVID-19: Impact on Patients and Healthcare

“…Histopathologic specimens from the retinas of deceased patients with COVID-19 have found presumed SARS-CoV-2 viral particles in the ganglion cell layer, inner plexiform, inner nuclear, outer plexiform, outer nuclear layer, retinal pigment epithelium, and choroid. 41 A literature review found that COVID-19 was associated with an 8.86-fold risk of retinal vascular microvasculopathy, including retinal hemorrhages, cotton wool spots, infarcts at the internal plexus, and thinner ganglion cell layer and inner nuclear layer. 42 More severe systemic disease was associated with lower vascular density on OCT angiography (OCTA).…”

Retinal Vein Occlusion Following Two Doses of mRNA-1237 (Moderna) Immunization for SARS-Cov-2: A Case Report

“…Numerous case reports and studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have revealed the retinal manifestations of the disease, which include arterial and venous thrombosis associated with macular edema (ME), haemorrhages, microvascular alterations and acute macular neuroretinopathy [ 1 – 5 ]. In addition, SARS-CoV-2 viral particles were reported to be present in human retina specimens from deceased patients infected with the disease [ 6 , 7 ]. However, it is unclear whether the reported findings are incidental, the result of systemic action of the virus or from direct retinal toxicity [ 8 ].…”

Hemi- and Central Retinal Vein Occlusion Associated with COVID-19 Infection in Young Patients without Known Risk Factors

“… 46 Furthermore, Araujo-Silva et al illustrated the findings of presumed viral particles within the retina of three deceased COVID-19 patients. 47 …”