Histopathological assessments reveal retinal vascular changes, inflammation and gliosis in patients with lethal COVID-19

Abstract

Importance: We are in the midst of the human coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), which is of historic proportions, the likes of which we have not seen in 102 years. Despite being primarily a respiratory virus, COVID-19 can also present with non-respiratory signs, including ocular symptoms as conjunctival hyperemia, chemosis, epiphora, increased secretions, ocular pain, photophobia and dry eye. The virus has also been detected within the anterior chamber and in the ocular fluids suggesting that ocular tissue maybe affected due to Sars-CoV-2 infection. Objective: To assess for histopathological changes within the retina and the choroid and determine the long-term sequelae of the viral infection. Design, Setting, and Participants: 12 donor eyes from COVID-19 positive individuals and similar age matched donor eyes from patients with negative test for SARS-CoV-2 were assessed. Eyes were fixed in 4% paraformaldehyde and 0.5% glutaraldehyde in PBS within 6 hours postmortem. Main Outcomes and Measures: Globes were evaluated with macroscopic, SLO and OCT imaging. Macula and peripheral regions were processed for epon-embedding and immunocytochemistry with markers for SARS-CoV-2 infection, gliosis, inflammation and vasculature. Results: Fundus analysis shows hemorrhagic spots and increased vitreous debris in several of the COVID-19 eyes compared to the control. OCT based measurements indicated an increased trend in retinal thickness in the COVID-19 eyes, however the difference was not statistically significant. Histology of the retina showed presence of hemorrhages and central cystoid degeneration in several of the donors. Whole mount analysis of the retina labeled with markers showed changes in retinal microvasculature, increased inflammation, and gliosis in the COVID-19 eyes compared to the controls. The choroidal vasculature displayed localized changes in density and signs of increased inflammation in the COVID-19 samples. Conclusions and Relevance: In situ analysis of the retinal tissue suggested that there are severe subclinical abnormalities that could be detected in the COVID-19 eyes. This study provides a rationale for evaluating the ocular physiology of patients that have recovered from COVID-19 infections to further understand the long-term effects caused by this virus.