Tissue-specific evidence for SARS-CoV-2 within intraocular tissues

ABSTRACT

Purpose: To systematically investigate ocular changes in autopsied eyes from fatal cases of Coronavirus disease 2019 (COVID-19) and to investigate the localization of severe acute respiratory syndrome coronavirus (SARS-CoV-2) within ocular structures. Methods: Macroscopic and microscopic histopathological evaluation was performed and the localization of SARS-CoV-2 RNA within ocular tissues investigated using an in situ hybridization (ISH) technique in 13 eyes. Contralateral eyes were freshly dissected, and droplet digital polymerase chain reaction (ddPCR) assay was performed on ocular fluids and tissues to quantify SARS-CoV-2 RNA. Results: A total of 21 fatal COVID-19 cases were included (mean age, 60.2 years [range, 27- 91 years];23.8% female). Histopathological abnormalities include vascular changes (61.9%), cytoid bodies (52.4%), and retinal edema (23.8%) with minimal inflammation (0.09%) were observed. Non-CMV viral inclusions were identified in one eye. No CMV positivity was detected. Of the 21 contralateral eyes tested by ddPCR, 14 tested positive for SARS-CoV-2. Using ddPCR and ISH, SARS-CoV-2 localization was observed in the following ocular tissues and fluid cornea (27.3%), aqueous (26.3%), lens (54.5%), vitreous (15.0%), retina (22.2%), choroid/sclera (47.4%), and optic nerve (50.0%). The choroid/sclera, optic nerve and lens were the most frequent ocular structures found to be ddPCR positive. Evidence of replication was detected in four cases. Conclusions: Our results suggest that SARS-CoV-2 localizes to intraocular tissues. However, histological changes observed are likely a secondary hemodynamic change rather than primary effect of the virus.