Ocular Pathology and Occasionally Detectable Intraocular Severe Acute Respiratory Syndrome Coronavirus-2 RNA in Five Fatal Coronavirus Disease-19 Cases

Abstract

Introduction In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic broke out. The virus rapidly spread globally, resulting in a major world public-health crisis. The major disease manifestation occurs in the respiratory tract. However further studies documented other systemic involvement. This study investigate histopathologic eye changes in post-mortem material of Coronavirus Disease 2019 (COVID-19) patients. Methods Sections of formalin-fixed, paraffin-embedded eyes from 5 patients (10 eyes) who died of COVID-19 at the University Hospital in Basel were included. Gross examination and histological evaluation were performed by three independent ophthalmopathologists. Immunohistochemical staining was performed using antibodies against fibrin, cleaved caspase 3 and ACE-2. Five enucleated eyes of patients not infected with SARS-CoV-2 served as control group. All cases have been studied for presence of SARS-CoV-2 RNA by means of RT-PCR and RNA in situ hybridization. The choroidal vessels of one case were analyzed with electron microscope. Results Ophthalmopathologically, eight eyes from four patients displayed swollen endothelial cells in congested choroidal vessels. No further evidence of specific eye involvement of SARS-CoV-2 was found in any of the patients. In the eight eyes with evidence of changes due to SARS-CoV-2, immunohistochemical staining demonstrated fibrin microthrombi, apoptotic changes of endothelial and inflammatory cells. In control eyes, ACE-2 was detectable in the conjunctiva, cornea, retina and in the choroidea, and displayed significantly lower amounts of stained cells as in COVID-19 eyes. SARS-CoV-2 RNA was detectable in both bulbi of 2/5 patients, yet in situ hybridization failed to visualize viruses. Electron microscopy showed no significant results due to the artifacts. Discussion/Conclusion As already described in other organs of COVID-19 patients, the ophthalmological examination revealed-microthrombi, i.e. hypercoagulation and vasculopathy most probably due to endothelial damage. A possible viral spread to the endothelial cells via ACE-2 provides one pathophysiological explanation. The expression of ACE-2 receptors in the conjunctiva hints towards its susceptibility to infection. To what extend eyes function are disrupted by SARS-CoV-2 is subject to further studies, especially in the clinic.

Expression of the SARS-CoV-2 Receptor ACE2 in Human Retina and Diabetes—Implications for Retinopathy

“…[20][21][22] Postmortem ocular tissue studies have demonstrated evidence of intraocular SARS-CoV-2 in some cases of COVID-19. 23,24 Documented severe visual loss related to COVID-19 has been reported, including acute retinal necrosis 25 and acute viral retinitis, 26 with confirmed SARS-CoV-2 positivity on vitreous testing. Greater attention to potentially pathogenic retinal damage and infection is warranted.…”

Unilateral acute posterior multifocal placoid pigment epitheliopathy in a convalescent COVID-19 patient

“…This choroidal inflammation may be generated solely by the entry of SARS-CoV-2 via the angiotensin-converting enzyme 2 receptor (ACE) in the endothelium. The presence and abundance of this receptor has already been found higher in COVID-19 fatal cases compared to controls [17]. In these patients the accumulation of mononuclear cells and neutrophils in the lumen and intima of choriocapillaris may prove the viral trigger for white dot syndromes.…”

Retinal microvascular and perfusional disruption in paediatric COVID-19: A case-control optical coherence tomography angiography study

“…These findings were not observed in control eyes, suggesting that they were related to COVID-19. [23] SARS-CoV-2 RNA was detected in three enucleated eyes of 14 dead COVID-19 patients. [24] The findings thus far suggest ocular involvement in COVID-19 patients.…”