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Steffen E. Künzel, Thore Bürgel, Sandrine Künzel, Joel Howard, Alexandre Dubrac; Low vulnerability of the human retina to SARS-CoV-2 infection - potential role of the choroidal vasculature. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1158.
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Ocular manifestations have been described in COVID-19 patients, but it is unknown whether SARS-CoV-2 – the causal agent in COVID-19 – can directly infect posterior ocular tissues. Here, we investigate SARS-CoV-2 host factor gene expression levels and their distribution across retinal and choroidal cell types. The overall aim is to identify particularly vulnerable cell-types to elucidate a potential pathomechanism for observed retinal lesions in COVID-19 patients.
Datasets from human retina and choroid were retrieved from published datasets. We reprocessed the data from raw quantification matrix following standard Seurat (v.3.1) clustering procedure. To take advantage of the improved Seurat pre-processing and normalization workflow, we used the SCTransform function, thereby we “corrected” log-normalized expression values across datasets. To reannotate the cells, multiple clusterings of different resolutions were generated among which the one best matching published clustering was picked and manual annotation was undertaken using marker genes.
Key genes for SARS-CoV-2 host cell entry are significantly lower expressed in human retinal cell-types compared to choroid. In detail, we observe no expression of ACE2 or TMPRSS2 in the retina, but a scarce co-expression in vessel associated cell-types of the choroid. No differences could be detected between fovea and periphery for both tissues.
Key conclusion:The human retina is not vulnerable for a direct SARS-CoV-2 infection. Thus, retinal lesions as described in a recent Lancet publication by Marinho et al. are most likely due to a secondary damage (Marinho et al., 2020). However, SARS-CoV-2 entry genes are expressed in vessel-associated cell-types of the choroid. Thus, as described in other organs, the virus might infect the vasculature in terms of an infectious endothelitis, and could subsequently lead to vascular occlusions. Further studies are needed to elucidate whether vascular occlusions of the posterior eye segment correlate with life-threatening cardiovascular complications in COVID-19 patients. Thus, the posterior eye segment might qualify as an in vivo biomarker of systemic vascular disease in COVID-19 patients and imaging techniques of the posterior eye segment could be helpful for manage treatment of COVID-19 patients.
This is a 2021 ARVO Annual Meeting abstract.
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