SARS-CoV-2 Can Infect And Replicate In Retinal Cells

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A new study by researchers from Max Planck Institute for Molecular Biomedicine has discovered that the SARS-CoV-2 coronavirus is able to infect and replicate in the photoreceptor and also retinal ganglion cells of human retinal organoids.

Past research has pointed to retinal involvement in COVID 19 disease, yet many questions remain regarding the ability of SARS-CoV-2 to infect and replicate in retinal cells and its effects on the retina.

The study findings were published on a preprint server and are currently being peer reviewed.

https://www.biorxiv.org/content/10.1101/2021.10.09.463766v1

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that is responsible for millions of fatalities. While mild-to-severe respiratory symptoms are most commonly associated with the disease (Huang et al., 2020), neurological (Asadi-Pooya and Simani, 2020; Mao et al., 2020) and ocular (Wu et al., 2020) symptoms have also been described in patients.

Growing evidence suggests retinal involvement in some cases of COVID-19.

Different reports identified SARS-CoV-2 RNA in retinal and optic nerve biopsies taken from deceased COVID- 19 patients (Casagrande et al., 2020; Casagrande et al., 2021), while different retinal anomalies were also identified in patients (Burgos-Blasco et al., 2020; Conrady et al., 2021; Marinho et al., 2020; Pereira et al., 2020; Rodriguez-Rodriguez et al., 2021; Virgo and Mohamed, 2020). Yet, retinal involvement in COVID-19 remains a controversial topic, as other studies were not able to detect retinal pathologies in patients (Pirraglia et al., 2020).

Furthermore, one study reported failure to isolate virus from SARS-CoV-2 RNA–positive retinal biopsies and an inability to detect any SARS-CoV-2 spike protein from those biopsies by immunohistochemical analysis, leading investigators to suggest that SARS-CoV-2 can infect but not actively replicate in retinal cells (Casagrande et al., 2021).

It also remains unclear which retinal structures are infected by SARS-CoV-2 and whether the retinal anomalies reported are due to retinal infection or systemic organ dysfunction (Casagrande et al., 2020; de Figueiredo et al., 2020).

Organoids are three-dimensional, tissue cultures that resemble specific organs in their morphology, cell-type composition, or function. Different research groups have used organoids generated from human stem cells to study the infection of SARS-CoV-2 in the context of different organs (Lamers et al., 2020; Monteil et al., 2020; Pellegrini et al., 2020; Ramani et al., 2020; Zhang et al., 2020).

Such studies have demonstrated that SARS-CoV-2 can infect neurons and neural progenitors (Ramani et al., 2020; Zhang et al., 2020). Retinal organoids are among the most physiologically accurate neural organoid models, as they contain all the major retinal cell types, follow a developmental trajectory similar to that of the human retina in vivo, and are correctly organized in a typical layered structure (Achberger et al., 2019; Nakano et al., 2012; Zhong et al., 2014).

Here we use retinal organoids to show that SARS-CoV-2 can infect retinal cells, mainly retinal ganglion cells (RGCs) but also photoreceptors, as well as replicate in them.

Moreover, retinal SARS-CoV-2 infection induces the expression of several inflammatory genes and is reduced by treatment of the organoids with an anti-ACE-2 antibody.

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