Covid not only infects human retina, but can also replicate in it

Though SARS-CoV-2, virus causing Covid-19, majorly causes infections of the respiratory tract, it also affects other organs of the human body such as the eyes and brain.

While there is growing evidence to show that coronaviruses can enter the retina of the eye, German researchers have now shown that the virus can also replicate in human eyes.

According to the study, published in the Stem Cell Reports, SARS-CoV-2 actually infects retinal cells, especially retinal ganglion cells, but also light-sensitive cells.

Furthermore, the researchers show that coronaviruses can also replicate in these cell types. This finding is new and underlines the need to monitor retinal pathologies as a possible consequence of 'Long Covid'.

A team of researchers from the Max Planck Institute for Molecular Biomedicine and the Westfalische Wilhelms-Universitat Munster utilised organoids, an organ-like model system, of the retina from human reprogrammed stem cells to study SARS-CoV-2 infection of the retina.

The retinal organoids were incubated with SARS-CoV-2 viruses and then using quantitative PCR analysis, the researchers succeeded in detecting Covid mRNA in the organoids, indicating that cells in the organoids were indeed infected by the virus.

To measure the active virus concentrations produced by the infected organoids after different incubation times, the researchers used an assay called a "viral plaque assay". Indeed, the assay showed that new viral progeny has been formed in the retinal organoids.A

"This is the first demonstration that SARS-CoV-2 replicates in human retinal cells," said Thomas Rauen from Max Planck.

To find out which cells in the retinal organoids are affected, the researchers analysed the organoids under a fluorescence microscope. With the help of different immune markers for the different cell types of the retina and with a fluorescent antibody against the nucleoprotein (N-protein) of SARS-CoV-2, they found that mainly two cell layers - inner and outer - of the retinal organoids were infected.

The outer nuclear layer of the organoids contains the cell bodies of the photoreceptors -- the cones and rods that convert incoming light into nerve impulses.

"However, the cell type in which we most frequently detected the N-protein of Sars-CoV-2 is retinal ganglion cells," Yotam Menuchin-Lasowski from the Institute.

These cells are located in the innermost cell layer of the retina and transmit all signals from the retina to the brain via the optic nerve.

Interestingly, many of the retinal symptoms associated with Covid-19 are related to retinal ganglion cells, but these have previously been associated predominantly with secondary effects of other Covid-induced disease symptoms, such as damage to blood vessels or an increase in eye pressure.

"However, our current retina-organoid study shows that infection with SARS-CoV-2 can have direct pathological consequences for retinal ganglion cells, even though visual impairment is not common in patients with Covid-19," Rauen said.

"But our data give us reason to believe that so-called long-Covid symptoms may include degenerative retinal disease."