Neurological

SARS-CoV-2 infects sustentacular cells in the olfactory epithelium of COVID-19 patients

It is now well known that COVID-19 has been linked to temporary or long-term loss of the sense of smell (smell), but the mechanisms behind it remain unclear. An unanswered question is whether the SARS-CoV-2 olfactory nerve can provide an access route to the brain. Scientists from the Max Planck Research Center for Neurogenetics in Frankfurt in collaboration with doctors and scientists from the University Hospital Leuven (Leuven, Belgium) and a large hospital in Bruges, Belgium, together with scientists from NanoString Technologies Inc. in Seattle, USA, report that SARS -CoV-2 does not appear to infect sensory neurons of the olfactory epithelium in COVID-19 patients. In addition, the team failed to find evidence of olfactory bulb neuron infection. Instead, the sustentacular cells, also called supporting cells, are the main target cell type for the virus in the olfactory epithelium. Since SARS-CoV2 spares olfactory sensory neurons and olfactory bulb neurons, it does not appear to be a neurotropic virus.

The scientists were able to assign the infected cells to specific cell types by simultaneously making RNA molecules that are characteristic for different cell types visible in different colors in combination with classic cell staining methods with antibodies. “Our results show that SARS-CoV-2 infects the sustentacular” Cells in the olfactory epithelium of COVID-19 patients and multiply in these cells, ”says Peter Mombaerts, Director of the Max Planck Research Center for Neurogenetics.

Using a novel approach to total transcriptome analysis with NanoString Technologies Inc.’s Digital Spatial Profiler, analyzing sections of the olfactory mucosa of a COVID-19 patient revealed an infection of sustentacular Cells did not alter the expression of olfactory receptor genes in nearby olfactory sensory neurons.

No viral RNA could be detected in olfactory bulb neurons either. Thus, the results do not support previous assumptions that SARS-CoV-2 can infect nerve cells in humans. In other words, SARS-CoV-2 does not appear to be a neurotropic virus. The multidisciplinary team postulates that transient olfactory dysfunction in COVID-19 is triggered by transient inadequate support from sustentacular cells to olfactory sensory neurons. The virus would thus indirectly affect olfactory sensory neurons, but without infecting them directly. The pathological consequences of an infection of sustentacle cells can vary from patient to patient. The researchers speculate that because of their location on the surface of the nasal mucosa, the immune system may not be able to fully protect sustentacular cells from infection. They further speculate that some vaccinated or recovered patients might lose their sense of smell after exposure to SARS-CoV-2.

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