It is now widely known that COVID-19 is associated with the transient or long-term loss of olfaction (the sense of smell) but the mechanisms remain obscure. An unresolved question is whether the olfactory nerve can provide SARS-CoV-2 with a route of entry to the brain. Scientists at the Max Planck Research Unit for Neurogenetics in Frankfurt in collaboration with physicians and scientists at the University Hospitals Leuven (Leuven, Belgium) and a major hospital in Bruges, Belgium, together with scientists at NanoString Technologies Inc. in Seattle, USA, report that SARS-CoV-2 does not appear to infect the sensory neurons of the olfactory epithelium in COVID-19 patients. Moreover, the team failed to find evidence for infection of olfactory bulb neurons. Instead, the sustentacular cells, also known as 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 visualizing, in distinct colors, RNA molecules that are characteristic of various cell types, in combination with classical cell staining methods using antibodies. “Our results show that SARS-CoV-2 infects sustentacular cells in the olfactory epithelium of COVID-19 patients and replicates vigorously within these cells,” says Peter Mombaerts, director of the Max Planck Research Unit for Neurogenetics.

Applying a novel approach of whole-transcriptome analysis using Digital Spatial Profiler from NanoString Technologies Inc., analysis of sections of the olfactory mucosa of a COVID-19 patient revealed that infection of sustentacular cells does not alter the expression of olfactory receptor genes in nearby olfactory sensory neurons.

Viral RNA could not be detected in olfactory bulb neurons either. Thus, the results do not support previous suggestions 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 ty transient insufficient support from sustentacular cells to olfactory sensory neurons. The virus would thus affect olfactory sensory neurons indirectly but without infecting them directly. The pathological consequences of infection of sustentacular cells could vary from patient to patient. The researchers speculate that the immune system may be unable to provide sustentacular cells with full protection from infection, due to their location at the surface of the nasal mucosa. They further speculate that some vaccinated or recovered patients may still lose their sense of smell after exposure to SARS-CoV-2.

 

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MPG

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