SARS-CoV-2 (CoV-2) is a pandemic coronavirus that causes the COVID-19 syndrome, which can include upper respiratory infection (URI) symptoms, severe respiratory distress, acute cardiac injury and death. Clinical reports suggest that infection with CoV-2 is associated with high rates of disturbances in smell and taste perception, including anosmia. While many viruses induce transient changes in odor perception due to inflammatory responses, in at least some cases COVID-related anosmia has been reported to occur in the absence of significant nasal inflammation or coryzal symptoms. This observation suggests that CoV-2 might directly target odor processing mechanisms, although the specific means through which CoV-2 alters odor perception remains unknown. As part of a paper we recently posted to bioRxiv, we queried both new and previously published bulk RNA-Seq and scSeq datasets from the olfactory system for expression of Ace2, Tmprss2 and other genes implicated in coronavirus entry. This analysis revealed that in mouse and human olfactory epithelium ACE2 transcripts are absent from olfactory sensory neurons but present in both sustentacular cells and horizonal basal cells. We performed a similar analysis in mouse olfactory bulb, which revealed that neurons fail to express Ace2 (either in the olfactory bulb or in the rest of the brain), but that high levels of Ace2 expression are observed in vascular pericytes. These preliminary data suggest that non- neuronal cell types are the primary target of SARS-CoV2, and represent the likely mechanism through which the virus causes anosmia. However, these preliminary data are based upon single cell sequencing, which is biased in terms of the cell types captured, under-represents gene expression, and fails to identify the distribution of Ace2 protein (which is the relevant molecule for SARS-CoV-2 entry). Here we request supplementary funding to perform in situ, immunohistochemistry and single cell sequencing experiments to comprehensively characterize the expression of Ace2 and other SARS-CoV-2 entry genes in all cell types in the olfactory system. The results of these experiments will have significant implications for our understanding of disease mechanisms, and represents a key first step towards developing strategies for addressing any long-term olfactory-related sequelae of SARS-CoV-2.
In a significant subset of patients SARS-CoV-2, the casual agent in the COVID-19 syndrome, causes anosmia, the loss of the sense of smell. Here, we propose experiments to identify cells within the olfactory system that could be infected and thereby damaged by SARS-CoV-2. This work will shed light on the mechanisms through which SARS-CoV-2 causes changes in smell perception.
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