Researchers, including Matthew Grubb and Marcela Lipovsek from the CDN, have just shared a preprint of their manuscript on bioRxiv, detailing how the expression pattern of the SARS-CoV2 receptor, ACE2, is suggestive of the mechanisms of COVID-19-associated olfactory dysfunction.
Data emerging from the ongoing coronavirus pandemic indicates that a proportion of COVID-19 patients experience symptoms of olfactory dysfunction such as anosmia (the total or partial loss of the sense of smell) alongside the typical respiratory difficulties and fever. How and why this might happen is addressed for the first time by Brann, Tsukahara, Weinreb et al.
The paper analyses mRNA expression to see which cells in the (healthy) olfactory system are capable of producing the particular molecules that SARS-CoV2 uses to infect cells. The authors analysed both published and new bulk and single cell RNA-Seq datasets to see which cell types in the olfactory epithelium and olfactory bulb express genes encoding cell entry molecules that mediate infection by SARS-CoV2, the virus that causes COVID-19. RNA-Seq generates data on all of the genes that are expressed by particular cells which has the advantage of allowing data previously collected for other purposes to be re-analysed. Brann et al. found that two specific genes, ACE2 and TMPRSS2, were expressed in samples from whole olfactory mucosa in species including mouse and human. However, neither olfactory sensory neurons nor olfactory bulb neurons express either of these genes. Instead they are expressed in support cells, stem cells, and perivascular cells.
Their findings suggest that primary infection with SARS-CoV2 leading to a loss of a sense of smell is most likely to be through non-neuronal cell types, rather than neurons in the nose or in the brain. The authors suggest three putative (but not mutually exclusive) mechanisms by which such non-neuronal infection might produce olfactory dysfunction: an inflammatory response altering sensory and bulb neuronal function; damage to these neurons’ support cells; and support cell damage causing architectural damage to the olfactory system.
Definitive identification of the mechanisms underlying olfactory dysfunction associated with COVID-19 will require further research and data-gathering. Indeed, the natural history of COVID-19 is only just beginning to be defined.
This work therefore identifies the cells in the olfactory system that express molecules known to be involved in SARS-CoV2 infection and provides valuable insight which further studies can build upon.