The COVID-19 pandemic revealed that there is a loss of smell in many patients, including in infected but otherwise asymptomatic individuals. The underlying mechanisms for the olfactory symptoms are unclear. Using a mouse model, we determined whether cells in the olfactory epithelium express the obligatory receptors for entry of the SARS-CoV-2 virus by using RNAseq, RT-PCR, in situ hybridization, Western blot, and immunocytochemistry. We show that the cell surface protein ACE2 and the protease TMPRSS2 are expressed in sustentacular cells of the olfactory epithelium but not, or much less, in most olfactory receptor neurons. These data suggest that sustentacular cells are involved in SARS-CoV-2 virus entry and impairment of the sense of smell in COVID-19 patients. We also show that expression of the entry proteins increases in animals of old age. This may explain, if true also in humans, why individuals of older age are more susceptible to the SARS-CoV-2 infection.
The novel SARS-CoV-2 virus has very high infectivity, which allows it to spread rapidly around the world. Attempts at slowing the pandemic at this stage depend on the number and quality of diagnostic tests performed. We propose that the olfactory epithelium from the nasal cavity may be a more appropriate tissue for detection of SARS-CoV-2 virus at the earliest stages, prior to onset of symptoms or even in asymptomatic people, as compared to commonly used sputum or nasopharyngeal swabs. Here we emphasize that the nasal cavity olfactory epithelium is the likely site of enhanced binding of SARS-CoV-2. Multiple non-neuronal cell types present in the olfactory epithelium express two host receptors, ACE2 and TMPRSS2 proteases, that facilitate SARS-CoV-2 binding, replication, and accumulation. This may be the underlying mechanism for the recently reported cases of smell dysfunction in patients with COVID-19. Moreover, the possibility of subsequent brain infection should be considered which begins in olfactory neurons. In addition, we discuss the possibility that olfactory receptor neurons may initiate rapid immune responses at early stages of the disease. We emphasize the need to undertake research focused on additional aspects of SARS-CoV-2 actions in the nervous system, especially in the olfactory pathway.
It has become clear since the pandemic
broke out that SARS-CoV-2
virus causes reduction of smell and taste in a significant fraction
of COVID-19 patients. The olfactory dysfunction often occurs early
in the course of the disease, and sometimes it is the only symptom
in otherwise asymptomatic carriers. The cellular mechanisms for these
specific olfactory disturbances in COVID-19 are now beginning to be
elucidated. Several very recent papers contributed to explaining the
key cellular steps occurring in the olfactory epithelium leading to
anosmia/hyposmia (collectively known as dysosmia) initiated by SARS-CoV-2
infection. In this Viewpoint, we discuss current progress in research
on olfactory dysfunction in COVID-19 and we also propose an updated
model of the SARS-CoV-2-induced dysosmia. The emerging central role
of sustentacular cells and inflammatory processes in the olfactory
epithelium are particularly considered. The proposed model of anosmia
in COVID-19 does not answer unequivocally whether the new coronavirus
exploits the olfactory route to rapidly or slowly reach the brain
in COVID-19 patients. To answer this question, new systematic studies
using an infectious virus and appropriate animal models are needed.
After
several months of rapid pandemic expansion, it is now apparent
that the SARS-CoV-2 coronavirus interferes with smell and taste sensation
in a substantial proportion of COVID-19 patients. Recent epidemiological
data documented intriguing differences in prevalence of chemosensory
dysfunctions between different world regions. Viral genetic factors
as well as host genetic factors appear to be relevant; however, it
is not yet known which mutations or polymorphisms actually contribute
to such phenotypic differences between populations. Here, we discuss
recent genetic and epidemiological data on the D614G spike protein
variant and assess whether current evidence is consistent with the
notion that this single nucleotide polymorphism augments chemosensory
impairments in COVID-19 patients. We hypothesize that this spike variant
is an important viral genetic factor that facilitates infection of
chemosensory epithelia, possibly acting together with yet to be identified
host factors, and thereby increases smell and taste impairment. We
suggest that the prevalence of chemosensory deficits may reflect the
pandemic potential for transmissibility and spread which differs between
populations.
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