Anosmia in COVID-19: A Bumpy Road to Establishing a Cellular Mechanism

Abstract

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.

Keywords: ACE2; Anosmia; Brain infection; COVID-19; Hyposmia; Olfactory epithelium; SARS-CoV-2.

Figure 1

Model for SARS-CoV-2-induced anosmia/hyposmia in COVID-19 based on results obtained from patients and from animal models. Sustentacular cells (SUSs) express ACE2 and are infected first. Impairment of SUS negatively affects olfactory receptor neurons (ORNs), leading to the inhibition of odor perception cascade (double lines). Simultaneously, rapid immune response is induced in a subset of ORNs and in microvillar cells (MVCs). This leads to activation of lymphocytes and macrophages and their infiltration into the OE as well as secretion of proinflammatory cytokines. It is not currently known whether SARS-CoV-2 passes to ORNs as these neurons do not express ACE2 (question mark). The possibility of infection of progenitor cells requires examination, since these cells express ACE2 and are in close contact with SUS cells (question mark). Stem cell infection may potentially explain why a small fraction of COVID-19 patients experience long-term dysosmia.