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. 2022 Sep-Oct;88(5):794-802.
doi: 10.1016/j.bjorl.2021.04.001. Epub 2021 Apr 25.

Pathophysiological relationship between COVID-19 and olfactory dysfunction: A systematic review

Mateus Henrique de Las Casas Lima  1 , Ana Luiza Brusiquesi Cavalcante  2 , Sydney Correia Leão  2
Affiliations

Pathophysiological relationship between COVID-19 and olfactory dysfunction: A systematic review

Mateus Henrique de Las Casas Lima et al. Braz J Otorhinolaryngol. 2022 Sep-Oct.

Abstract

Introduction: SARS-CoV-2 is the pathogen of COVID-19. The virus is composed of the spike, membrane and envelope. On physiological smell, odoriferous substances bind to proteins secreted by sustentacular cells in order to be processed by olfactory receptor neurons. Olfactory disorder is one of the main manifestations of COVID-19, however, research is still required to clarify the mechanism involved in SARS-CoV-2 induced anosmia.

Objective: This article aims to analyze current scientific evidence intended to elucidate the pathophysiological relationship between COVID-19 and the cause of olfactory disorders.

Methods: Pubmed, Embase, Scopus and ScienceDirect were used to compose this article. The research was conducted on November 24th, 2020. Original articles with experimental studies in human, animal and in vitro, short communications, viewpoint, published in the English language and between 2019 and 2020 were included, all related to the pathophysiological relationship between olfactory disorders and COVID-19 infection.

Results: Both human cell receptors ACE2 and TMPRSS2 are essential for the SARS-CoV-2 entrance. These receptors are mostly present in the olfactory epithelium cells, therefore, the main hypothesis is that anosmia is caused due to damage to non-neuronal cells which, thereafter, affects the normal olfactory metabolism. Furthermore, magnetic resonance imaging studies exhibit a relationship between a reduction on the neuronal epithelium and the olfactory bulb atrophy. Damage to non-neuronal cells explains the average recovery lasting a few weeks. This injury can be exacerbated by an aggressive immune response, which leads to damage to neuronal cells and stem cells inducing a persistent anosmia. Conductive anosmia is not sufficient to explain most cases of COVID-19 induced anosmia.

Conclusion: Olfactory disorders such as anosmia and hyposmia can be caused by COVID-19, the main mechanism is associated with olfactory epithelium damage, targeting predominantly non-neuronal cells. However, neuronal cells can also be affected, worsening the condition of olfactory loss.

Keywords: Anosmia; COVID-19; Olfaction disorders; SARS-CoV-2; Smell.

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Figures

Figure 1
Figure 1
Flowchart according to PRISMA protocol.
Figure 2
Figure 2
Mechanism of virus entry into the target cell using the ACE2 receptor aided by TMPRSS2 protease.
Figure 3
Figure 3
A, Basal stem cells; B, Sustentacular cells; C, Bowman cell; D, Olfactory receptor neurons; E, Olfactory bulb; F, Mucus. (1) Intact olfactory epithelium; (2) Arrival and invasion of SARS-CoV-2; (3) Damage to sustentacular cells, loss of cilia from olfactory receptor neurons and interruption of mucus production; (4) Regeneration of the olfactory epithelium.
See this image and copyright information in PMC

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