Post-COVID-19 persistent olfactory, gustatory, and trigeminal chemosensory disorders: Definitions, mechanisms, and potential treatments

Abstract

The nose and the oral cavities are the main sites for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into the body. Smell and taste deficits are the most common acute viral manifestations. Persistent smell disorders are the most common and bothersome complications after SARS-CoV-2 infection, lasting for months to years. The mechanisms and treatment of persistent post-coronavirus disease 2019 (COVID-19) smell and taste disorders are still challenges. Information sources for the review are PubMed, Centers for Disease Control and Prevention, Ovid Medline, Embase, Scopus, Web of Science, International Prospective Register of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, Elton Bryson Stephens Company, Cochrane Effective Practice and Organization of Care, Cooperation in Science and Technology, International Clinical Trials Registry Platform, World Health Organization, Randomized Controlled Trial Number Registry, and MediFind. This review summarizes the up-to-date information about the prevalence, patterns at onset, and prognoses of post-COVID-19 smell and taste disorders, evidence for the neurotropism of SARS-CoV-2 and the overlap between SARS-CoV-1, Middle East respiratory syndrome coronavirus, and SARS-CoV-2 in structure, molecular biology, mode of replication, and host pathogenicity, the suggested cellular and molecular mechanisms for these post-COVID19 chemosensory disorders, and the applied pharmacotherapies and interventions as trials to treat these disorders, and the recommendations for future research to improve understanding of predictors and mechanisms of these disorders. These are crucial for hopeful proper treatment strategies.

Keywords: COVID-19; SARS-CoV-2; Coronaviruses; Olfactory and gustatory chemosensory disorders; Anosmia; Ageusia; Parosmia; Neuronal degeneration; Neurogenesis

Core Tip: Smell loss is the most frequent acute manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Persistent smell disorders (deficits and distortions) are the most frequent viral complications. Taste and flavor disorders are also complications of SARS-CoV-2 infection but at lower frequencies compared to smell disorders. It has been found that SARS-CoV-2 has a 4 times more affinity to infect the olfactory epithelium compared to other human coronaviruses. The mechanisms of these disorders have been explored mainly based on animal models of anosmia due to SARS-CoV-2 infection. It has been suggested that the post-coronavirus disease 2019 transient smell loss might be due to viral infection to the olfactory non-neuronal epithelial cells (particularly the susentacular cells) which are important for the health of olfactory sensory neurons (OSNs). These cells rapidly regenerate after injury, within 1-3 wk, and restore smell function. Persistent smell disorders have been suggested to be due to injury of OSNs, disorganization of the olfactory epithelium, altered expression of olfactory receptors, and impaired olfactory neurogenesis. These cells require ≥ 3 mo to regenerate and restore function depending on the severity and type of injury. Taste disorders have been suggested to be due to viral infection of taste buds, disruption of the activity of the salivary glands, inflammation of the gustatory epithelium, and injury to the taste sensory cells. Treatment of these disorders is a medical challenge, and none of the available pharmacotherapies or interventions which are used to treat similar disorders due to other causes, showed curative effect.