Autoimmunity, COVID-19 Omicron Variant, and Olfactory Dysfunction: A Literature Review

Abstract

Smelling is a critical sense utilized daily. Consequently, smelling impairment or anosmia may lead to a reduction in life quality. Systemic diseases and particular autoimmune conditions can impair olfactory function; among others are Systemic Lupus Erythematosus, Sjögren Syndrome, and Rheumatoid Arthritis. Interactions between the olfactory process and the immune systems cause this phenomenon. Alongside autoimmune conditions, in the recent COVID-19 pandemic, anosmia was also described as a prevalent infection symptom. Nevertheless, the occurrence of anosmia is significantly less common in Omicron-infected patients. Several theories have been proposed to explain this phenomenon. One possibility is that the Omicron variant preferentially enters host cells via endocytosis, rather than plasma cell membrane fusion. This endosomal pathway is less dependent on the activation of Transmembrane serine protease 2 (TMPRSS2), expressed at the olfactory epithelium. As a result, the Omicron variant may have reduced efficiency in penetrating the olfactory epithelium, leading to a lower prevalence of anosmia. Furthermore, olfactory changes are known to be associated with inflammatory conditions. The Omicron variant elicits a less robust autoimmune and inflammatory response, believed to reduce the probability of anosmia. This review elaborates on the commonalities and differences in autoimmune and COVID-19 omicron-associated anosmia.

NETosis and SARS-COV-2 Infection-Related Autoimmunity: A Narrative Review

“…In viral infections, the virus may enter the CNS through the olfactory bulb, causing acute inflammation and demyelination of the nervous system. These olfactory changes may also have an autoimmune basis in SARS-CoV-2 infection (10). Collectively, these findings underscore that NETosis and hyperinflammation are central to the pathogenesis of severe COVID-19, highlighting the need to evaluate NETosis activity in patients and determine if it influences the clinical progression of the disease.…”

A Comprehensive Review of COVID-19-Related Olfactory Deficiency: Unraveling Associations with Neurocognitive Disorders and Magnetic Resonance Imaging Findings

“…The loss of support cells and stem cells leads to thinning and lack of repair of the OE, resulting in the loss of olfactory dendrites, which likely explains prolonged OD [22,32]. Inflammation Furthermore, persistent inflammation after invasion, resulting from the production of proinflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and CXC chemokine ligand 10 (CXCL10), appears to contribute to the development of post-COVID-19 OD, as it can directly damage the OE or interfere with cell signaling processes [13,33].…”

“…The inability or impairment of the olfactory process can lead to a markedly reduced quality of life. The lack of pleasure in eating and drinking can lead to alterations in eating and social behaviors [13].…”