Olfactory dysfunction in COVID-19: new insights into the underlying mechanisms

Butowt, Rafał; Bilińska, Katarzyna; Bartheld, Christopher S. von

doi:10.1016/j.tins.2022.11.003

Cited by 51 publications

(65 citation statements)

References 118 publications

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“…Two main reasons have been proposed to explain this phenomenon, and they are not mutually exclusive. The mutations in the spike protein make the omicron variant more hydrophobic [101] which may reduce the solubility of the virus in the mucus, diminishing its ability to reach the olfactory epithelium [2,102]. Second, due to reduced furin cleavage, the omicron variant prefers an endosomal route via cathepsin for entering host cells rather than a surface membrane fusion via the protease TMPRSS2 [103].…”

Section: Discussionmentioning

confidence: 99%

“…Sustentacular cells and Bowman gland cells are the cells in the olfactory epithelium which most abundantly express not only ACE2, but also TMPRSS2 [104,105] and for this reason these support cells were the prime target of previous SARS-CoV-2 variants for host cell entry via the route using cell surface membrane fusion enabled by TMPRSS2 [106]. Since the support cells – similar to many other host cells – have evolved more potent defense mechanisms for the endosomal route of infection [102,107], for example, the antiviral IFITM2 gene is the most highly upregulated gene in support cells at 3 days after infection [108], this may lead to a lower efficiency in omicron infection of the support cells of the olfactory epithelium, and therefore reduced olfactory dysfunction [102,109].…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the sustentacular support cell in the olfactory epithelium appears to play a major role. This helps to direct focus on this cell type and its key roles in the processing of odorants and fundamental workings of the sense of smell [102]. A better understanding of the molecular mechanisms of loss of smell in COVID may inform about new therapies to help with persistent loss of smell, beyond the current olfactory training that is not effective for more than half of cases [133].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Prevalence of Olfactory Dysfunction with the Omicron Variant of SARS-CoV-2: A Systematic Review and Meta-analysis

Bartheld

Wang

2022

Preprint

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The omicron variant is thought to cause less olfactory dysfunction than previous variants of SARS-CoV-2, but the reported prevalence differs greatly between populations and studies. Our systematic review and meta-analysis provide information about regional differences in prevalence as well as an estimate of the global prevalence of olfactory dysfunction based on 41 studies reporting on nearly 600,000 patients infected with the omicron variant. Our estimate of the omicron-induced prevalence of olfactory dysfunction in populations of European ancestry is 11.6%, while it is significantly lower in all other populations, at 2.9-5.4%. When ethnic differences and population sizes are taken into account, the global prevalence of omicron-induced hyposmia in adults is estimated at 5.2%. Omicron's effect on olfaction is 3-4fold lower than that of the alpha or delta variant, according to previous meta-analyses and our analysis of studies that directly compared prevalence of olfactory dysfunction between omicron and previous variants. The profile of prevalence differences between ethnicities mirrors the results of a recent genome-wide association study that implicated a gene locus encoding an odorant-metabolizing enzyme, UDP glycosyltransferase, to be linked to the extent of COVID-related loss of smell. Our analysis is consistent with the hypothesis that this enzyme contributes to the observed population differences.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prevalence of Olfactory Dysfunction with the Omicron Variant of SARS-CoV-2: A Systematic Review and Meta-analysis

Bartheld

Wang

2022

Preprint

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“…The clinical presentation is highly diverse, involving several organs and systems. Smell and taste disorders were particularly frequent since the initial phase of the COVID-19 pandemic (19, 20), with quantitative (hypo-, hyper-, anosmia or ageusia) or qualitative (dys-, phantosmia or phantageusia) alterations. Persistent olfactory disorders have been notified from 10% to more than 50% according to SARS-CoV-2 variants (18, 19), and can be recovered in a few months.…”

Section: Introductionmentioning

confidence: 99%

“…Smell and taste disorders were particularly frequent since the initial phase of the COVID-19 pandemic (19, 20), with quantitative (hypo-, hyper-, anosmia or ageusia) or qualitative (dys-, phantosmia or phantageusia) alterations. Persistent olfactory disorders have been notified from 10% to more than 50% according to SARS-CoV-2 variants (18, 19), and can be recovered in a few months. Nevertheless, recent data described less than 40% people with a complete recovery after 2 years, and 7.5% displaying no improvement (21).…”

Section: Introductionmentioning

confidence: 99%

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

Denis¹,

Garnier²,

Cheutin³

et al. 2023

Preprint

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Current approved COVID-19 vaccines, notably mRNA and adenoviral vectored technologies, still fail to fully protect against infection and transmission of various SARS-CoV-2 variants. The mucosal immunity at the upper respiratory tract represents the first line of defense against respiratory viruses such as SARS-CoV-2 and is thus critical to develop vaccine blocking human-to-human transmission. We measured systemic and mucosal Immunoglobulin A (IgA) response in serum and saliva from 133 healthcare workers from Percy teaching military hospital following a mild infection (SARS-CoV-2 Wuhan strain, n=58) or not infected (n=75), and after SARS-CoV-2 vaccination (Vaxzevria/Astrazeneca and/or Comirnaty/Pfizer). While serum anti-SARS-CoV-2 Spike IgA response lasted up to 16 months post-infection, IgA response in saliva had mostly fallen to baseline level at 6 months post-infection. Vaccination could reactivate the mucosal response generated by prior infection, but failed to induce a significant mucosal IgA response by itself. As breakthrough infections have been correlated with IgA levels, other vaccine platforms inducing a better mucosal immunity are needed to control COVID-19 infection in the future. Early post-COVID-19 serum anti-Spike-NTD IgA titer correlated with seroneutralization titers. Interestingly, its saliva counterpart positively correlated with persistent smell and taste disorders more than one year after mild COVID-19, and could potentially be used as an early prognosis biomarker.

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Pro‐inflammatory markers associated with COVID‐19‐related persistent olfactory dysfunction

Jang,

Pak,

Strom

et al. 2023

Int Forum Allergy Rhinol

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IntroductionWhile localized inflammation has been implicated in the pathophysiology of acute coronavirus disease of 2019 (COVID‐19) olfactory dysfunction (OD), persistent COVID‐19 OD remains poorly understood with limited therapeutics. Our prospective study evaluated olfactory cleft (OC) biomarkers as predictors of persistent OD in mucus sampling.MethodsCOVID‐19 subjects with persistent OD >3 months confirmed by psychophysical olfaction tests were compared to COVID‐19 subjects with no OD and those with no prior infection. OC mucus samples were evaluated for 13 anti‐viral and inflammatory biomarkers. Cohorts were compared using analysis of variance (ANOVA) and Mann–Whitney tests with multi‐comparison adjustment. Viral RNA was assessed through RT‐PCR using the COVID‐19 N2 primer.ResultsThirty‐five samples were collected (20 COVID persistent OD, 8 COVID no OD, and 7 non‐COVID no OD). Significant differences in IFN‐λ1 (p = 0.007) and IFN‐γ (p = 0.006) expression in OC mucus were found across all three groups, with the highest cytokine concentrations corresponding to COVID OD. IFN‐α2 levels were elevated in COVID OD versus no OD (p = 0.026). Mean IFN‐γ levels were the highest in COVID OD, but there were higher levels found in COVID no OD compared to non‐COVID no OD (p = 0.008). No difference was seen in IL6. No N2 gene expression was detected in all cohorts.ConclusionIFN pathway cytokines were found elevated in the olfactory microenvironment of COVID‐19 persistent OD compared to those with no OD and no prior history of COVID‐19 infection.

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Olfactory dysfunction in COVID-19: new insights into the underlying mechanisms

Cited by 51 publications

References 118 publications

Prevalence of Olfactory Dysfunction with the Omicron Variant of SARS-CoV-2: A Systematic Review and Meta-analysis

Prevalence of Olfactory Dysfunction with the Omicron Variant of SARS-CoV-2: A Systematic Review and Meta-analysis

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

Pro‐inflammatory markers associated with COVID‐19‐related persistent olfactory dysfunction

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