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Persistent and transient olfactory deficits in COVID-19 are associated to inflammation and zinc homeostasis

Lupi et al., Frontiers in Immunology, doi:10.3389/fimmu.2023.1148595
Jul 2023  
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Analysis of gene expression in the olfactory epithelium of 21 COVID-19 patients with persistent, transient, or no loss of smell. Authors find:
- Patients with persistent smell loss had higher expression of metallothionein genes involved in zinc homeostasis compared to other groups. Authors hypothesize that inflammation leads to overexpression of these genes, which sequester zinc ions and lower local zinc levels. This may impair olfactory receptor signaling and prevent recovery.
- All COVID-19 groups showed altered expression of genes related to immune/inflammatory responses compared to healthy controls, even months after diagnosis. This suggests prolonged inflammation may be a factor in persistent symptoms.
- The results suggest that zinc deficiency could contribute to loss of smell symptoms in some patients. Zinc supplementation could potentially help by restoring beneficial zinc-dependent processes.
Lupi et al., 14 Jul 2023, USA, peer-reviewed, mean age 34.0, 14 authors.
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Persistent and transient olfactory deficits in COVID-19 are associated to inflammation and zinc homeostasis
Lorenzo Lupi, Anna Bordin, Gabriele Sales, Davide Colaianni, Adriana Vitiello, Alberto Biscontin, Alberto Reale, Alfredo Garzino-Demo, Angelo Antonini, Giancarlo Ottaviano, Carla Mucignat, Cristina Parolin, Arianna Calistri, Cristiano De Pittà
Frontiers in Immunology, doi:10.3389/fimmu.2023.1148595
Introduction: The Coronavirus Disease 2019 (COVID-19) is mainly a respiratory syndrome that can affect multiple organ systems, causing a variety of symptoms. Among the most common and characteristic symptoms are deficits in smell and taste perception, which may last for weeks/months after COVID-19 diagnosis owing to mechanisms that are not fully elucidated. Methods: In order to identify the determinants of olfactory symptom persistence, we obtained olfactory mucosa (OM) from 21 subjects, grouped according to clinical criteria: i) with persistent olfactory symptoms; ii) with transient olfactory symptoms; iii) without olfactory symptoms; and iv) non-COVID-19 controls. Cells from the olfactory mucosa were harvested for transcriptome analyses. Results and discussion: RNA-Seq assays showed that gene expression levels are altered for a long time after infection. The expression profile of micro RNAs appeared significantly altered after infection, but no relationship with olfactory symptoms was found. On the other hand, patients with persistent olfactory deficits displayed increased levels of expression of genes involved in the inflammatory response and zinc homeostasis, suggesting an association with persistent or transient olfactory deficits in individuals who experienced SARS-CoV-2 infection.
Ethics statement The studies involving human participants were reviewed and approved by Ethical Committee, Azienda Ospedaliera di Padova, Padova, Italy. The patients/participants provided their written informed consent to participate in this study. Author contributions LL: investigation, methodology, data analysis and curation, validation, writing-original draft, writing-review and editing. AB: investigation, clinical data. GS: statistical analysis and curation. DC: methodology, data analysis, writing-review and editing. AV: investigation; methodology. ABi: validation, data analysis and curation. AR: investigation, methodology. AG: supervision, writing-review and editing. AA: funding acquisition, conceptualization. GO: investigation, clinical data, writing-review and editing. CM: investigation, methodology, writing-review and editing. CP: funding acquisition, conceptualization, writing-review and editing. AC: funding acquisition, conceptualization, supervision, writing-original draft, writing-review and editing. CDP: conceptualization, supervision, writing-original draft, writing-review and editing. All authors contributed to the article and approved the submitted version. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily..
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