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

doi:10.3389/fimmu.2023.1148595

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

Front Immunol. 2023 Jul 14:14:1148595. doi: 10.3389/fimmu.2023.1148595. eCollection 2023.

Authors

Lorenzo Lupi^{1

2}, Anna Bordin³, Gabriele Sales¹, Davide Colaianni¹, Adriana Vitiello², Alberto Biscontin¹, Alberto Reale², Alfredo Garzino-Demo^{2

4}, Angelo Antonini^{5

6}, Giancarlo Ottaviano³, Carla Mucignat², Cristina Parolin², Arianna Calistri², Cristiano De Pittà¹

Affiliations

¹ Department of Biology, University of Padova, Padova, Italy.
² Department of Molecular Medicine, University of Padova, Padova, Italy.
³ Department of Neurosciences, Otolaryngology Section, University of Padova, Padova, Italy.
⁴ Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, Maryland, United States.
⁵ Parkinson and Movement Disorders Unit, Department of Neurosciences, University of Padova, Padova, Italy.
⁶ Department of Neurosciences, University of Padova, Padova, Italy.

Abstract

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.

Keywords: RNA-seq; SARS-CoV-2; inflammation; metallothionein; miRNA; olfactory symptoms; zinc homeostasis.

MeSH terms

Adult
Aged
COVID-19* / complications
COVID-19* / immunology
Female
Gene Expression Profiling
Homeostasis*
Humans
Inflammation*
Male
Middle Aged
Olfaction Disorders* / etiology
Olfaction Disorders* / virology
Olfactory Mucosa* / metabolism
Olfactory Mucosa* / virology
SARS-CoV-2* / physiology
Smell
Transcriptome
Zinc* / metabolism

Substances

Zinc

Grants and funding

This work has been supported by Grant COVID-CNS (to AA) of Cassa di Risparmio di Padova e Rovigo (CARIPARO); Grant DOR from the University of Padova (CM), PARO_FINA20_01 (to CP), PRIN 2020LW7XWH (to AG) and the Promega Corporation 2019 Real-Time PCR Grant program (to ABi).