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Disruption of nuclear architecture as a cause of COVID-19 induced anosmia.

ABSTRACT: Olfaction relies on a coordinated partnership between odorant flow and neuronal communication. Disruption in our ability to detect odors, or anosmia, has emerged as a hallmark symptom of infection with SARS-CoV-2, yet the mechanism behind this abrupt sensory deficit remains elusive. Here, using molecular evaluation of human olfactory epithelium (OE) from subjects succumbing to COVID-19 and a hamster model of SARS-CoV-2 infection, we discovered widespread downregulation of olfactory receptors (ORs) as well as key components of their signaling pathway. OR downregulation likely represents a non-cell autonomous effect, since SARS-CoV-2 detection in OSNs is extremely rare both in human and hamster OEs. A likely explanation for the reduction of OR transcription is the striking reorganization of nuclear architecture observed in the OSN lineage, which disrupts multi-chromosomal compartments regulating OR expression in humans and hamsters. Our experiments uncover a novel molecular mechanism by which a virus with a very selective tropism can elicit persistent transcriptional changes in cells that evade it, contributing to the severity of COVID-19.

SUBMITTER: Zazhytska M

PROVIDER: S-EPMC7885920 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Disruption of nuclear architecture as a cause of COVID-19 induced anosmia.

Zazhytska Marianna M Kodra Albana A Hoagland Daisy A DA Fullard John F JF Shayya Hani H Omer Arina A Firestein Stuart S Gong Qizhi Q Canoll Peter D PD Goldman James E JE Roussos Panos P tenOever Benjamin R BR Overdevest Jonathan B JB Lomvardas Stavros S

bioRxiv : the preprint server for biology 20210209

Olfaction relies on a coordinated partnership between odorant flow and neuronal communication. Disruption in our ability to detect odors, or anosmia, has emerged as a hallmark symptom of infection with SARS-CoV-2, yet the mechanism behind this abrupt sensory deficit remains elusive. Here, using molecular evaluation of human olfactory epithelium (OE) from subjects succumbing to COVID-19 and a hamster model of SARS-CoV-2 infection, we discovered widespread downregulation of olfactory receptors (OR ...[more]

PMID: 33594368

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Project description:Background: This systematic review had three aims: i) to determine the frequency of anosmia (or other smell disorders) and dysgeusia (or other taste disorders) in COVID-19 patients; ii) to determine whether anosmia or dysgeusia are independently associated with COVID-19 diagnosis; and iii) to determine whether anosmia or dysgeusia are prognostic factors for impaired outcomes among COVID-19 patients. Methods: On April 20 th, 2020, we search MEDLINE, Embase, Global Health, Scopus, Web of Science and MedXriv. We used terms related to COVID-19, smell and taste disorders. We selected case series, cross-sectional, case-control and cohort studies. We included studies with COVID-19 patients describing their symptoms; studies that compared smell and taste disorders between COVID-19 patients and otherwise healthy subjects; and studies comparing smell and taste disorders between COVID-19 severe and mild/moderate cases. Because of methodological heterogeneity and the limited number of results, a qualitative synthesis is presented. Results: From 31 reports, we selected six (n=2,757). Six studies reported the proportion of smell and taste disorders among COVID-19 patients. Two reports studied whether smell and taste disorders were independently associated with COVID-19 diagnosis. No reports studied the association with impaired outcomes among COVID-19 patients. The frequency of anosmia ranged between 22%-68%. The definition of taste disorders varied greatly, with dysgeusia present in 33% and ageusia in 20%. People who reported loss of smell and taste had six-fold higher odds of being COVID-19 positive; similarly, anosmia and ageusia were associated with 10-fold higher odds of COVID-19 diagnosis. Conclusions: The frequency of smell and taste disorders is as high as other symptoms, thus, at least anosmia for which the definition was more consistent, could be included in lists of COVID-19 symptoms. Although there is promising evidence, it is premature to conclude that smell and taste disorders are strongly associated with COVID-19 diagnosis. Registration: PROSPERO CRD42020181308.

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Disruption of nuclear architecture as a cause of COVID-19 induced anosmia.

Publications

Disruption of nuclear architecture as a cause of COVID-19 induced anosmia.

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