Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia

Abstract Background Olfactory dysfunction represents one of the most frequent symptoms of coronavirus disease 2019, affecting about 70 per cent of patients. However, the pathogenesis of the olfactory dysfunction in coronavirus disease 2019 has not yet been elucidated. Case report This report presents the radiological and histopathological findings of a patient who presented with anosmia persisting for more than three months after infection with severe acute respiratory syndrome coronavirus-2. Conclusion The biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.

Download Full-text

Severe Acute Respiratory Syndrome Coronavirus 2 Infects and Damages the Mature and Immature Olfactory Sensory Neurons of Hamsters

Clinical Infectious Diseases ◽

10.1093/cid/ciaa995 ◽

2020 ◽

Cited By ~ 11

Author(s):

Anna Jinxia Zhang ◽

Andrew Chak-Yiu Lee ◽

Hin Chu ◽

Jasper Fuk-Woo Chan ◽

Zhimeng Fan ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Olfactory Bulb ◽

Sensory Neurons ◽

Young Patients ◽

Olfactory Dysfunction ◽

Olfactory Sensory Neurons ◽

Specific Class ◽

Olfactory Neurons ◽

Viral Antigens ◽

Sustentacular Cells

Abstract Background Coronavirus disease 2019 (COVID-19) is primarily an acute respiratory tract infection. Distinctively, a substantial proportion of COVID-19 patients develop olfactory dysfunction. Especially in young patients, loss of smell can be the first or only symptom. The roles of inflammatory obstruction of the olfactory clefts, inflammatory cytokines affecting olfactory neuronal function, destruction of olfactory neurons or their supporting cells, and direct invasion of olfactory bulbs in causing olfactory dysfunction are uncertain. Methods We investigated the location for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the olfactory epithelium (OE) to the olfactory bulb in golden Syrian hamsters. Results After intranasal inoculation with SARS-CoV-2, inflammatory cell infiltration and proinflammatory cytokine/chemokine responses were detected in the nasal turbinate tissues. The responses peaked between 2 and 4 days postinfection, with the highest viral load detected at day 2 postinfection. In addition to the pseudo-columnar ciliated respiratory epithelial cells, SARS-CoV-2 viral antigens were also detected in the mature olfactory sensory neurons labeled by olfactory marker protein, in the less mature olfactory neurons labeled by neuron-specific class III β-tubulin at the more basal position, and in the sustentacular cells, resulting in apoptosis and severe destruction of the OE. During the entire course of infection, SARS-CoV-2 viral antigens were not detected in the olfactory bulb. Conclusions In addition to acute inflammation at the OE, infection of mature and immature olfactory neurons and the supporting sustentacular cells by SARS-CoV-2 may contribute to the unique olfactory dysfunction related to COVID-19, which is not reported with SARS-CoV-2.

Download Full-text

Valproic acid ameliorates olfactory dysfunction in APP/PS1 transgenic mice of Alzheimer's disease: Ameliorations from the olfactory epithelium to the olfactory bulb

Pharmacology Biochemistry and Behavior ◽

10.1016/j.pbb.2016.02.012 ◽

2016 ◽

Vol 144 ◽

pp. 53-59 ◽

Cited By ~ 8

Author(s):

Zhi-Gang Yao ◽

Hai-Yan Jing ◽

Dong-Mei Wang ◽

Bei-Bei Lv ◽

Jia-Mei Li ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Valproic Acid ◽

Olfactory Bulb ◽

Transgenic Mice ◽

Olfactory Epithelium ◽

Olfactory Dysfunction

Download Full-text

Long COVID neuropsychological deficits after severe, moderate or mild infection

10.1101/2021.02.24.21252329 ◽

2021 ◽

Author(s):

P. Voruz ◽

G. Allali ◽

L. Benzakour ◽

A. Nuber-Champier ◽

M. Thomasson ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Severe Acute Respiratory Syndrome ◽

Respiratory Symptoms ◽

Psychiatric Symptoms ◽

Olfactory Dysfunction ◽

Neuropsychological Deficits ◽

Post Discharge ◽

The Central Nervous System

ABSTRACTBackgroundThere is growing awareness that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can include long-term neuropsychological deficits, even in its mild or moderate respiratory forms.MethodsStandardized neuropsychological, psychiatric, neurological and olfactory tests were administered to 45 patients (categorized according to the severity of their respiratory symptoms during the acute phase) 236.51 ± 22.54 days post-discharge following SARS-CoV-2 infection.ResultsDeficits were found in all the domains of cognition and the prevalence of psychiatric symptoms was also high in the three groups. The severe performed more poorly on long-term episodic memory and exhibited greater anosognosia. The moderate had poorer emotion recognition, which was positively correlated with persistent olfactory dysfunction. The mild were more stressed, anxious and depressed.ConclusionThe data support the hypothesis that the virus targets the central nervous system (and notably the limbic system), and support the notion of different neuropsychological phenotypes.

Download Full-text

Region Specific Amyloid-β Accumulation in Olfactory Sensory Neurons Influences Ecto-Ventral Olfactory Dysfunction in 5xFAD Mice

10.21203/rs.3.rs-53345/v1 ◽

2020 ◽

Author(s):

Gowoon Son ◽

Seung-Jun Yoo ◽

Shinwoo Kang ◽

Ameer Rasheed ◽

Da Hae Jung ◽

...

Keyword(s):

Olfactory Bulb ◽

Sensory Neurons ◽

Olfactory Epithelium ◽

Olfactory System ◽

Amyloid Β ◽

Olfactory Dysfunction ◽

Olfactory Sensory Neurons ◽

Basal Cells ◽

Irreversible Damage ◽

5Xfad Mouse

Abstract Background: Hyposmia in Alzheimer’s disease (AD) is a typical early symptom according to numerous previous clinical studies. Although the causes of damage have been proposed in every olfactory system including olfactory epithelium, olfactory bulb and olfactory cortex, the main causes of AD- related hyposmia are largely unknown. Methods: We here focused on peripheral olfactory sensory neurons (OSNs) and delved deeper into the direct relationship between pathophysiological and behavioral results using odorants. We also histologically confirmed the pathological changes in three-month-old 5xFAD mouse models which recapitulates AD pathology. We introduced a numeric scale histologically to compare physiological phenomenon and local tissue lesions regardless of anatomical plane. Results: We observed the odorant group, which 5xFAD mouse could not detect, also neither did physiologically activate the OSNs that propagate to the ventral olfactory bulb. Interestingly, the amount of accumulated amyloid-β (Aβ) was high in the ecto-ventrally located OSNs that showed reduced responses to odorants. We also observed irreversible damage to the ecto-region of the olfactory epithelium by measuring impaired neuronal turnover ratio from the basal cells to the matured OSNs. Conclusions: Our results showed that partial and asymmetrical accumulation of Aβ coincided with physiologically and structurally damaged areas in the peripheral olfactory system, which evoked hyporeactivity to some odorants. Taken together, partial olfactory dysfunction closely-associated with peripheral OSN’s loss could be a leading cause of the AD-related hyposmia, a characteristic of early AD.

Download Full-text

Recovery of Anosmia in Hamsters Infected With SARS-CoV-2 Is Correlated With Repair of the Olfactory Epithelium

10.21203/rs.3.rs-841631/v1 ◽

2021 ◽

Author(s):

Rachel Reyna ◽

Megumi Kishimoto-Urata ◽

Shinji Urata ◽

Tomoko Makishima ◽

Slobodan Paessler ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Economic Impact ◽

Olfactory Epithelium ◽

Strong Correlation ◽

Screening Method ◽

Behavioral Test ◽

Hamster Model ◽

Effective Screening ◽

Histological Damage

Abstract Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for a pandemic affecting millions of people worldwide. Apart from the extreme global economic impact, the pandemic will likely have a lasting impact through long-term sequelae not yet fully understood. Fully understanding the mechanisms driving the various symptoms and sequelae of SARS-CoV-2 infection will allow for the eventual development of therapeutics to prevent or treat such life-altering symptoms. In this study, we developed a behavioral test of anosmia in SARS-CoV-2-infected hamsters. We find a moderately strong correlation between the level of anosmia and the score of histological damage within the olfactory epithelium. We also find a moderately strong correlation between the level of anosmia and the thickness of the olfactory epithelium, previously demonstrated to be severely damaged upon infection. Thus, this food-searching behavioral test can act as a simple and effective screening method in a hamster model for various therapeutics for SARS-CoV-2-related anosmia.

Download Full-text

Diffuse Alveolar Hemorrhage (DAH) Associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Case Report

10.21203/rs.3.rs-555436/v1 ◽

2021 ◽

Author(s):

Haytham Wali ◽

Deanne Tabb ◽

Saeed A. Baloch

Keyword(s):

Case Report ◽

Severe Acute Respiratory Syndrome ◽

Red Blood Cells ◽

Blood Cells ◽

Diffuse Alveolar Hemorrhage ◽

Alveolar Hemorrhage ◽

Rare Syndrome ◽

Novel Coronavirus

Abstract Diffuse alveolar hemorrhage (DAH) is a rare syndrome resulting from the accumulation of intra-alveolar red blood cells (RBCs) originating most often from the alveolar capillaries and, less frequently, from precapillary arterioles or postcapillary venules. The causes of DAH can be divided into infectious and noninfectious. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that has not been previously identified in humans, and it is responsible for the coronavirus disease-19 (COVID-19) infection. The long-term complications of COVID-19 are not entirely known and are still being investigated. Here, we present a case of DAH that is believed to be a consequence of COVID-19 infection.

Download Full-text

Recovery of anosmia in hamsters infected with SARS-CoV-2 is correlated with repair of the olfactory epithelium

Scientific Reports ◽

10.1038/s41598-021-04622-9 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Rachel A. Reyna ◽

Megumi Kishimoto-Urata ◽

Shinji Urata ◽

Tomoko Makishima ◽

Slobodan Paessler ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Economic Impact ◽

Olfactory Epithelium ◽

Strong Correlation ◽

Screening Method ◽

Behavioral Test ◽

Hamster Model ◽

Effective Screening ◽

Histological Damage

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for a pandemic affecting billions of people worldwide. Apart from the extreme global economic impact, the pandemic will likely have a lasting impact through long-term sequelae not yet fully understood. Fully understanding the mechanisms driving the various symptoms and sequelae of SARS-CoV-2 infection will allow for the eventual development of therapeutics to prevent or treat such life-altering symptoms. In this study, we developed a behavioral test of anosmia in SARS-CoV-2-infected hamsters. We find a moderately strong correlation between the level of anosmia and the score of histological damage within the olfactory epithelium. We also find a moderately strong correlation between the level of anosmia and the thickness of the olfactory epithelium, previously demonstrated to be severely damaged upon infection. Thus, this food-searching behavioral test can act as a simple and effective screening method in a hamster model for various therapeutics for SARS-CoV-2-related anosmia.

Download Full-text

Long COVID Neuropsychological Deficits After Severe, Moderate or Mild Infection

10.21203/rs.3.rs-383226/v1 ◽

2021 ◽

Author(s):

Philippe Voruz ◽

Gilles Allali ◽

Lamyae Benzakour ◽

Anthony Nuber-Champier ◽

Marine Thomasson ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Severe Acute Respiratory Syndrome ◽

Respiratory Symptoms ◽

Psychiatric Symptoms ◽

Olfactory Dysfunction ◽

Neuropsychological Deficits ◽

Post Discharge ◽

The Central Nervous System

Abstract Background: There is growing awareness that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can include long-term neuropsychological deficits, even in its mild or moderate respiratory forms.Methods: Standardized neuropsychological, psychiatric, neurological and olfactory tests were administered to 45 patients (categorized according to the severity of their respiratory symptoms during the acute phase) 236.51 ± 22.54 days post-discharge following SARS-CoV-2 infection. Results: Deficits were found in all the domains of cognition and the prevalence of psychiatric symptoms was also high in the three groups. The severe performed more poorly on long-term episodic memory and exhibited greater anosognosia. The moderate had poorer emotion recognition, which was positively correlated with persistent olfactory dysfunction. The mild were more stressed, anxious and depressed.Conclusion: The data support the hypothesis that the virus targets the central nervous system (and notably the limbic system), and support the notion of different neuropsychological phenotypes.

Download Full-text