Oral SARS-CoV-2 Inoculation Causes Nasal Viral Infection Leading to Olfactory Bulb Infection: An Experimental Study

Ueha, Rumi; Ito, Toshihiro; Furukawa, Ryutaro; Kitabatake, Masahiro; Ouji-Sageshima, Noriko; Ueha, Satoshi; Koyama, Misaki; Uranaka, Tsukasa; Kondo, Kenji; Yamasoba, Tatsuya

doi:10.3389/fcimb.2022.924725

Cited by 12 publications

(17 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the impact of SARS-CoV-2 on each ORN lineage cell has not been sufficiently verified. We previously reported that all ORN lineage cells are impaired by SARS-CoV-2 (19), and in this study, we verified related longitudinal effects for the first time to our knowledge.…”

Section: Discussionsupporting

confidence: 85%

“…SARS-CoV-2 infected animal models were prepared following previously reported methods (19, 24). In short, the SARS-CoV-2 strain (JPN/TY/WK-521, provided by the National Institute of Infectious Diseases, Japan) was used.…”

Section: Methodsmentioning

confidence: 99%

“…The hamsters were anesthetized with an intraperitoneal injection of pentobarbital (10 mg/mL, 0.8 mL/hamster) before virus inoculation. To the SARS-CoV-2 transoral infection group, 50 μL of virus solution diluted with saline (including 1.0×10 3 pfu of SARS-CoV-2) was administered orally as previously reported (19, 24). To the control group, 50 μL of saline was administered.…”

Section: Methodsmentioning

confidence: 99%

“…We validated SARS-CoV-2 viral RNA in the lungs to confirm the SARS-CoV-2 infection status of each hamster. Total RNA was isolated from the lung using NucleoSpin ® RNA (Macherey-Nagel, Düren, Germany), and then converted to cDNA using a High-Capacity cDNA Reverse Transcription Kit (Thermo Fisher Scientific, Waltham, MA, USA), according to the previous protocol (19, 24) and the manufacturer’s instructions. RT-qPCR analysis was performed using a StepOnePlus Real-Time PCR System (Thermo Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

“…The OE is composed of supporting cells (sustentacular cells), basal progenitor cells, immature olfactory receptor cells (ORNs), and mature ORNs (18). Basal cells and supporting cells are particularly susceptible to damage by SARS-CoV-2 infection, and the entire OE may be denuded depending on the site (10, 14, 15, 19). This OE impairment improves over time, and the OE is nearly normalized within approximately 1 month after SARS-CoV-2 infection, although the regenerative kinetics may differ according to the nose area, such as the nasal septum and lateral nasal turbinate (14).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Delayed SARS-CoV-2 Spread and Olfactory Cell Lineage Impairment in Close-Contact Infection Syrian Hamster Models

Ueha

Ito

Ueha

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Objectives: Close contact with patients with COVID-19 is speculated to be the most common cause of viral transmission, but the pathogenesis of COVID-19 by close contact remains to be elucidated. In addition, despite olfactory impairment being a unique complication of COVID-19, the impact of SARS-CoV-2 on the olfactory cell lineage has not been fully validated. This study aimed to elucidate close-contact viral transmission to the nose and lungs and to investigate the temporal damage in the olfactory receptor neuron (ORN) lineage caused by SARS-CoV-2. Methods: Syrian hamsters were orally administered SARS-CoV-2 as direct-infection models. On day 7 after inoculation, infected and uninfected hamsters were housed in the same cage for 30 minutes. These uninfected hamsters were subsequently assigned to a close-contact group. First, viral presence in the nose and lungs was verified in the infection and close-contact groups at several time points. Next, the impacts on the olfactory epithelium, including olfactory progenitors, immature ORNs, and mature ORNs, were examined histologically. Then, the viral transmission status and chronological changes in tissue damage were compared between the direct-infection and close-contact groups. Results: In the close-contact group, viral presence could not be detected in both the nose and lungs on day 3, and the virus was identified in both tissues on day 7. In the direct-infection group, the viral load was highest in the nose and lungs on day 3, decreased on day 7, and was no longer detectable on day 14. Histologically, in the direct-infection group, mature ORNs were most depleted on day 3 (p < 0.001) and showed a recovery trend on day 14, with similar trends for olfactory progenitors and immature ORNs. In the close-contact group, there was no obvious tissue damage on day 3, but on day 7, the number of all ORN lineage cells significantly decreased (p < 0.001). Conclusion: SARS-CoV-2 was transmitted even after brief contact and subsequent olfactory epithelium and lung damage occurred more than 3 days after the trigger of infection. The present study also indicated that SARS-CoV-2 damages all ORN lineage cells, but this damage can begin to recover approximately 14 days post infection.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Delayed SARS-CoV-2 Spread and Olfactory Cell Lineage Impairment in Close-Contact Infection Syrian Hamster Models

Ueha

Ito

Ueha

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Neutrophils play a major role in the destruction of the olfactory epithelium during SARS-CoV-2 infection in hamsters

Bourgon

Albin

Ando-Grard

et al. 2022

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

The loss of smell (anosmia) related to SARS-CoV-2 infection is one of the most common symptoms of COVID-19. Olfaction starts in the olfactory epithelium mainly composed of olfactory sensory neurons surrounded by supporting cells called sustentacular cells. It is now clear that the loss of smell is related to the massive infection by SARS-CoV-2 of the sustentacular cells in the olfactory epithelium leading to its desquamation. However, the molecular mechanism behind the destabilization of the olfactory epithelium is less clear. Using golden Syrian hamsters infected with an early circulating SARS-CoV-2 strain harboring the D614G mutation in the spike protein; we show here that rather than being related to a first wave of apoptosis as proposed in previous studies, the innate immune cells play a major role in the destruction of the olfactory epithelium. We observed that while apoptosis remains at a low level in the damaged area of the infected epithelium, the latter is invaded by Iba1 + cells, neutrophils and macrophages. By depleting the neutrophil population or blocking the activity of neutrophil elastase-like proteinases, we could reduce the damage induced by the SARS-CoV-2 infection. Surprisingly, the impairment of neutrophil activity led to a decrease in SARS-CoV-2 infection levels in the olfactory epithelium. Our results indicate a counterproductive role of neutrophils leading to the release of infected cells in the lumen of the nasal cavity and thereby enhanced spreading of the virus in the early phase of the SARS-CoV-2 infection. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-022-04643-1.

show abstract

Insight into the mechanisms of olfactory dysfunction by COVID-19

Koyama¹,

Mori²,

Ueha³

2023

Auris Nasus Larynx

View full text Add to dashboard Cite

Oral SARS-CoV-2 Inoculation Causes Nasal Viral Infection Leading to Olfactory Bulb Infection: An Experimental Study

Cited by 12 publications

References 52 publications

Delayed SARS-CoV-2 Spread and Olfactory Cell Lineage Impairment in Close-Contact Infection Syrian Hamster Models

Delayed SARS-CoV-2 Spread and Olfactory Cell Lineage Impairment in Close-Contact Infection Syrian Hamster Models

Neutrophils play a major role in the destruction of the olfactory epithelium during SARS-CoV-2 infection in hamsters

Insight into the mechanisms of olfactory dysfunction by COVID-19

Contact Info

Product

Resources

About