Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
1.
Viruses ; 13(11)2021 11 09.
Article in English | MEDLINE | ID: covidwho-1512699

ABSTRACT

The global pandemic of coronavirus disease (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to an international thrust to study pathogenesis and evaluate interventions. Experimental infection of hamsters and the resulting respiratory disease is one of the preferred animal models since clinical signs of disease and virus shedding are similar to more severe cases of human COVID-19. The main route of challenge has been direct inoculation of the virus via the intranasal route. To resemble the natural infection, we designed a bespoke natural transmission cage system to assess whether recipient animals housed in physically separate adjacent cages could become infected from a challenged donor animal in a central cage, with equal airflow across the two side cages. To optimise viral shedding in the donor animals, a low and moderate challenge dose were compared after direct intranasal challenge, but similar viral shedding responses were observed and no discernible difference in kinetics. The results from our natural transmission set-up demonstrate that most recipient hamsters are infected within the system developed, with variation in the kinetics and levels of disease between individual animals. Common clinical outputs used for the assessment in directly-challenged hamsters, such as weight loss, are less obvious in hamsters who become infected from naturally acquiring the infection. The results demonstrate the utility of a natural transmission model for further work on assessing the differences between virus strains and evaluating interventions using a challenge system which more closely resembles human infection.


Subject(s)
COVID-19/transmission , Disease Models, Animal , Mesocricetus , SARS-CoV-2/physiology , Animals , COVID-19/pathology , COVID-19/virology , Cricetinae , Female , Lung/pathology , Male , Nasal Cavity/pathology , Viral Load , Virus Shedding
2.
Viruses ; 13(8)2021 08 20.
Article in English | MEDLINE | ID: covidwho-1367922

ABSTRACT

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019, suffer from respiratory and non-respiratory symptoms. Among these symptoms, the loss of smell has attracted considerable attention. The objectives of this study were to determine which cells are infected, what happens in the olfactory system after viral infection, and how these pathologic changes contribute to olfactory loss. For this purpose, Syrian golden hamsters were used. First, we verified the olfactory structures in the nasal cavity of Syrian golden hamsters, namely the main olfactory epithelium, the vomeronasal organ, and their cellular components. Second, we found angiotensin-converting enzyme 2 expression, a receptor protein of SARS-CoV-2, in both structures and infections of supporting, microvillar, and solitary chemosensory cells. Third, we observed pathological changes in the infected epithelium, including reduced thickness of the mucus layer, detached epithelia, indistinct layers of epithelia, infiltration of inflammatory cells, and apoptotic cells in the overall layers. We concluded that a structurally and functionally altered microenvironment influences olfactory function. We observed the regeneration of the damaged epithelium, and found multilayers of basal cells, indicating that they were activated and proliferating to reconstitute the injured epithelium.


Subject(s)
COVID-19/virology , Chemoreceptor Cells/virology , Olfactory Mucosa/virology , SARS-CoV-2 , Vomeronasal Organ/virology , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/pathology , Chemoreceptor Cells/pathology , Male , Mesocricetus , Nasal Cavity/pathology , Nasal Cavity/virology , Olfactory Mucosa/metabolism , Olfactory Mucosa/pathology , Olfactory Receptor Neurons/metabolism , Olfactory Receptor Neurons/pathology , Olfactory Receptor Neurons/virology , Receptors, Coronavirus/metabolism , Regeneration , SARS-CoV-2/isolation & purification , Vomeronasal Organ/metabolism , Vomeronasal Organ/pathology
3.
BMJ Case Rep ; 13(9)2020 Sep 14.
Article in English | MEDLINE | ID: covidwho-1186232

ABSTRACT

Nasal granuloma gravidarum usually presents as a small vascular lesion on the septum or turbinates during pregnancy. We present a case of a giant nasal granuloma gravidarum and its management.


Subject(s)
Granuloma/surgery , Nasal Cavity/abnormalities , Adult , Female , Granuloma/pathology , Humans , Nasal Cavity/pathology , Nasal Cavity/physiopathology , Pregnancy
5.
Neurology ; 95(23): e3145-e3152, 2020 12 08.
Article in English | MEDLINE | ID: covidwho-966472

ABSTRACT

OBJECTIVE: To assess the physiopathology of olfactory function loss (OFL) in patients with coronavirus disease 2019 (COVID-19), we evaluated the olfactory clefts (OC) on MRI during the early stage of the disease and 1 month later. METHODS: This was a prospective, monocentric, case-controlled study. Twenty severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-infected patients with OFL were included and compared to 20 age-matched healthy controls. All infected patients underwent olfactory function assessment and 3T MRI, performed both at the early stage of the disease and at the 1-month follow-up. RESULTS: At the early stage, SARS-CoV2-infected patients had a mean olfactory score of 2.8 ± 2.7 (range 0-8), and MRI displayed a complete obstruction of the OC in 19 of 20 patients. Controls had normal olfactory scores and no obstruction of the OC on MRI. At the 1 month follow-up, the olfactory score had improved to 8.3 ± 1.9 (range 4-10) in patients, and only 7 of 20 patients still had an obstruction of the OC. There was a correlation between olfactory score and obstruction of the OC (p = 0.004). CONCLUSION: OFL in SARS-CoV2-infected patients is associated with a reversible obstruction of the OC.


Subject(s)
Anosmia/diagnosis , Anosmia/etiology , COVID-19/complications , Edema/pathology , Nasal Cavity/pathology , Nasal Obstruction/pathology , Adult , Anosmia/pathology , Anosmia/physiopathology , COVID-19/diagnostic imaging , COVID-19/pathology , COVID-19/physiopathology , Case-Control Studies , Edema/diagnostic imaging , Edema/etiology , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nasal Cavity/diagnostic imaging , Nasal Obstruction/diagnostic imaging , Nasal Obstruction/etiology , Young Adult
6.
EBioMedicine ; 63: 103153, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-956065

ABSTRACT

BACKGROUND: The novel human coronavirus SARS-CoV-2 is a major ongoing global threat with huge economic burden. Like all respiratory viruses, SARS-CoV-2 initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission. METHODS: SARS-CoV-2 Victoria/01/2020 was passaged in Vero/hSLAM cells and virus titre determined by plaque assay. Challenge virus was delivered by intranasal instillation to female ferrets at 5.0 × 106 pfu/ml. Treatment groups received intranasal INNA-051, developed by Ena Respiratory. SARS-CoV-2 RNA was detected using the 2019-nCoV CDC RUO Kit and QuantStudio™ 7 Flex Real-Time PCR System. Histopathological analysis was performed using cut tissues stained with haematoxylin and eosin (H&E). FINDINGS: We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. After 5 days post-exposure to SARS-CoV-2, INNA-051 significantly reduced virus in throat swabs (p=<0.0001) by up to a 24 fold (96% reduction) and in nasal wash (p=0.0107) up to a 15 fold (93% reduction) in comparison to untreated animals. INTERPRETATION: The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT, to reduce SARS-CoV-2 transmission and provide protection against COVID-19. FUNDING: This work was funded by Ena Respiratory, Melbourne, Australia.


Subject(s)
Lipopeptides/administration & dosage , Respiratory System/virology , SARS-CoV-2/pathogenicity , Toll-Like Receptor 2/agonists , Toll-Like Receptor 6/agonists , Virus Shedding , Administration, Intranasal , Animals , COVID-19/drug therapy , COVID-19/pathology , Disease Models, Animal , Female , Ferrets , Immunity, Innate , Lipopeptides/chemistry , Lipopeptides/pharmacology , Nasal Cavity/pathology , Nasal Cavity/virology , Pharynx/pathology , Pharynx/virology , RNA, Viral/metabolism , Real-Time Polymerase Chain Reaction , Respiratory System/pathology , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Viral Load/drug effects
7.
Otolaryngol Head Neck Surg ; 164(6): 1337-1344, 2021 06.
Article in English | MEDLINE | ID: covidwho-852952

ABSTRACT

OBJECTIVE: This study aimed to investigate the differences in olfactory cleft (OC) morphology in coronavirus disease 2019 (COVID-19) anosmia compared to control subjects and postviral anosmia related to infection other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). STUDY DESIGN: Prospective. SETTING: This study comprises 91 cases, including 24 cases with anosmia due to SARS-CoV-2, 38 patients with olfactory dysfunction (OD) due to viral infection other than SARS-CoV-2, and a control group of 29 normosmic cases. METHODS: All cases had paranasal sinus computed tomography (CT), and cases with OD had magnetic resonance imaging (MRI) dedicated to the olfactory nerve. The OC width and volumes were measured on CT, and T2-weighted signal intensity (SI), olfactory bulb volumes, and olfactory sulcus depths were assessed on MRI. RESULTS: This study showed 3 major findings: the right and left OC widths were significantly wider in anosmic patients due to SARS-CoV-2 (group 1) or OD due to non-SARS-CoV-2 viral infection (group 2) when compared to healthy controls. OC volumes were significantly higher in group 1 or 2 than in healthy controls, and T2 SI of OC area was higher in groups 1 and 2 than in healthy controls. There was no significant difference in olfactory bulb volumes and olfactory sulcus depths on MRI among groups 1 and 2. CONCLUSION: In this study, patients with COVID-19 anosmia had higher OC widths and volumes compared to control subjects. In addition, there was higher T2 SI of the olfactory bulb in COVID-19 anosmia compared to control subjects, suggesting underlying inflammatory changes. There was a significant negative correlation between these morphological findings and threshold discrimination identification scores. LEVEL OF EVIDENCE: Level 4.


Subject(s)
Anosmia/pathology , Anosmia/virology , COVID-19/complications , Nasal Cavity/pathology , Olfactory Bulb/pathology , Adult , Anosmia/diagnostic imaging , COVID-19/diagnostic imaging , COVID-19/pathology , Case-Control Studies , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nasal Cavity/diagnostic imaging , Olfactory Bulb/diagnostic imaging , Olfactory Mucosa/diagnostic imaging , Olfactory Mucosa/pathology , Organ Size , Prospective Studies , Tomography, X-Ray Computed
SELECTION OF CITATIONS
SEARCH DETAIL