Absent Blood Oxygen Level–Dependent Functional Magnetic Resonance Imaging Activation of the Orbitofrontal Cortex in a Patient With Persistent Cacosmia and Cacogeusia After COVID-19 Infection

Ismail, Ismail Ibrahim; Gad, Khaled

doi:10.1001/jamaneurol.2021.0009

Cited by 29 publications

(41 citation statements)

References 5 publications

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“… 44 Additionally, immune-mediated olfactory neuropathy and encephalitic damage to the olfactory system accord with residual olfactory dysfunction with or without perceptual distortions (eg, parosmias and phantosmias). 65 However, these assertions could change as further post-mortem studies are completed and additional histopathological and ultrastructural data, and robust quantitative olfactometric examinations, are published. 95 Future efforts involving structural and functional MRI of the olfactory system in people with anosmia, done during the acute phase of SARS-CoV-2 infection, would help to close this knowledge gap.…”

Section: Discussionmentioning

confidence: 99%

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Post-viral effects of COVID-19 in the olfactory system and their implications

Xydakis

Albers

Holbrook

et al. 2021

The Lancet Neurology

144

153

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Background The mechanisms by which any upper respiratory virus, including SARS-CoV-2, impairs chemosensory function are not known. COVID-19 is frequently associated with olfactory dysfunction after viral infection, which provides a research opportunity to evaluate the natural course of this neurological finding. Clinical trials and prospective and histological studies of new-onset post-viral olfactory dysfunction have been limited by small sample sizes and a paucity of advanced neuroimaging data and neuropathological samples. Although data from neuropathological specimens are now available, neuroimaging of the olfactory system during the acute phase of infection is still rare due to infection control concerns and critical illness and represents a substantial gap in knowledge. Recent developments The active replication of SARS-CoV-2 within the brain parenchyma (ie, in neurons and glia) has not been proven. Nevertheless, post-viral olfactory dysfunction can be viewed as a focal neurological deficit in patients with COVID-19. Evidence is also sparse for a direct causal relation between SARS-CoV-2 infection and abnormal brain findings at autopsy, and for trans-synaptic spread of the virus from the olfactory epithelium to the olfactory bulb. Taken together, clinical, radiological, histological, ultrastructural, and molecular data implicate inflammation, with or without infection, in either the olfactory epithelium, the olfactory bulb, or both. This inflammation leads to persistent olfactory deficits in a subset of people who have recovered from COVID-19. Neuroimaging has revealed localised inflammation in intracranial olfactory structures. To date, histopathological, ultrastructural, and molecular evidence does not suggest that SARS-CoV-2 is an obligate neuropathogen. Where next? The prevalence of CNS and olfactory bulb pathosis in patients with COVID-19 is not known. We postulate that, in people who have recovered from COVID-19, a chronic, recrudescent, or permanent olfactory deficit could be prognostic for an increased likelihood of neurological sequelae or neurodegenerative disorders in the long term. An inflammatory stimulus from the nasal olfactory epithelium to the olfactory bulbs and connected brain regions might accelerate pathological processes and symptomatic progression of neurodegenerative disease. Persistent olfactory impairment with or without perceptual distortions (ie, parosmias or phantosmias) after SARS-CoV-2 infection could, therefore, serve as a marker to identify people with an increased long-term risk of neurological disease.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, in patients with COVID-19, normal structural radiographic morphology does not rule out aberrant functional neuronal electrical activity within the olfactory pathways, as evidenced by abnormal findings on functional MRI and PET-CT scans. 64 , 65 …”

Section: Evidence From Neuroimagingmentioning

confidence: 99%

Post-viral effects of COVID-19 in the olfactory system and their implications

Xydakis

Albers

Holbrook

et al. 2021

The Lancet Neurology

144

153

View full text Add to dashboard Cite

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“…TRCs within taste buds contain interferon receptors, and a systemic response to virus should eliminate the virus while simultaneously leading to taste changes. 28 While we did not investigate it directly it is possible that there could be indirect effects on the neuronal 30 or blood supply to the taste buds as is noted by the detection of ACE2 in the proximity of the taste buds. We further propose that deficient stem cell turnover will result in TRCs not being effectively replaced and that this explains why some people have slow recovery of their complete taste repertoire.…”

Section: Discussionmentioning

confidence: 99%

Human Type II Taste Cells Express Angiotensin-Converting Enzyme 2 and Are Infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Doyle

Appleton

Liu

et al. 2021

The American Journal of Pathology

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Chemosensory changes are well-reported symptoms of SARS-CoV-2 infection. The virus targets cells for entry by binding of its spike protein to cell-surface angiotensin-converting enzyme- 2 (ACE2). It was not known whether ACE2 is expressed on taste receptor cells (TRCs) nor if TRCs are infected directly. Using an in-situ hybridization (ISH) probe and an antibody specific to ACE2, ACE2 is present on a subpopulation of TRCs, namely, Type II cells in taste buds in taste papillae. Fungiform papillae (FP) of a SARS-CoV-2+ patient exhibiting symptoms of COVID-19, including taste changes, were biopsied. Based on ISH, replicating SARS-CoV-2 was present in Type II cells. Therefore, taste Type II cells provide a potential portal for viral entry that predicts vulnerabilities to SARS-CoV-2 in the oral cavity. The continuity and cell turnover of the patient’s FP taste stem cell layer were disrupted during infection and had not completely recovered 6 weeks post symptom onset. Another patient suffering post-COVID-19 taste disturbances also had disrupted stem cells. These results demonstrate the possibility that novel and sudden taste changes frequently reported in COVID-19 may be the result of direct infection of taste papillae by SARS-CoV-2. This may result in impaired taste receptor stem cell activity and suggest more work is needed to understand the acute and post-acute dynamics of viral kinetics in the human taste bud.

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“…In adults, the reported prevalence of acute neurologic symptoms (e.g., headaches, anosmia, seizure) and conditions (e.g., encephalopathy, stroke, delirium, encephalitis) ranges widely, from 4.4 to 100% of COVID-19 cases [ 10 – 12 ]. Anosmia and dysgeusia, relatively specific manifestations of COVID-19 that affect between 40 and 90% of adult patients, are considered neurologic in origin, although definitive proof is lacking [ 13 – 15 ]. Anosmia occurs in at least 5–20% of pediatric patients [ 16 , 17 ].…”

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confidence: 99%

COVID-19 and the Pediatric Nervous System: Global Collaboration to Meet a Global Need

et al. 2021

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The coronavirus disease 2019 (COVID-19) pandemic has affected mortality and morbidity across all ages, including children. It is now known that neurological manifestations of COVID-19, ranging from headaches to stroke, may involve the central and/or peripheral nervous system at any age. Neurologic involvement is also noted in the multisystem inflammatory syndrome in children, a pediatric condition that occurs weeks after infection with the causative virus of COVID-19, severe acute respiratory syndrome coronavirus 2. Knowledge about mechanisms of neurologic disease is scarce but rapidly growing. COVID-19 neurologic manifestations may have particularly adverse impacts on the developing brain. Emerging data suggest a cohort of patients with COVID-19 will have longitudinal illness affecting their cognitive, physical, and emotional health, but little is known about the long-term impact on affected children and their families. Pediatric collaboratives have begun to provide important initial information on neuroimaging manifestations and the incidence of ischemic stroke in children with COVID 19. The Global Consortium Study of Neurologic Dysfunction in COVID-19-Pediatrics, a multinational collaborative, is working to improve understanding of the epidemiology, mechanisms of neurological manifestations, and the long-term implications of COVID-19 in children and their families.

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Absent Blood Oxygen Level–Dependent Functional Magnetic Resonance Imaging Activation of the Orbitofrontal Cortex in a Patient With Persistent Cacosmia and Cacogeusia After COVID-19 Infection

Cited by 29 publications

References 5 publications

Post-viral effects of COVID-19 in the olfactory system and their implications

Post-viral effects of COVID-19 in the olfactory system and their implications

Human Type II Taste Cells Express Angiotensin-Converting Enzyme 2 and Are Infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

COVID-19 and the Pediatric Nervous System: Global Collaboration to Meet a Global Need

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