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Post-viral effects of COVID-19 in the olfactory system and their implications.
Xydakis, Michael S; Albers, Mark W; Holbrook, Eric H; Lyon, Dina M; Shih, Robert Y; Frasnelli, Johannes A; Pagenstecher, Axel; Kupke, Alexandra; Enquist, Lynn W; Perlman, Stanley.
  • Xydakis MS; Human Performance Wing, Air Force Research Lab, US Department of Defense, Wright-Patterson Air Force Base, Dayton, OH, USA. Electronic address: michael.xydakis@gmail.com.
  • Albers MW; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • Holbrook EH; Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.
  • Lyon DM; Human Performance Wing, Air Force Research Lab, US Department of Defense, Wright-Patterson Air Force Base, Dayton, OH, USA.
  • Shih RY; Division of Neuroradiology, Walter Reed National Military Medical Center, US Department of Defense, Bethesda, MD, USA.
  • Frasnelli JA; Department of Anatomy, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada.
  • Pagenstecher A; Department of Neuropathology, Philipps University of Marburg, Marburg, Germany.
  • Kupke A; Marburg Virology Institute, Philipps University of Marburg, Marburg, Germany.
  • Enquist LW; Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.
  • Perlman S; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, USA.
Lancet Neurol ; 20(9): 753-761, 2021 09.
Article in English | MEDLINE | ID: covidwho-1599333
ABSTRACT

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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Olfactory Mucosa / COVID-19 / Olfaction Disorders Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Topics: Long Covid Limits: Humans Language: English Journal: Lancet Neurol Journal subject: Neurology Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Olfactory Mucosa / COVID-19 / Olfaction Disorders Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Topics: Long Covid Limits: Humans Language: English Journal: Lancet Neurol Journal subject: Neurology Year: 2021 Document Type: Article