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COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters.
de Melo, Guilherme Dias; Lazarini, Françoise; Levallois, Sylvain; Hautefort, Charlotte; Michel, Vincent; Larrous, Florence; Verillaud, Benjamin; Aparicio, Caroline; Wagner, Sebastien; Gheusi, Gilles; Kergoat, Lauriane; Kornobis, Etienne; Donati, Flora; Cokelaer, Thomas; Hervochon, Rémi; Madec, Yoann; Roze, Emmanuel; Salmon, Dominique; Bourhy, Hervé; Lecuit, Marc; Lledo, Pierre-Marie.
  • de Melo GD; Lyssavirus Epidemiology and Neuropathology Unit, Institut Pasteur, 75015 Paris, France.
  • Lazarini F; Perception and Memory Unit, Institut Pasteur, CNRS UMR3571, 75015 Paris, France.
  • Levallois S; Biology of Infection Unit, Institut Pasteur, 75015 Paris, France.
  • Hautefort C; INSERM U1117, 75015 Paris, France.
  • Michel V; Otolaryngology-Head and Neck Surgery Department, Hopital Lariboisiere, Assistance Publique-Hôpitaux de Paris, INSERM U1141, Université de Paris, 75010 Paris, France.
  • Larrous F; Perception and Memory Unit, Institut Pasteur, CNRS UMR3571, 75015 Paris, France.
  • Verillaud B; Institut de l'Audition, Institut Pasteur, Paris, France.
  • Aparicio C; INSERM U1120, 75012 Paris, France.
  • Wagner S; Lyssavirus Epidemiology and Neuropathology Unit, Institut Pasteur, 75015 Paris, France.
  • Gheusi G; Otolaryngology-Head and Neck Surgery Department, Hopital Lariboisiere, Assistance Publique-Hôpitaux de Paris, INSERM U1141, Université de Paris, 75010 Paris, France.
  • Kergoat L; Emergency Department, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Université de Paris, 75010 Paris, France.
  • Kornobis E; Perception and Memory Unit, Institut Pasteur, CNRS UMR3571, 75015 Paris, France.
  • Donati F; Perception and Memory Unit, Institut Pasteur, CNRS UMR3571, 75015 Paris, France.
  • Cokelaer T; Laboratory of Experimental and Comparative Ethology, Université Sorbonne Paris Nord, Villetaneuse, France.
  • Hervochon R; Lyssavirus Epidemiology and Neuropathology Unit, Institut Pasteur, 75015 Paris, France.
  • Madec Y; Plateforme Technologique Biomics-Centre de Ressources et Recherches Technologiques (C2RT), Institut Pasteur, 75015 Paris, France.
  • Roze E; Hub de Bioinformatique et Biostatistique-Département Biologie Computationnelle, Institut Pasteur, USR 3756 CNRS, 75015 Paris, France.
  • Salmon D; National Reference Center for Respiratory Viruses, Institut Pasteur, 75015 Paris, France.
  • Bourhy H; Molecular Genetics of RNA Viruses, CNRS UMR3569, University of Paris, Institut Pasteur, 75015 Paris, France.
  • Lecuit M; Plateforme Technologique Biomics-Centre de Ressources et Recherches Technologiques (C2RT), Institut Pasteur, 75015 Paris, France.
  • Lledo PM; Hub de Bioinformatique et Biostatistique-Département Biologie Computationnelle, Institut Pasteur, USR 3756 CNRS, 75015 Paris, France.
Sci Transl Med ; 13(596)2021 06 02.
Article in English | MEDLINE | ID: covidwho-1214961
ABSTRACT
Whereas recent investigations have revealed viral, inflammatory, and vascular factors involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung pathogenesis, the pathophysiology of neurological disorders in coronavirus disease 2019 (COVID-19) remains poorly understood. Olfactory and taste dysfunction are common in COVID-19, especially in mildly symptomatic patients. Here, we conducted a virologic, molecular, and cellular study of the olfactory neuroepithelium of seven patients with COVID-19 presenting with acute loss of smell. We report evidence that the olfactory neuroepithelium is a major site of SARS-CoV2 infection with multiple cell types, including olfactory sensory neurons, support cells, and immune cells, becoming infected. SARS-CoV-2 replication in the olfactory neuroepithelium was associated with local inflammation. Furthermore, we showed that SARS-CoV-2 induced acute anosmia and ageusia in golden Syrian hamsters, lasting as long as the virus remained in the olfactory epithelium and the olfactory bulb. Last, olfactory mucosa sampling from patients showing long-term persistence of COVID-19-associated anosmia revealed the presence of virus transcripts and of SARS-CoV-2-infected cells, together with protracted inflammation. SARS-CoV-2 persistence and associated inflammation in the olfactory neuroepithelium may account for prolonged or relapsing symptoms of COVID-19, such as loss of smell, which should be considered for optimal medical management of this disease.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Brain / Olfactory Mucosa / Anosmia / COVID-19 Topics: Long Covid Limits: Animals / Humans Language: English Journal subject: Science / Medicine Year: 2021 Document Type: Article Affiliation country: Scitranslmed.abf8396

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Brain / Olfactory Mucosa / Anosmia / COVID-19 Topics: Long Covid Limits: Animals / Humans Language: English Journal subject: Science / Medicine Year: 2021 Document Type: Article Affiliation country: Scitranslmed.abf8396