COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters

Guilherme Dias de Melo (1) , Françoise Lazarini (2) , Sylvain Levallois (3) , Charlotte Hautefort (4, 5) , Vincent Michel (2, 6) , Florence Larrous (1) , Benjamin Verillaud (4, 5) , Caroline Aparicio (7) , Sebastien Wagner (2) , Gilles Gheusi (2, 8) , Lauriane Kergoat (1) , Etienne Kornobis (9, 10) , Flora Donati (11, 12) , Thomas Cokelaer (10, 9) , Rémi Hervochon (13) , Yoann Madec (14) , Emmanuel Roze (15) , Dominique Salmon (16, 5) , Hervé Bourhy (1) , Marc Lecuit (3, 17) , Pierre-Marie Lledo (2)

1 Lyssavirus, épidémiologie et neuropathologie - Lyssavirus Epidemiology and Neuropathology
2 Perception et Mémoire / Perception and Memory
3 Biologie des Infections - Biology of Infection
4 Service d'oto-rhino-laryngologie
5 UPCité - Université Paris Cité
6 IDA - Institut de l'Audition [Paris]
7 Hôpital Lariboisière-Fernand-Widal [APHP]
8 LEEC - Laboratoire d'Ethologie Expérimentale et Comparée
9 Biomics (plateforme technologique)
10 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
11 CNR - laboratoire coordonnateur - Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris]
12 GMV-ARN (UMR_3569 / U-Pasteur_2) - Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses
13 CHU Pitié-Salpêtrière [AP-HP]
14 Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology
15 ICM - Institut du Cerveau = Paris Brain Institute
16 Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin]
17 Service des Maladies infectieuses et tropicales [CHU Necker]

Whereas recent investigations have revealed viral, inflammatory and vascular factors involved in SARS-CoV-2 lung pathogenesis, the pathophysiology of neurological disorders in 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 may be 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. Finally, 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.

Domaines: Sciences du Vivant [q-bio]; Virologie

Guilherme Dias de Melo, Françoise Lazarini, Sylvain Levallois, Charlotte Hautefort, Vincent Michel, et al.. COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters. Science Translational Medicine, 2021, pp.eabf8396. ⟨10.1126/scitranslmed.abf8396⟩. ⟨pasteur-03242618⟩