PT  - JOURNAL ARTICLE
AU  - Guilherme Dias De Melo
AU  - Françoise Lazarini
AU  - Sylvain Levallois
AU  - Charlotte Hautefort
AU  - Vincent Michel
AU  - Florence Larrous
AU  - Benjamin Verillaud
AU  - Caroline Aparicio
AU  - Sebastien Wagner
AU  - Gilles Gheusi
AU  - Lauriane Kergoat
AU  - Etienne Kornobis
AU  - Thomas Cokelaer
AU  - Rémi Hervochon
AU  - Yoann Madec
AU  - Emmanuel Roze
AU  - Dominique Salmon
AU  - Hervé Bourhy
AU  - Marc Lecuit
AU  - Pierre-Marie Lledo
TI  - COVID-19-associated olfactory dysfunction reveals SARS-CoV-2 neuroinvasion and persistence in the olfactory system
AID  - 10.1101/2020.11.18.388819
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.18.388819
4099  - http://biorxiv.org/content/early/2020/11/18/2020.11.18.388819.short
4100  - http://biorxiv.org/content/early/2020/11/18/2020.11.18.388819.full
AB  - While 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. Yet, olfactory and taste dysfunction are rather common in COVID-19, especially in pauci-symptomatic patients which constitutes the most frequent clinical manifestation of the infection. We conducted a virologic, molecular, and cellular study of the olfactory system from COVID-19 patients presenting acute loss of smell, and report evidence that the olfactory epithelium represents a highly significant infection site where multiple cell types, including olfactory sensory neurons, support cells and immune cells, are infected. Viral replication in the olfactory epithelium is associated with local inflammation. Furthermore, we show that SARS-CoV-2 induces acute anosmia and ageusia in golden Syrian hamsters, both lasting as long as the virus remains in the olfactory epithelium and the olfactory bulb. Finally, olfactory mucosa sampling in COVID-19 patients presenting with persistent loss of smell reveals the presence of virus transcripts and of SARS-CoV-2-infected cells, together with protracted inflammation. Viral persistence in the olfactory epithelium therefore provides a potential mechanism for prolonged or relapsing symptoms of COVID-19, such as loss of smell, which should be considered for optimal medical management and future therapeutic strategies.Competing Interest StatementThe authors have declared no competing interest.