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Nat Commun . Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants

tetano

Editor, Senior Moderator
Nat Commun


. 2023 Jul 26;14(1):4485.
doi: 10.1038/s41467-023-40228-7. Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants

Guilherme Dias de Melo[SUP] 1 [/SUP], Victoire Perraud[SUP] #[/SUP][SUP] 1 [/SUP], Flavio Alvarez[SUP] #[/SUP][SUP] 2 3 [/SUP], Alba Vieites-Prado[SUP] #[/SUP][SUP] 4 [/SUP], Seonhee Kim[SUP] 1 [/SUP], Lauriane Kergoat[SUP] 1 [/SUP], Anthony Coleon[SUP] 1 [/SUP], Bettina Salome Trüeb[SUP] 5 [/SUP], Magali Tichit[SUP] 6 [/SUP], Aurèle Piazza[SUP] 7 [/SUP], Agnès Thierry[SUP] 7 [/SUP], David Hardy[SUP] 6 [/SUP], Nicolas Wolff[SUP] 2 [/SUP], Sandie Munier[SUP] 8 [/SUP], Romain Koszul[SUP] 7 [/SUP], Etienne Simon-Lorière[SUP] 9 [/SUP], Volker Thiel[SUP] 10 [/SUP], Marc Lecuit[SUP] 11 12 [/SUP], Pierre-Marie Lledo[SUP] 13 [/SUP], Nicolas Renier[SUP] 4 [/SUP], Florence Larrous[SUP] 1 [/SUP], Hervé Bourhy[SUP] 14 [/SUP]



Affiliations
Abstract

Anosmia was identified as a hallmark of COVID-19 early in the pandemic, however, with the emergence of variants of concern, the clinical profile induced by SARS-CoV-2 infection has changed, with anosmia being less frequent. Here, we assessed the clinical, olfactory and neuroinflammatory conditions of golden hamsters infected with the original Wuhan SARS-CoV-2 strain, its isogenic ORF7-deletion mutant and three variants: Gamma, Delta, and Omicron/BA.1. We show that infected animals develop a variant-dependent clinical disease including anosmia, and that the ORF7 of SARS-CoV-2 contributes to the induction of olfactory dysfunction. Conversely, all SARS-CoV-2 variants are neuroinvasive, regardless of the clinical presentation they induce. Taken together, this confirms that neuroinvasion and anosmia are independent phenomena upon SARS-CoV-2 infection. Using newly generated nanoluciferase-expressing SARS-CoV-2, we validate the olfactory pathway as a major entry point into the brain in vivo and demonstrate in vitro that SARS-CoV-2 travels retrogradely and anterogradely along axons in microfluidic neuron-epithelial networks.


 
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