PT - JOURNAL ARTICLE AU - Guilherme Dias de Melo AU - Victoire Perraud AU - Flavio Alvarez AU - Alba Vieites-Prado AU - Seonhee Kim AU - Lauriane Kergoat AU - Bettina Salome Trüeb AU - Magali Tichit AU - Aurèle Piazza AU - Agnès Thierry AU - David Hardy AU - Nicolas Wolff AU - Sandie Munier AU - Romain Koszul AU - Etienne Simon-Lorière AU - Volker Thiel AU - Marc Lecuit AU - Pierre-Marie Lledo AU - Nicolas Renier AU - Florence Larrous AU - Hervé Bourhy TI - Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants AID - 10.1101/2022.08.31.505985 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.08.31.505985 4099 - http://biorxiv.org/content/early/2022/08/31/2022.08.31.505985.short 4100 - http://biorxiv.org/content/early/2022/08/31/2022.08.31.505985.full AB - 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. Several studies have focused on the neuropathogenesis of the original SARS-CoV-2, but little is known about the neuropathological potential of the variants. Here, we assessed the clinical, olfactory and inflammatory conditions of golden hamsters infected with the original SARS-CoV-2, its ORF7-deleted mutant, and three variants: Gamma, Delta and Omicron/BA.1. We show that infected animals developed a variant-dependent clinical disease, and that the ORF7 of SARS-CoV-2 contribute to causing olfactory disturbances. Conversely, all SARS-CoV-2 variants were found to be neuroinvasive, regardless of the clinical presentation they induce. With newly-generated nanoluciferase-expressing SARS-CoV-2, we validated the olfactory pathway as a main entry point towards the brain, confirming that neuroinvasion and anosmia are independent phenomena upon SARS-CoV-2 infection.Competing Interest StatementThe authors have declared no competing interest.