RT Journal Article SR Electronic T1 Neuroinvasion and anosmia are independent phenomena upon infection with SARS-CoV-2 and its variants JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.08.31.505985 DO 10.1101/2022.08.31.505985 A1 Guilherme Dias de Melo A1 Victoire Perraud A1 Flavio Alvarez A1 Alba Vieites-Prado A1 Seonhee Kim A1 Lauriane Kergoat A1 Bettina Salome Trüeb A1 Magali Tichit A1 Aurèle Piazza A1 Agnès Thierry A1 David Hardy A1 Nicolas Wolff A1 Sandie Munier A1 Romain Koszul A1 Etienne Simon-Lorière A1 Volker Thiel A1 Marc Lecuit A1 Pierre-Marie Lledo A1 Nicolas Renier A1 Florence Larrous A1 Hervé Bourhy YR 2022 UL http://biorxiv.org/content/early/2022/08/31/2022.08.31.505985.abstract 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.