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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 1 , Victoire Perraud # 1 , Flavio Alvarez # 2 3 , Alba Vieites-Prado # 4 , Seonhee Kim 1 , Lauriane Kergoat 1 , Anthony Coleon 1 , Bettina Salome Trüeb 5 , Magali Tichit 6 , Aurèle Piazza 7 , Agnès Thierry 7 , David Hardy 6 , Nicolas Wolff 2 , Sandie Munier 8 , Romain Koszul 7 , Etienne Simon-Lorière 9 , Volker Thiel 10 , Marc Lecuit 11 12 , Pierre-Marie Lledo 13 , Nicolas Renier 4 , Florence Larrous 1 , Hervé Bourhy 14
Affiliations
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.
. 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 1 , Victoire Perraud # 1 , Flavio Alvarez # 2 3 , Alba Vieites-Prado # 4 , Seonhee Kim 1 , Lauriane Kergoat 1 , Anthony Coleon 1 , Bettina Salome Trüeb 5 , Magali Tichit 6 , Aurèle Piazza 7 , Agnès Thierry 7 , David Hardy 6 , Nicolas Wolff 2 , Sandie Munier 8 , Romain Koszul 7 , Etienne Simon-Lorière 9 , Volker Thiel 10 , Marc Lecuit 11 12 , Pierre-Marie Lledo 13 , Nicolas Renier 4 , Florence Larrous 1 , Hervé Bourhy 14
Affiliations
- PMID: 37495586
- PMCID: PMC10372078
- DOI: 10.1038/s41467-023-40228-7
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.