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

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. 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. Graphical asbtract O_FIG O_LINKSMALLFIG WIDTH=150 HEIGHT=200 SRC="FIGDIR/small/505985v1_ufig1.gif" ALT="Figure 1"> View larger version (49K) org.highwire.dtl.DTLVardef@1dd3fd3org.highwire.dtl.DTLVardef@896aeaorg.highwire.dtl.DTLVardef@1ca6157org.highwire.dtl.DTLVardef@1bcd84c_HPS_FORMAT_FIGEXP M_FIG C_FIG