SARS-CoV-2 omicron BA.5 and XBB variants have increased neurotropic potential over BA.1 in K18-hACE2 mice and human brain organoids

• DOI: 10.3389/fmicb.2023.1320856
• Publication Date: 2023-11-23T11:31:11Z
• Authors: Romal Stewart; Kexin Yan; Sevannah A. Ellis; Cameron R. Bishop; Troy Dumenil; Bing Tang; Wilson Nguyen; Thibaut Larcher; Rhys Parry; Julian De Jun Sng; Alexander A. Khro...; Robert K. P. Sull...; Mary Lor; Frédéric A. Meunier; Daniel J. Rawle; Andreas Suhrbier
• Keywords: Organoid; Human brain; Lineage (genetic)

The reduced pathogenicity of the omicron BA.1 sub-lineage compared to earlier variants is well described, although whether such attenuation retained for later like BA.5 and XBB remains controversial. We show that isolates were significantly more pathogenic in K18-hACE2 mice than a isolate, showing increased neurotropic potential, resulting fulminant brain infection mortality, similar seen original ancestral isolates. also infected human cortical organoids greater extent In brains mice, neurons main target infection, neuronal progenitor cells immature infected. results herein suggest evolving may have increasing potential.