A groundbreaking study conducted by the QIMR Berghofer Medical Research Institute, University of Queensland, and the Australian Infectious Disease Research Centre has shed new light on the neurotropic potential of the omicron variants BA.5 and XBB. The study aimed to gain a better understanding of the pathogenicity of these variants, particularly in relation to the nervous system.
The omicron lineage has rapidly spread globally, raising questions about its evolutionary origins and the specific neurological manifestations associated with BA.5 and XBB. To address these challenges, the researchers utilized the K18-hACE2 mouse model and human cortical brain organoids to study the neurotropic potential of these variants.
The study findings revealed that BA.5 and XBB have a higher neurotropic potential than previously thought. This challenges the assumption that the attenuation observed in earlier omicron variants persists. The researchers observed an increased pathogenicity of BA.5 and XBB in the K18-hACE2 mouse model, leading to fulminant brain infection and increased mortality. Additionally, the capacity of BA.5 to infect human cortical brain organoids was found to be greater than that of its predecessor, BA.1, suggesting an escalating neurotropic potential in evolving omicron variants.
Histological examinations of BA.5 and XBB-infected mouse brains revealed lesions similar to those found in post-mortem COVID-19 patient brains. This indicates potential similarities in neuropathology between the variants and severe cases of COVID-19. RNA-Seq analysis of BA.5-infected mouse brains further revealed a cytokine storm characterized by the upregulation of interferons, TNF, IL-1, and IL-6. Comparative analysis with severe COVID-19 patients showed shared inflammatory pathways and cytokine responses, highlighting the similarities between the two species.
These findings have significant implications for understanding the impact of the omicron variants on human health, particularly in relation to the nervous system. The study underscores the importance of continued vigilance and research in order to develop targeted interventions and mitigate potential neurological complications associated with emerging variants. Understanding the evolving dynamics of the virus and its interactions with the nervous system is crucial in the ongoing fight against the COVID-19 pandemic.