Delta (B1.617.2) variant of SARS-CoV-2 induces severe neurotropic patterns in K18-hACE2 mice

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly contagious virus, emerged and quickly spread globally, resulting in the coronavirus disease 19 (COVID-19) pandemic. Genetic variants of SARS-CoV-2 have been reported to circulate throughout the COVID-19 pandemic. The major symptoms of COVID-19 are respiratory symptoms, fever, muscle pain, and breathing difficulty. In addition, up to 30% of patients with COVID-19 complain of neurological complications such as headache, nausea, stroke, and anosmia. However, the neurotropism of SARS-CoV-2 infection remains largely unknown. This study investigated neurotropic patterns between the B1.617.2 (Delta) and Hu-1 variants (Wuhan, early strain) in K18-hACE2 mice. B1.617.2-infected K18-hACE2 mice displayed massive weight loss, greater lethality, and severe conjunctivitis compared to the findings Hu-1–infected mice despite their similar pathogenic patterns in various organs. Additionally, we demonstrated through histopathological analysis that B1.617.2 more readily infects the brain than the lungs and infects the brain earlier after inoculation. Finally, we found that the upregulation of various signature genes involved in type I interferon- and cytokine-mediated signaling was most pronounced after B1.617.2 infection, and a small population of cells exhibited necrosis-related responses. This study has provided helpful information for potential treatment strategies.