Fig. 1

Omicron BA.1 has impaired neurovirulence and neurotropism compared to Delta and D614G. Human induced pluripotent stem cell-derived neural co-cultures consisting of cortical neurons and astrocytes were inoculated with the D164G, Delta and Omicron BA.1 variant at MOI 0.5. A Growth kinetics of D164G, Delta and Omicron BA.1. Growth curves were performed three independent times, once in biological duplicates and two times in biological triplicates. B Neural co-cultures were fixed at 24 h post infection. To investigate the cellular tropism co-cultures were stained with microtubule-associated protein (MAP2, cyan) as a marker for neurons, astrocytes were identified by staining for glial fibrillary acidic protein (GFAP) (green), and SARS-CoV-2 nucleoprotein (magenta) was used to identify infected cells. Cells were counterstained with Hoechst (grey) to visualize the nuclei. Data shown are representative examples from three independent experiments. C Percentage of SARS-CoV-2 infected MAP2⁺ neurons was calculated with flow cytometry at 24 and 72 h post infection. Data represent mean ± standard deviation (SD) from two independent experiments performed in biological triplicates. D Protein concentrations of IFN-λ2/3, IP-10 and IL-8 were measured in the supernatants of SARS-CoV-2 infected neural co-cultures with a multiplexed bead assay. The data are derived from three independent experiments, and each experiment was performed in biological triplicates. Statistical significance in C and D was calculated with a one-way analysis of variance (ANOVA) with a Bonferroni post hoc test, and the means from the mock-infected samples were compared to the means from the SARS-CoV-2 infected samples at 24 and 72 h post infection. Asterisks indicate statistical significance: *P < 0.05, **, P < 0.01, ***P < 0.001, ****P < 0.0001)