Figure 4.

Neuroblast proliferation in the SARS-CoV2 infected hamster and doublecortin (DCX)-positive cells and neurons in human hippocampus from COVID-19 patient and non-COVID-19 control. (A) Microscopy of the dentate gyrus of hamsters at naïve, 2, 3, 4, 5, 8 and 14 dpi, showing staining of Ki67 (red), neuroblast (green) and DAPI (blue), followed by quantification of per cent Ki67⁺DCX⁺ cells, normalized to the total number of DCX⁺ cells. (C) Quantification of per cent DCX⁺Ki67⁺ area, normalized to total DCX⁺ area in the rostral migratory stream of hamsters at naïve, 2, 3, 4, 5, 8 and 14 dpi. Data were pooled from at least two independent experiments. Scale bars = 50 μm. Data represent the mean ± SEM and were analysed by two-way ANOVA. (B) Select images of whole hippocampus and high-magnification images sections stained with DAPI (blue), NeuN (green) and DCX (red) from COVID-19 patient and non-COVID-19 control. The granule cell layer (GCL), subgranular zone (SGZ) and molecular layer (ML) of the dentate gyrus are visible, combined channels imaged at ×20; scale bar = 500 μm. High-magnification images were captured at ×63, scale bar = 20 μm. (D) In the SGZ, DCX⁺/NeuN⁻ cells were fewer in COVID-19 patients versus controls [P = 0.026; t(7.794) = 2.731; Welch’s t-test for non-stoichiometric data], with no group differences in DCX⁺/NeuN⁺ cell number (P = 0.189; Mann–Whitney). In the GCL, neither DCX⁺/NeuN⁻ cell count (P = 0.846; Mann–Whitney) nor DCX⁺/NeuN⁺ cell count (P = 0.378; Mann–Whitney) differs between COVID-19 and control subjects. Per cent of DCX⁺/NeuN⁻ cells located in the SGZ versus the GCL did not differ between control and COVID-19 groups (P = 0.453; Mann–Whitney). Per cent of DCX⁺/NeuN⁺ cells located in the GCL versus the SGZ was lower in COVID-19 patients versus control subjects (P = 0.009; Mann–Whitney).