Fig. 5: Reduced blood oxygen may contribute to brain hypoxia in SARS-CoV-2 infection.

SARS-CoV-2 infection was associated with lower blood oxygen levels (a) and increased blood carbon dioxide (b). Yellow shading denotes a lower than physiological range of SpO₂. HIF-1a expression appeared to be upregulated by cells comprising the vasculature and extended into the parenchyma in the context of infection. Expression was significantly greater than age-matched mock-infected control animals in (c) brainstem, *p = 0.0154 (95% CI = 0.06550–0.4895) control vs. infected animals and (d) basal ganglia, **p = 0.0016 (95%CI = 0.1149 to 0.3621) control vs. infected animals. Significant difference was not seen in (e) cerebellum (n = 4 biologically independent samples in the control group, and n = 8 biologically independent samples in the infected group). Statistics were performed with unpaired two-tailed t test, df = 10. Data are expressed as mean ± SEM. When separated by species, statistical significance is retained in the basal ganglia but not brainstem (Supplementary Data Fig. 7). Representative images show low HIF-1α expression in brainstem of mock-infected animals, RM5 (f) and AGM5 (h), as well as basal ganglia of RM6 (j) and AGM5 (l). In comparison, HIF-1a is upregulated in brain of infected animals. Representative images include brainstem of RM3 (g) and AGM4 (i) and basal ganglia of RM3 (k) and AGM1 (m). Immunohistochemical staining for HIF-1α was performed thrice on the brain regions investigated. Source data are provided as a Source Data file. Abbreviations: PI post-infection. O.D. optical density, %SpO₂ blood oxygen saturation, AGM African green monkey, RM Rhesus macaque, C control, I infected. Scale bars = 50 µm.