Additional file 1. Representation of clinical scores of infected animals at the day of sacrifice and viral loads (brain, lung, trachea/nasal turbinates) from both groups.
*The clinical score from this animal could not be recorded because it was found dead at 7 dpi. **These scores correspond to the day on which the animals were euthanized which coincided with the day of the highest clinical score.

Additional file 2. Detailed histological score of the animals from both groups for the different brain sections.
Sections analysed are: olfactory bulb, pyriform cortex, septum-striatum, cerebral cortex, hippocampus, thalamus, hypothalamus, caudal mesencephalon, pons, cerebellum, and spinal cord scoring each lesion from 0 to 5.

Additional file 3. Detailed neuronal immunoexpresion score of the animals from both groups for the different brain sections.
Immunoexpresion was scored from 0 to 5 according to their degree of extension, based on the proportion of affected neurons.

Additional file 4. Brain lesions and SARS-CoV-2 IHC observed in SARS-CoV-2 (A, C, E, G, I, K, M, O) and BCG-SARS-CoV-2 (B, D, F, H, J, K, L, N, P) at 7 dpi.
These analyses were performed in specific areas like orbital cerebral cortex (precentral area) (A, B), septum (C, D), pyriform cortex (E, F), olfactory tubercle (G, H), cerebral cortex (postcentral area) (I, J), thalamus (K, L), mesencephalon (M, N) and pons (O, P). Histopathological study revealed more severe lesions in the BCG-stimulated animals, highlighting perivascular lymphocytic cuffings, increase in glial cell population (mainly microglia) and neuronal degeneration, characterized by red neurons and cytoplasmic ballooning; H&E, 10×. IHC of SARS-CoV-2 (insets) revealed a higher number of infected neurons in non-stimulated group at 7 dpi; IHC, 20×.

Additional file 5. Main microscopic changes observed in the lungs of BCG-SARS-CoV-2 mice at 5–8 days post SARS-COV-2 infection. (A) Perivascular and peribronchiolar mononuclear cell infiltration, hyperplasia of the bronchiolar epithelium and foci of pleuritis; H&E, 10×. (B) Vascular thrombosis; H&E, 20×. (C) Abundant foamy macrophages in the alveolar interstitium; H&E, 40×. (D) Desquamative alveolitis; H&E, 40×.

Additional file 6. IHC evaluation (CD3, PAX5, Iba-1) in brain (A, B, C) and lungs (D, E, F) of BCG-SARS-CoV-2 mice at 5–8 days post-infection. (A) CD3+ T cells immunoexpression in lymphocytic perivascular cuffings (arrowhead); anti-CD3, 40×. (B) No presence of PAX5+ B cells immunoexpression in lymphocytic perivascular cuffings; anti-PAX5, 40×. (arrowhead). (C) Iba-1+ microglial cells immunoexpression surrounding lymphocytic perivascular cuffings (arrowhead); anti-Iba-1, 20×. (D) CD3+ T cells immunoexpression in lymphocytic perivascular cuffings and alveolar interstitium (arrowhead); anti-CD3, 40×. (E) Minimal presence of PAX5+ B cells immunoexpression in lymphocytic perivascular cuffings; anti-PAX5, 40×. (arrowhead). (F) Iba-1+ macrophages immunoexpression in pulmonar interstitium (arrowhead); anti-Iba-1, 20×. Inset: Iba-1+ foamy macrophages immunoexpression in alveolar interstitium; anti-Iba-1, 40×.