Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2
Artículo de investigación publicado en Veterinary Research
31 de mayo de 2024
In the wake of the COVID-19 pandemic caused by SARS-CoV-2, questions emerged about the potential effects of Bacillus Calmette-Guérin (BCG) vaccine on the immune response to SARS-CoV-2 infection, including the neurodegenerative diseases it may contribute to. To explore this, an experimental study was carried out in BCG-stimulated and non-stimulated k18-hACE2 mice challenged with SARS-CoV-2. Viral loads in tissues determined by RT-qPCR, histopathology in brain and lungs, immunohistochemical study in brain (IHC) as well as mortality rates, clinical signs and plasma inflammatory and coagulation biomarkers were assessed. Our results showed BCG-SARS-CoV-2 challenged mice presented higher viral loads in the brain and an increased frequency of neuroinvasion, with the greatest differences observed between groups at 3-4 days post-infection (dpi). Histopathological examination showed a higher severity of brain lesions in BCG-SARS-CoV-2 challenged mice, mainly consisting of neuroinflammation, increased glial cell population and neuronal degeneration, from 5 dpi onwards. This group also presented higher interstitial pneumonia and vascular thrombosis in lungs (3-4 dpi), BCG-SARS-CoV-2 mice showed higher values for TNF-α and D-dimer values, while iNOS values were higher in SARS-CoV-2 mice at 3-4 dpi. Results presented in this study indicate that BCG stimulation could have intensified the inflammatory and neurodegenerative lesions promoting virus neuroinvasion and dissemination in this experimental model. Although k18-hACE2 mice show higher hACE2 expression and neurodissemination, this study suggests that, although the benefits of BCG on enhancing heterologous protection against pathogens and tumour cells have been broadly demonstrated, potential adverse outcomes due to the non-specific effects of BCG should be considered
Sánchez-Morales L., Porras N., Garcia-Seco T., Perez-Sancho M., Cruz F., Chinchilla-Rodríguez B., Barroso-Arevalo S., Diaz-de Frutos M., Buendia A., Moreno I., Briones V., Risalde MA., de la Fuente J., Juste R., Garrido J., Balseiro A., Gortazar C., Rodriguez-Bertos A., Dominguez M. y Dominguez L..
 | Servicio de Identificación y Caracterización Microbiana (ICM). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM). |
| Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM). |
| Departamento de Producción Animal. Facultad de Veterinaria. Universidad Complutense (UCM). |
 | Servicio de Inmunología. Centro Nacional de Microbiología (CNM). Instituto de Salud Carlos III (ISCIII). |
 | Departamento de Anatomía y Anatomía Patológica Comparadas. Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad de Córdoba (UCO). |
 | Sanidad y Biotecnología (SaBio). Instituto de Investigación en Recursos Cinegéticos (IREC). Consejo Superior de Investigaciones Científicas (CSIC). Universidad de Castilla La Mancha (UCLM). Gobierno de Castilla-La Mancha (JCCM). |
 | Departament of Veterinary Pathobiology. Center for Veterinary Health Sciences (CVHS). Oklahoma State University (OSU). |
| Basque Research and Technology Alliance (BRTA). | |
 | Instituto Vasco de Investigación y Desarrollo Agrario (NEIKER). Gobierno Vasco. |
 | Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad de León. |
| Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM). |
 | Real Academia de Doctores de España (RADE). |
