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Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2

Investigation article published in Veterinary Research

May 31st, 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. and Dominguez L..




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Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2

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Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2



Participants:

Universidad ComplutenseServicio de Identificación y Caracterización Microbiana (ICM). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).

Universidad ComplutenseDepartamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM).

Universidad ComplutenseDepartamento de Producción Animal. Facultad de Veterinaria. Universidad Complutense (UCM).

Instituto de Salud Carlos IIIServicio de Inmunología. Centro Nacional de Microbiología (CNM). Instituto de Salud Carlos III (ISCIII).

Universidad de CórdobaDepartamento de Anatomía y Anatomía Patológica Comparadas. Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad de Córdoba (UCO).

Gobierno de Castilla-La ManchaSanidad 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).

Oklahoma State UniversityDepartament of Veterinary Pathobiology. Center for Veterinary Health Sciences (CVHS). Oklahoma State University (OSU).

Basque Research and Technology Alliance (BRTA).

Gobierno VascoInstituto Vasco de Investigación y Desarrollo Agrario (NEIKER). Gobierno Vasco.

Universidad de LeónDepartamento de Sanidad Animal. Facultad de Veterinaria. Universidad de León.

Universidad ComplutenseDepartamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM).

Real Academia de Doctores de EspañaReal Academia de Doctores de España (RADE).







Veterinary Research
FACTOR YEAR Q
4.400 2022

NLMID: 9309551

PMID: 38822398

ISSN: 0928-4249



TITLE: Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2


JOURNAL: Vet Res


NUMERACIÓN: 55(1):71


AÑO: 2024


PUBLISHER: BMC


AUTHORS: 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. and Dominguez L..


First
Lidia Sánchez Morales
2nd
Néstor Porras González
3rd
María Teresa García-Seco Romero
4th
Marta Pérez Sancho
5th
Fátima Cruz López
6th
Blanca Chinchilla Rodríguez
7th
Sandra Barroso Arévalo
9th
Aránzazu Buendía Andrés
10
Inmaculada Moreno Iruela
11th
Víctor Briones Dieste
13th
José de Jesús de la Fuente García
17th
Christian Gortazar Schmidt
18th
Antonio Manuel Rodríguez Bertos
19th
Mercedes Domínguez Rodríguez
Last
Lucas Domínguez Rodríguez

DOI: https://doi.org/10.1186/s13567-024-01325-7


CITE THIS PUBLICATION:

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. and Dominguez L. Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2. Veterinary Research. 55(1):71. 2024. (A). ISSN: 0928-4249. DOI: 10.1186/s13567-024-01325-7


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