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

Autor: Sánchez-Morales L; VISAVET Health Surveillance Centre, Complutense University of Madrid, 28040, Madrid, Spain.; Department of Animal Health, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040, Madrid, Spain., Porras N; VISAVET Health Surveillance Centre, Complutense University of Madrid, 28040, Madrid, Spain., García-Seco T; VISAVET Health Surveillance Centre, Complutense University of Madrid, 28040, Madrid, Spain., Pérez-Sancho M; VISAVET Health Surveillance Centre, Complutense University of Madrid, 28040, Madrid, Spain. maperezs@ucm.es.; Department of Animal Health, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040, Madrid, Spain. maperezs@ucm.es., Cruz F; VISAVET Health Surveillance Centre, Complutense University of Madrid, 28040, Madrid, Spain., Chinchilla B; VISAVET Health Surveillance Centre, Complutense University of Madrid, 28040, Madrid, Spain.; Department of Animal Production, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040, Madrid, Spain., Barroso-Arévalo S; VISAVET Health Surveillance Centre, Complutense University of Madrid, 28040, Madrid, Spain.; Department of Animal Health, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040, Madrid, Spain., Diaz-Frutos M; VISAVET Health Surveillance Centre, Complutense University of Madrid, 28040, Madrid, Spain.; Department of Animal Health, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040, Madrid, Spain., Buendía A; VISAVET Health Surveillance Centre, Complutense University of Madrid, 28040, Madrid, Spain., Moreno I; Unidad de Inmunología Microbiana, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Pozuelo-Majadahonda km 2, Majadahonda, 28220, Madrid, Spain., Briones V; VISAVET Health Surveillance Centre, Complutense University of Madrid, 28040, Madrid, Spain.; Department of Animal Health, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040, Madrid, Spain., Risalde MLÁ; Departamento de Anatomía y Anatomía Patológica Comparadas y Toxicología, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), UIC Zoonosis y Enfermedades Emergentes (ENZOEM), Universidad de Córdoba, Córdoba, Spain., de la Fuente J; SaBio Instituto de Investigación en Recursos Cinegéticos, Ciudad Real, Spain.; Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA., Juste R; Animal Health Department, NEIKER-Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), 48160, Derio, Bizkaia, Spain., Garrido J; Animal Health Department, NEIKER-Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), 48160, Derio, Bizkaia, Spain., Balseiro A; Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad de León, 24071, León, Spain., Gortázar C; SaBio Instituto de Investigación en Recursos Cinegéticos, Ciudad Real, Spain., Rodríguez-Bertos A; VISAVET Health Surveillance Centre, Complutense University of Madrid, 28040, Madrid, Spain.; Department of Internal Medicine and Animal Surgery, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040, Madrid, Spain., Domínguez M; Unidad de Inmunología Microbiana, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Pozuelo-Majadahonda km 2, Majadahonda, 28220, Madrid, Spain., Domínguez L; VISAVET Health Surveillance Centre, Complutense University of Madrid, 28040, Madrid, Spain.; Department of Animal Health, Faculty of Veterinary Medicine, Complutense University of Madrid, 28040, Madrid, Spain.; Real Academia de Doctores de España, C. de San Bernardo, 49, 28015, Madrid, Spain.
Jazyk: angličtina
Zdroj: Veterinary research [Vet Res] 2024 May 31; Vol. 55 (1), pp. 71. Date of Electronic Publication: 2024 May 31.
DOI: 10.1186/s13567-024-01325-7
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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