Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2
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Published:2024-05-31
Issue:1
Volume:55
Page:
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ISSN:1297-9716
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Container-title:Veterinary Research
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language:en
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Short-container-title:Vet Res
Author:
Sánchez-Morales Lidia, Porras Néstor, García-Seco Teresa, Pérez-Sancho MartaORCID, Cruz Fátima, Chinchilla Blanca, Barroso-Arévalo Sandra, Diaz-Frutos Marta, Buendía Aránzazu, Moreno Inmaculada, Briones Víctor, Risalde María de los Ángeles, de la Fuente José, Juste Ramón, Garrido Joseba, Balseiro Ana, Gortázar Christian, Rodríguez-Bertos Antonio, Domínguez Mercedes, Domínguez Lucas
Abstract
AbstractIn 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.
Funder
Comunidad de Madrid Ministerio de Ciencia e Innovación
Publisher
Springer Science and Business Media LLC
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