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

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dc.contributor.authorSánchez Morales, Lidia
dc.contributor.authorPorras González, Néstor
dc.contributor.authorGarcía-Seco Romero, María Teresa
dc.contributor.authorPérez Sancho, Marta
dc.contributor.authorCruz López, Fátima
dc.contributor.authorChinchilla Rodríguez, Blanca
dc.contributor.authorBarroso Arévalo, Sandra
dc.contributor.authorDíaz Frutos, Marta
dc.contributor.authorBuendía Andrés, Aránzazu
dc.contributor.authorMoreno, Inmaculada
dc.contributor.authorBriones Dieste, Víctor
dc.contributor.authorRisalde, María A.
dc.contributor.authorDe la Fuente, José
dc.contributor.authorJuste, Ramón
dc.contributor.authorGarrido, Joseba
dc.contributor.authorBalseiro, Ana
dc.contributor.authorGortázar, Christian
dc.contributor.authorRodríguez Bertos, Antonio Manuel
dc.contributor.authorDomínguez, Mercedes
dc.contributor.authorDomínguez Rodríguez, Lucas José
dc.date.accessioned2024-06-10T12:52:32Z
dc.date.available2024-06-10T12:52:32Z
dc.date.issued2024-05-31
dc.description.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.
dc.description.departmentDepto. de Sanidad Animal
dc.description.departmentDepto. de Producción Animal
dc.description.departmentDepto. de Medicina y Cirugía Animal
dc.description.facultyFac. de Veterinaria
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Ciencia e Innovación (España)
dc.description.statuspub
dc.identifier.citationSánchez-Morales, L., Porras, N., García-Seco, T. et al. Neuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2. Vet Res 55, 71 (2024). https://doi.org/10.1186/s13567-024-01325-7
dc.identifier.doi10.1186/s13567-024-01325-7
dc.identifier.essn1297-9716
dc.identifier.issn0928-4249
dc.identifier.officialurlhttps://doi.org/10.1186/s13567-024-01325-7
dc.identifier.urihttps://hdl.handle.net/20.500.14352/104800
dc.issue.number71
dc.journal.titleVeterinary Research
dc.language.isoeng
dc.page.final18
dc.page.initial1
dc.publisherSpringer
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-112966RB-I00/ES/VACUNAS BASADAS EN LA INMUNIDAD ENTRENADA ORIENTADA USANDO STREPTOCOCCUS SUIS COMO MODELO EXPERIMENTAL (TAIV-SUIS)/
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu636.09
dc.subject.keywordBCG stimulation
dc.subject.keywordSARS-CoV-2
dc.subject.keywordK18-hACE2
dc.subject.keywordNeuroinvasion
dc.subject.ucmVeterinaria
dc.subject.unesco3109 Ciencias Veterinarias
dc.titleNeuropathological lesions in intravenous BCG-stimulated K18-hACE2 mice challenged with SARS-CoV-2
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number55
dspace.entity.typePublication
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