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This study utilized K18-hACE2 transgenic mice to investigate the morphological, ultrastructural, and transcriptomic changes induced by SARS-CoV-2 infection in both lungs and brain tissues. Histopathological analysis at seven days post-infection revealed significant pulmonary damage characterized by interstitial pneumonia, alveolar septal thickening, with a marked inflammatory infiltrate predominantly consisting of neutrophils and lymphocytes, and an abnormal profile of type II pneumocytes. Concurrently, in the brain, we observed vasculitis, gliosis, and edema, indicating an inflammatory response and vascular compromise that can disturb the blood\u2013brain barrier. In addition, gene expression in lung tissue presented increased CCL2, IL10, and GDDA45D in infected mice and the downregulation of proinflammatory genes. However, in brain tissue, the increased expression of CCL2, CASP1, IL6, IFNB1, and GDDA45G inflammatory genes was observed in infected K18-hACE2 mice.<\/jats:p>","DOI":"10.3390\/microorganisms14040852","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T09:08:12Z","timestamp":1775812092000},"page":"852","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SARS-CoV-2 Effects on Respiratory and Neurological Systems: Morphological Findings and Gene Expression in K18-hACE2 Mice Model"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2189-7115","authenticated-orcid":false,"given":"Ana Luisa Teixeira","family":"de Almeida","sequence":"first","affiliation":[{"name":"Laboratory of Viral Morphology and Morphogenesis, Oswaldo Cruz Institute, Oswaldo Cruz Foundation\u2014Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4566-2545","authenticated-orcid":false,"given":"Andr\u00e9a Marques Vieira","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Immunological Technology, Department of Experimental and Preclinical Development, Bio-Manguinhos, Oswaldo Cruz Foundation\u2014Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8409-6350","authenticated-orcid":false,"given":"Mariana Mello e","family":"Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Trials, Department of Experimental and Preclinical Development, Bio-Manguinhos, Oswaldo Cruz Foundation\u2014Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5018-723X","authenticated-orcid":false,"given":"Miguel Pires Medeiros Diniz","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratory of Immunological Technology, Department of Experimental and Preclinical Development, Bio-Manguinhos, Oswaldo Cruz Foundation\u2014Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4533-1896","authenticated-orcid":false,"given":"Felipe Soares","family":"Coelho","sequence":"additional","affiliation":[{"name":"Laboratory of Immunological Technology, Department of Experimental and Preclinical Development, Bio-Manguinhos, Oswaldo Cruz Foundation\u2014Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1236-523X","authenticated-orcid":false,"given":"Lorenna Carvalho","family":"da Rosa","sequence":"additional","affiliation":[{"name":"Laboratory of Immunological Technology, Department of Experimental and Preclinical Development, Bio-Manguinhos, Oswaldo Cruz Foundation\u2014Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4047-2091","authenticated-orcid":false,"given":"Tamiris","family":"Azamor","sequence":"additional","affiliation":[{"name":"Laboratory of Immunological Technology, Department of Experimental and Preclinical Development, Bio-Manguinhos, Oswaldo Cruz Foundation\u2014Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3883-7714","authenticated-orcid":false,"given":"Carolina Baeta Salvador","family":"V\u00e1rady","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Trials, Department of Experimental and Preclinical Development, Bio-Manguinhos, Oswaldo Cruz Foundation\u2014Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5986-4642","authenticated-orcid":false,"given":"Bruno Jorge Duque","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Trials, Department of Experimental and Preclinical Development, Bio-Manguinhos, Oswaldo Cruz Foundation\u2014Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex Costa","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Trials, Department of Experimental and Preclinical Development, Bio-Manguinhos, Oswaldo Cruz Foundation\u2014Fiocruz, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata Tourinho","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Virological Technology, Department of Experimental and Preclinical Development, 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