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We evaluated the effects of SARS\u2010CoV\u20102 infection on human derived midbrain organoids by exposing them to the virus (multiplicity of infection 0.05, 16\u2010h exposure) and analyzing cellular and molecular changes at 4 and 28\u2009days post\u2010infection using immunofluorescence microscopy and RNA sequencing. SARS\u2010CoV\u20102 nucleocapsid protein preferentially colocalized with tyrosine hydroxylase\u2010positive (TH+) dopaminergic neurons, inducing neurite fragmentation and cellular stress. Transcriptomic analysis revealed dysregulation of pathways related to cell stress and death, DNA damage response, neurodevelopment, and neuronal survival at both timepoints. Persistent alterations in vesicle trafficking, Notch signaling, and mitochondrial function were observed at 28\u2009days post\u2010infection. Analysis of non\u2010coding RNA expression highlighted dysregulated genomic regions associated with viral replication and neurite growth. These findings demonstrate selective vulnerability of dopaminergic neurons to SARS\u2010CoV\u20102 infection with persistent molecular alterations, providing mechanistic insights into potential neurological consequences of COVID\u201019.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70486-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70486","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T07:15:37Z","timestamp":1779693337000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SARS\u2010CoV\u20102 Infection Induces Dopaminergic Neuronal Loss in Midbrain Organoids"],"prefix":"10.1111","volume":"170","author":[{"given":"Javier","family":"Jarazo","sequence":"first","affiliation":[{"name":"Developmental and Cellular Biology Luxembourg Centre for Systems Biomedicine University of Luxembourg  Esch\u2010sur\u2010Alzette Luxembourg"},{"name":"OrganoTherapeutics SARL  Esch\u2010sur\u2010Alzette Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveline Santos","family":"da Silva","sequence":"additional","affiliation":[{"name":"HIV Clinical and Translational Research Group, Department of Infection and Immunity Luxembourg Institute of Health  Esch\u2010sur\u2010Alzette Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3977-7469","authenticated-orcid":false,"given":"Enrico","family":"Glaab","sequence":"additional","affiliation":[{"name":"Biomedical Data Science Luxembourg Centre for Systems Biomedicine University of Luxembourg  Esch\u2010sur\u2010Alzette Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Perez\u2010Bercoff","sequence":"additional","affiliation":[{"name":"HIV Clinical and Translational Research Group, Department of Infection and Immunity Luxembourg Institute of Health  Esch\u2010sur\u2010Alzette Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-0559","authenticated-orcid":false,"given":"Jens C.","family":"Schwamborn","sequence":"additional","affiliation":[{"name":"Developmental and Cellular Biology Luxembourg Centre for Systems Biomedicine University of Luxembourg  Esch\u2010sur\u2010Alzette Luxembourg"},{"name":"OrganoTherapeutics SARL  Esch\u2010sur\u2010Alzette Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature20414"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3024"},{"key":"e_1_2_13_4_1","doi-asserted-by":"crossref","unstructured":"Ahlmann\u2010Eltze C. andI.Pati.2021.\u201cGgsignif: R Package for Displaying Significance Brackets for \u2018ggplot2\u2019.\u201dPsyArXiv.","DOI":"10.31234\/osf.io\/7awm6"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_2_13_6_1","first-page":"1941","article-title":"The Role of Rab Proteins in Parkinson's Disease Synaptopathy","volume":"10","author":"Bellucci A.","year":"2022","journal-title":"Biomedicine"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.026"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau3960"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84278-7"},{"key":"e_1_2_13_11_1","first-page":"665","article-title":"Infectability of Human BrainSphere Neurons Suggests Neurotropism of SARS\u2010CoV\u20102","volume":"37","author":"Bullen C. 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