{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T05:21:17Z","timestamp":1769318477372,"version":"3.49.0"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro","award":["E-26\/211.132\/2021"],"award-info":[{"award-number":["E-26\/211.132\/2021"]}]},{"name":"Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro","award":["E-26\/201.343\/2022"],"award-info":[{"award-number":["E-26\/201.343\/2022"]}]},{"DOI":"10.13039\/501100006507","name":"Oswaldo Cruz Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Oncocl\u00ednicas Institute"},{"DOI":"10.13039\/501100024786","name":"Oswaldo Cruz Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100024786","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cancer patients are highly vulnerable to severe COVID-19, requiring models that capture tumor\u2013virus interactions. We investigated tumor- and variant-specific effects of SARS-CoV-2 Gamma and Delta infections using patient-derived organoids (PDOs) from metastatic breast, lung, and colorectal cancers. Viral infection was quantified by Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) 24 h post-infection, and morphological changes and immune mediators were profiled. Genomic analysis using whole-exome sequencing was performed to identify contributing host-related gene alterations. The Delta variant produced consistently higher viral loads in lung and breast PDOs, while colorectal PDOs showed variable susceptibility. Infection led to reduced area and perimeter and increased circularity across all tumor types. Immune profiling revealed distinct responses: Gamma decreased Interferon alpha (IFN\u03b1) in lung PDOs and increased E-selectin in colorectal PDOs. Delta broadly reduced inflammatory mediators in lung [10 kDa interferon gamma-induced protein (IP-10) and Intercellular adhesion molecule 1 (ICAM-1)] and breast [Interleukin-6 (IL-6), Interleukin-13 (IL-13), and Interleukin-17A (IL-17A)] PDOs, while increasing Macrophage inflammatory protein 1-beta (MIP-1\u03b2) in colorectal PDOs. Host gene variants involved in trafficking (FYCO1 and RAB7A) and immune signaling (FOXA2, SFTPD, STAT3, and TET2) were associated with differential infection profiles. These findings show that SARS-CoV-2 induces variant- and tumor-specific morphological and immunological changes in cancer PDOs, highlighting the potential of this model to unravel host\u2013virus interactions and identify genetic factors that shape infection outcomes in cancer.<\/jats:p>","DOI":"10.3390\/ijms27031156","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T10:41:34Z","timestamp":1769164894000},"page":"1156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of Patient-Derived Tumor Organoids by SARS-CoV-2 Variants Across Cancer Types: A Study Combining Morphology, Inflammation, and Whole-Exome Profiling"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1325-0836","authenticated-orcid":false,"given":"Danielle","family":"Ferreira","sequence":"first","affiliation":[{"name":"Laboratory of Applied Genomics and Bioinovations, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil"},{"name":"Invitrocue Brasil, S\u00e3o Paulo 04513-020, SP, Brazil"},{"name":"Integrated Center for Translational Oncology Research (CIPOT), Center for Technological Development in Health, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tayanne","family":"Sassaro","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Genomics and Bioinovations, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anael Viana Pinto","family":"Alberto","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Genomics and Bioinovations, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3354-501X","authenticated-orcid":false,"given":"Mar\u00edlia","family":"de Melo","sequence":"additional","affiliation":[{"name":"Next Generation Sequencing Facility, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrien Alves","family":"Andrade","sequence":"additional","affiliation":[{"name":"Next Generation Sequencing Facility, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz Iandra","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Molecular Virology and Parasitology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil"},{"name":"Molecular Analysis Facility, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5340-8697","authenticated-orcid":false,"given":"Otac\u00edlio C.","family":"Moreira","sequence":"additional","affiliation":[{"name":"Molecular Virology and Parasitology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil"},{"name":"Molecular Analysis Facility, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9434-9582","authenticated-orcid":false,"given":"Daniel","family":"Moreira","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Genomics and Bioinovations, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil"},{"name":"Bioinformatics Core Facility, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7501-726X","authenticated-orcid":false,"given":"Thiago","family":"Parente","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Genomics and Bioinovations, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil"},{"name":"Bioinformatics Core Facility, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9406-2409","authenticated-orcid":false,"given":"Bruna","family":"Bordim","sequence":"additional","affiliation":[{"name":"Invitrocue Brasil, S\u00e3o Paulo 04513-020, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00falia","family":"de Abreu","sequence":"additional","affiliation":[{"name":"Invitrocue Brasil, S\u00e3o Paulo 04513-020, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiana","family":"Rond\u00e3o","sequence":"additional","affiliation":[{"name":"Integrated Center for Translational Oncology Research (CIPOT), Center for Technological Development in Health, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil"},{"name":"Oncoclinicas&Co.-Medica Scientia Innovation Research (MEDSIR), Sao Paulo 01304-001, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Canedo","sequence":"additional","affiliation":[{"name":"Integrated Center for Translational Oncology Research (CIPOT), Center for Technological Development in Health, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil"},{"name":"Oncoclinicas&Co.-Medica Scientia Innovation Research (MEDSIR), Sao Paulo 01304-001, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos Gil","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Integrated Center for Translational Oncology Research (CIPOT), Center for Technological Development in Health, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil"},{"name":"Oncoclinicas&Co.-Medica Scientia Innovation Research (MEDSIR), Sao Paulo 01304-001, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6512-6542","authenticated-orcid":false,"given":"Elen","family":"de Souza","sequence":"additional","affiliation":[{"name":"Molecular Virology and Parasitology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline","family":"Moreira","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Genomics and Bioinovations, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, RJ, Brazil"},{"name":"Next 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