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However, the molecular mechanisms underlying the interplay between these two viruses are still poorly understood. In this study, we utilized a comprehensive analysis of single\u2010cell transcriptomics to identify and characterize peripheral blood cell subsets in COVID\u201019 and HIV\u2010infected patients. Our findings revealed that COVID\u201019 and HIV exhibit a partially similar cellular composition and cell cycle distribution. Additionally, we identified a common pathogenesis in B\u2010cell subsets of COVID\u201019 and HIV patients, which showed abnormal activation states of the unfolded protein response (UPR) pathway. Based on B\u2010cell signature genes and UPR\u2010related genes, we developed a machine learning diagnostic model that can accurately diagnose both COVID\u201019 and HIV infections. Our model was validated using a large number of bulk transcriptome data sets and showed good clinical efficacy. Our study provides molecular insights into the single\u2010cell level interplay between SARS\u2010CoV\u20102 and HIV infections, suggesting a possible common disease mechanism that warrants further investigation.<\/jats:p>","DOI":"10.1002\/jmv.70538","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T11:53:57Z","timestamp":1754308437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Cell Omics Analysis Reveals Immunological Dysregulation in COVID\u201019 and HIV: Identifying a Shared Abnormality of B Cell Activation via the Unfolded Protein Response and Diagnostic Biomarkers Using Machine Learning Algorithms"],"prefix":"10.1002","volume":"97","author":[{"given":"Feng","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Nano\u2010carbon Modified Film Technology of Henan Province, Diagnostic Laboratory of Animal Diseases Xinxiang University Xinxiang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Nano\u2010carbon Modified Film Technology of Henan Province, Diagnostic Laboratory of Animal Diseases Xinxiang University Xinxiang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Nano\u2010carbon Modified Film Technology of Henan Province, Diagnostic Laboratory of Animal Diseases Xinxiang University Xinxiang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yandie","family":"Niu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Nano\u2010carbon Modified Film Technology of Henan Province, Diagnostic Laboratory of Animal Diseases Xinxiang University Xinxiang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Key Laboratory of Nano\u2010carbon Modified Film Technology of Henan Province, Diagnostic Laboratory of Animal Diseases Xinxiang University Xinxiang Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.12911"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2739-1"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30251-8"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001017"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0308-3"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60408"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01230-y"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6821a2"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14061401"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.37069"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","unstructured":"M. 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