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We integrated scRNA\u2010seq and spatial transcriptomics to profile immune cells and viral gene expression in COVID\u201019. Cell types and interactions were identified using Seurat\u2010based tools. Spatial transcriptomics analysis revealed viral hotspots, and GISAID data were used to track SARS\u2010CoV\u20102 mutations. Single\u2010cell and spatial transcriptomics analyses revealed that immune cells such as Neutrophils, Monocyte:CD14\u2009+\u2009, and T cell:CD4+ central memory are highly abundant in COVID\u201019 patients, particularly in mild and severe cases, and are concentrated in the central and upper regions of lung tissue. Pseudotime and CellChat analyses indicated that cell differentiation trajectories and communication networks shift toward heightened inflammatory responses in severe conditions. Spatial analysis of viral gene expression showed that SARS\u2010CoV\u20102 genes, especially Nucleoprotein, Spike and Envelope were highly expressed in central and upper\u2010right tissue regions, suggesting active viral replication. This localized viral activity was strongly associated with areas of immune cell infiltration and inflammation. The top 10 sustainable mutants in SARS\u2010CoV\u20102 genome with high frequency were observed in NSP12 (P323L, 99%, Switzerland), Spike (D614G, 97%, Switzerland), NSP4 (T492I, 79%, Switzerland), NSP6 (T77A, 70%, Guangdong), Orf9c (G50N, 64%, England), Nucleoprotein (D377Y, 62%, United States), Orf9b (T60A, 61%, France), NSP14 (I42V, 55%, United States), Envelope (T9I, 51.3%, Trinidad and Tobago), and NSP5 (P132H, 51.2%, United States). Following to this approach is crucial for a strong epidemiological reaction against the changing SARS\u2010CoV\u20102 outbreak.<\/jats:p>","DOI":"10.1002\/jmv.70586","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T09:59:52Z","timestamp":1757066392000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spatial Transcriptomics and Single Cell\u2010RNASeq Reveals Cellular Heterogeneity of SARS\u2010CoV\u20102 in Lung Tissues and Global Mutational Patterns in COVID\u201019 Patients"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7060-2619","authenticated-orcid":false,"given":"Seyed Taleb","family":"Hosseini","sequence":"first","affiliation":[{"name":"Medicinal Plants Research Center, Institute of Herbal Medicines and Metabolic Disorders Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3793-6553","authenticated-orcid":false,"given":"Mohammadamin","family":"Mahmanzar","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, John A. 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