Tehran University of Medical Sciences

Science Communicator Platform

Share By
Spatial Transcriptomics and Single Cell-Rnaseq Reveals Cellular Heterogeneity of Sars-Cov-2 in Lung Tissues and Global Mutational Patterns in Covid-19 Patients Publisher Pubmed



Hosseini ST ; Mahmanzar M ; Rahimian K ; Bayat S ; Gholamzad A ; Mollapoursisakht MM ; Farhadi A ; Kuehu DL ; Deng Y
Authors

Source: Journal of Medical Virology Published:2025


Abstract

RNA viruses have high mutation frequency, quick generation periods and vast population numbers, which promote fast evolution and host environment adaptation. We integrated scRNA-seq and spatial transcriptomics to profile immune cells and viral gene expression in COVID-19. Cell types and interactions were identified using Seurat-based tools. Spatial transcriptomics analysis revealed viral hotspots, and GISAID data were used to track SARS-CoV-2 mutations. Single-cell and spatial transcriptomics analyses revealed that immune cells such as Neutrophils, Monocyte:CD14 +, and T cell:CD4+ central memory are highly abundant in COVID-19 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-CoV-2 genes, especially Nucleoprotein, Spike and Envelope were highly expressed in central and upper-right 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-CoV-2 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-CoV-2 outbreak. © 2025 Elsevier B.V., All rights reserved.
Related Docs
View other Related Docs
1. Structure-Based Study of Immune Receptors As Eligible Binding Targets of Coronavirus Sars-Cov-2 Spike Protein, Journal of Molecular Graphics and Modelling (2021)
2. Deciphering Molecular Mechanisms of Sars-Cov-2 Pathogenesis and Drug Repurposing Through Grn Motifs: A Comprehensive Systems Biology Study, 3 Biotech (2023)
3. Covid-19: From the Molecular Mechanisms to Treatment, Tanaffos (2022)
Experts (# of related papers)
View all Related Experts
Nima Rezaei (4)
Abbas Rahimi Foroushani (1)
Other Related Docs
4. Targeted Therapy Strategies Against Sars-Cov-2 Cell Entry Mechanisms: A Systematic Review of in Vitro and in Vivo Studies, Journal of Cellular Physiology (2021)
5. A Novel Coronavirus Disease (Covid-19): A Review of Host Cell Signaling Pathways, Tanaffos (2020)
6. Cytokine Storm in the Pathophysiology of Covid-19: Possible Functional Disturbances of Mirnas, International Immunopharmacology (2021)
7. Dysregulation of the Immune Response in Coronavirus Disease 2019, Cell Biology International (2021)
8. Immunoediting in Sars-Cov-2: Mutual Relationship Between the Virus and the Host, International Immunopharmacology (2022)
9. The Importance of Genomic Changes of Sars-Cov-2 and Its Comparison With Iranian-Reported Covid-19 Sequencing; Whether Each Country Has to Design Its Treatment and Vaccine Production, Biomedical and Biotechnology Research Journal (2020)
10. Recent Findings on the Coronavirus Disease 2019 (Covid-19); Immunopathogenesis and Immunotherapeutics, International Immunopharmacology (2020)
11. Decoding Shared Molecular Mechanisms of Sars-Cov-2 and Hcov-Oc43 in Covid-19 Neurological Manifestations: A Systems Biology Approach, Gene Reports (2025)
12. Impact of Human Rhinoviruses on Gene Expression in Pediatric Patients With Severe Acute Respiratory Infection, Virus Research (2021)
13. Classification of Viral Proteins Expressed by the Sars-Cov-2 Genome, Acta Microbiologica Hellenica (2022)
14. Sars-Cov-2: Current Trends in Emerging Variants, Pathogenesis, Immune Responses, Potential Therapeutic, and Vaccine Development Strategies, International Immunopharmacology (2021)
15. Sars-Cov-2 Helicase Might Interfere With Cellular Nonsense-Mediated Rna Decay: Insights From a Bioinformatics Study, BMC Genomic Data (2023)
16. Novel and Emerging Mutations of Sars-Cov-2: Biomedical Implications, Biomedicine and Pharmacotherapy (2021)
17. Lymphopenia in Covid-19: Therapeutic Opportunities, Cell Biology International (2020)
18. Potential Antiviral Immune Response Against Covid-19: Lessons Learned From Sars-Cov, Advances in Experimental Medicine and Biology (2021)
19. Covid-19: A Trigger of Autoimmune Diseases, Cell Biology International (2023)
20. New Insights Into Extracellular and Intracellular Redox Status in Covid-19 Patients, Redox Biology (2023)