{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:30:15Z","timestamp":1787027415118,"version":"build-2736575974"},"reference-count":84,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006245","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["\u0110T\u0110LCN.102\/21"],"award-info":[{"award-number":["\u0110T\u0110LCN.102\/21"]}],"id":[{"id":"10.13039\/501100006245","id-type":"DOI","asserted-by":"publisher"}]},{"award":["\u0110T\u0110LCN.102\/21"],"award-info":[{"award-number":["\u0110T\u0110LCN.102\/21"]}],"id":[{"id":"https:\/\/ror.org\/02b207r52","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018055","name":"Hanoi Medical University","doi-asserted-by":"crossref","award":["1539\/Q\u0110-BKHCN"],"award-info":[{"award-number":["1539\/Q\u0110-BKHCN"]}],"id":[{"id":"10.13039\/100018055","id-type":"DOI","asserted-by":"crossref"}]},{"award":["1539\/Q\u0110-BKHCN"],"award-info":[{"award-number":["1539\/Q\u0110-BKHCN"]}],"id":[{"id":"https:\/\/ror.org\/01n2t3x97","id-type":"ROR","asserted-by":"publisher"}]},{"name":"authors\u2019 self-funded research group"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Host genetic variation contributes to the heterogeneous clinical outcomes of coronavirus disease 2019 (COVID-19), yet evidence from Southeast Asian populations remains limited. Methods: We investigated host genetic factors associated with COVID-19 severity in Vietnamese patients infected with the SARS-CoV-2 Delta variant using whole-exome sequencing. A total of 48 unvaccinated patients were enrolled. During sample-level quality control, one sample was excluded because the genetically inferred sex was discordant with the information recorded in the clinical medical record, leaving 47 samples (23 severe\/critical and 24 mild\/asymptomatic) for downstream genetic analyses. Gene-based association analysis was performed using MAGMA, followed by functional enrichment and interaction network analyses with Metascape and GeneMANIA. Results: Population structure analysis showed that the study participants clustered closely with the East Asian (EAS) reference population. No individual variant reached the prespecified multiple-testing-adjusted threshold, and no gene-level association survived Benjamini\u2013Hochberg correction. Using a nominal MAGMA gene-based p &lt; 0.01 threshold solely for exploratory prioritization, 44 genes were selected for downstream functional analyses. Functional enrichment highlighted RNA processing and mRNA maturation, together with mitochondrial, metabolic, immune-regulatory, and cellular homeostasis pathways. Network topology analysis further identified several highly connected genes, including CPSF4, MRPS34, ATP5MF, BUD31, SNRPD3, and HDAC1. Conclusions: These hypothesis-generating findings are consistent with a potentially polygenic contribution to severe COVID-19 and provide an exploratory systems-level framework for understanding host genetic susceptibility in the Vietnamese population, while identifying biologically plausible candidate genes and pathways for future validation.<\/jats:p>","DOI":"10.3390\/genes17080959","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:42:17Z","timestamp":1786974137000},"page":"959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Whole-Exome Sequencing Explores Host Genetic Susceptibility of COVID-19 Severity in Unvaccinated Vietnamese Patients Infected with the Delta Variant: A Hypothesis-Generating Study"],"prefix":"10.3390","volume":"17","author":[{"given":"Hoai Thu Thi","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Hanoi Medical University, Hanoi 100000, Vietnam"},{"name":"Faculty of Medical Laboratory Science, Danang University of Medical Technology and Pharmacy, Da Nang 550000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2776-4911","authenticated-orcid":false,"given":"Thanh-Van","family":"Ta","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Hanoi Medical University, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thuy Thi","family":"Le","sequence":"additional","affiliation":[{"name":"Faculty of Medical Laboratory Science, Danang University of Medical Technology and Pharmacy, Da Nang 550000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6254-3444","authenticated-orcid":false,"given":"Quyen-Diep","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Hanoi Medical University, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4783-6490","authenticated-orcid":false,"given":"Van","family":"Cao","sequence":"additional","affiliation":[{"name":"Faculty of Medical Laboratory Science, Danang University of Medical Technology and Pharmacy, Da Nang 550000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2000-043X","authenticated-orcid":false,"given":"Chan Dinh Khac","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Biomedical Research and Application Center, Phan Chau Trinh University, Da Nang 550000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9162-6795","authenticated-orcid":false,"given":"Tuan Nguyen","family":"Duc","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Hanoi Medical University, Hanoi 100000, Vietnam"},{"name":"Department of Clinical Laboratory, Hanoi Medical University Hospital, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc-Lan Thi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Hanoi Medical University, Hanoi 100000, Vietnam"},{"name":"Department of Clinical Laboratory, Hanoi Medical University Hospital, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1001\/jama.2020.2648","article-title":"Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention","volume":"323","author":"Wu","year":"2020","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41586-020-2521-4","article-title":"Factors associated with COVID-19-related death using OpenSAFELY","volume":"584","author":"Williamson","year":"2020","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1056\/NEJMoa2020283","article-title":"Genomewide Association Study of Severe Covid-19 with Respiratory Failure","volume":"383","author":"Ellinghaus","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/s41586-021-03767-x","article-title":"Mapping the human genetic architecture of COVID-19","volume":"600","author":"Initiative","year":"2021","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1038\/s41586-022-04826-7","article-title":"A first update on mapping the human genetic architecture of COVID-19","volume":"608","author":"Initiative","year":"2022","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41586-020-03065-y","article-title":"Genetic mechanisms of critical illness in COVID-19","volume":"591","author":"Clohisey","year":"2021","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41576-022-00478-5","article-title":"The human genetic epidemiology of COVID-19","volume":"23","author":"Niemi","year":"2022","journal-title":"Nat. Rev. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"eabd4570","DOI":"10.1126\/science.abd4570","article-title":"Inborn errors of type I IFN immunity in patients with life-threatening COVID-19","volume":"370","author":"Zhang","year":"2020","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"eabd4585","DOI":"10.1126\/science.abd4585","article-title":"Autoantibodies against type I IFNs in patients with life-threatening COVID-19","volume":"370","author":"Bastard","year":"2020","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1016\/j.ajhg.2021.05.017","article-title":"Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals","volume":"108","author":"Kosmicki","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41586-022-04576-6","article-title":"Whole-genome sequencing reveals host factors underlying critical COVID-19","volume":"607","author":"Kousathanas","year":"2022","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Nhung, V.P., Ton, N.D., Ngoc, T.T.B., Thuong, M.T.H., Hai, N.T.T., Oanh, K.T.P., Hien, L.T.T., Thach, P.N., Hai, N.V., and Ha, N.H. (2022). Host Genetic Risk Factors Associated with COVID-19 Susceptibility and Severity in Vietnamese. Genes, 13.","DOI":"10.3390\/genes13101884"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"de Leeuw, C.A., Mooij, J.M., Heskes, T., and Posthuma, D. (2015). MAGMA: Generalized gene-set analysis of GWAS data. PLoS Comput. Biol., 11.","DOI":"10.1371\/journal.pcbi.1004219"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"W214","DOI":"10.1093\/nar\/gkq537","article-title":"The GeneMANIA prediction server: Biological network integration for gene prioritization and predicting gene function","volume":"38","author":"Donaldson","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D325","DOI":"10.1093\/nar\/gkaa1113","article-title":"The Gene Ontology resource: Enriching a GOld mine","volume":"49","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"D587","DOI":"10.1093\/nar\/gkac963","article-title":"KEGG for taxonomy-based analysis of pathways and genomes","volume":"51","author":"Kanehisa","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_19","unstructured":"Illumina, Inc. (2025, December 22). Illumina DNA Prep with Exome 2.5 Enrichment Reference Guide. Available online: https:\/\/support-docs.illumina.com\/LP\/IlluminaDNAPrep-Exome\/Content\/LP\/Illumina_DNA\/Exome\/Protocol-Exome.htm."},{"key":"ref_20","unstructured":"Illumina, Inc. (2025, December 22). NextSeq 1000\/2000 Sequencing System. Available online: https:\/\/support.illumina.com\/sequencing\/sequencing_instruments\/nextseq-1000-2000\/documentation.htm."},{"key":"ref_21","unstructured":"Illumina, Inc. (2025, December 22). Illumina DRAGEN Bio-IT Platform User Guide. Version 2.6.5. Available online: https:\/\/support.illumina.com\/content\/dam\/illumina-support\/documents\/documentation\/software_documentation\/dragen-bio-it\/dragen-bio-it-platform-v2.6.5-user-guide-1000000085870-00.pdf."},{"key":"ref_22","unstructured":"Van der Auwera, G.A., and O\u2019Connor, B.D. (2020). Genomics in the Cloud, O\u2019Reilly Media."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: Rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"Gigascience"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/ng.3656","article-title":"Next-generation genotype imputation service and methods","volume":"48","author":"Das","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkad1025","article-title":"The Reactome Pathway Knowledgebase 2024","volume":"52","author":"Milacic","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.immuni.2015.12.006","article-title":"Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation","volume":"44","author":"Godec","year":"2016","journal-title":"Immunity"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"W60","DOI":"10.1093\/nar\/gky311","article-title":"GeneMANIA update 2018","volume":"46","author":"Franz","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E7","DOI":"10.1038\/s41586-023-06355-3","article-title":"A second update on mapping the human genetic architecture of COVID-19","volume":"621","author":"Initiative","year":"2023","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.cell.2017.05.038","article-title":"An Expanded View of Complex Traits: From Polygenic to Omnigenic","volume":"169","author":"Boyle","year":"2017","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nrg2918","article-title":"Network medicine: A network-based approach to human disease","volume":"12","author":"Barabasi","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1161\/CIRCRESAHA.111.258541","article-title":"The emerging paradigm of network medicine in the study of human disease","volume":"111","author":"Chan","year":"2012","journal-title":"Circ. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/j.cell.2020.10.004","article-title":"SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses","volume":"183","author":"Banerjee","year":"2020","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Mandilara, G., Koutsi, M.A., Agelopoulos, M., Sourvinos, G., Beloukas, A., and Rampias, T. (2021). The Role of Coronavirus RNA-Processing Enzymes in Innate Immune Evasion. Life, 11.","DOI":"10.3390\/life11060571"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mito.2020.06.008","article-title":"Mitochondria and microbiota dysfunction in COVID-19 pathogenesis","volume":"54","author":"Saleh","year":"2020","journal-title":"Mitochondrion"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.cmet.2020.07.007","article-title":"Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1alpha\/Glycolysis-Dependent Axis","volume":"32","author":"Codo","year":"2020","journal-title":"Cell Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.cell.2020.04.026","article-title":"Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19","volume":"181","author":"Liu","year":"2020","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.cell.2020.04.011","article-title":"The Architecture of SARS-CoV-2 Transcriptome","volume":"181","author":"Kim","year":"2020","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wang, C., Chen, L., Chen, Y., Jia, W., Cai, X., Liu, Y., Ji, F., Xiong, P., Liang, A., and Liu, R. (2022). Abnormal global alternative RNA splicing in COVID-19 patients. PLoS Genet., 18.","DOI":"10.1371\/journal.pgen.1010137"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7602","DOI":"10.1093\/nar\/gkad483","article-title":"Nsp14 of SARS-CoV-2 inhibits mRNA processing and nuclear export by targeting the nuclear cap-binding complex","volume":"51","author":"Katahira","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Dias, T.L., Mamede, I., de Toledo, N.E., Queiroz, L.R., Castro, I., Polidoro, R., Del-Bem, L.E., Nakaya, H., and Franco, G.R. (2024). SARS-CoV-2 Selectively Induces the Expression of Unproductive Splicing Isoforms of Interferon, Class I MHC, and Splicing Machinery Genes. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115671"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1146\/annurev-biochem-091719-064225","article-title":"RNA Splicing by the Spliceosome","volume":"89","author":"Wilkinson","year":"2020","journal-title":"Annu. Rev. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nrm.2017.86","article-title":"Mechanistic insights into precursor messenger RNA splicing by the spliceosome","volume":"18","author":"Shi","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e0256125","DOI":"10.1128\/spectrum.02561-25","article-title":"Epitranscriptomic signatures of m5C, m6A, and pseudouridine in COVID-19 reveal host RNA modifications involved in viral pathogenesis","volume":"14","author":"Mazdziarz","year":"2026","journal-title":"Microbiol. Spectr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/s41591-020-0944-y","article-title":"A single-cell atlas of the peripheral immune response in patients with severe COVID-19","volume":"26","author":"Wilk","year":"2020","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41577-020-00429-3","article-title":"The type I interferon response in COVID-19: Implications for treatment","volume":"20","author":"Lee","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/nri2975","article-title":"Mitochondria in innate immune responses","volume":"11","author":"West","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/ni.3704","article-title":"Mitochondria are the powerhouses of immunity","volume":"18","author":"Mills","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"54","DOI":"10.5694\/mja2.50674","article-title":"COVID-19 acute respiratory distress syndrome (ARDS): Clinical features and differences from typical pre-COVID-19 ARDS","volume":"213","author":"Gibson","year":"2020","journal-title":"Med. J. Aust."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nri.2016.70","article-title":"A guide to immunometabolism for immunologists","volume":"16","author":"Kishton","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Trinchese, G., Cimmino, F., Catapano, A., Cavaliere, G., and Mollica, M.P. (2024). Mitochondria: The gatekeepers between metabolism and immunity. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1334006"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1016\/j.cell.2015.11.045","article-title":"Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling","volume":"163","author":"York","year":"2015","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Dias, S.S.G., Soares, V.C., Ferreira, A.C., Sacramento, C.Q., Fintelman-Rodrigues, N., Temerozo, J.R., Teixeira, L., Nunes da Silva, M.A., Barreto, E., and Mattos, M. (2020). Lipid droplets fuel SARS-CoV-2 replication and production of inflammatory mediators. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1009127"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e202302049","DOI":"10.26508\/lsa.202302049","article-title":"Inhibition of the SREBP pathway prevents SARS-CoV-2 replication and inflammasome activation","volume":"6","author":"Soares","year":"2023","journal-title":"Life Sci. Alliance"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41421-020-0153-3","article-title":"Network-based drug repurposing for novel coronavirus 2019-nCoV\/SARS-CoV-2","volume":"6","author":"Zhou","year":"2020","journal-title":"Cell Discov."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13148-026-02094-0","article-title":"Genome-wide DNA methylation profiling in COVID-19 positive patients reveals alterations in pathways linked to neurological dysfunction","volume":"18","author":"Zameer","year":"2026","journal-title":"Clin. Epigenet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s13148-023-01515-8","article-title":"Comprehensive DNA methylation profiling of COVID-19 and hepatocellular carcinoma to identify common pathogenesis and potential therapeutic targets","volume":"15","author":"Luo","year":"2023","journal-title":"Clin. Epigenet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13148-021-01102-9","article-title":"Blood DNA methylation and COVID-19 outcomes","volume":"13","author":"Balnis","year":"2021","journal-title":"Clin. Epigenet."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Naik, N., Patel, M., and Sen, R. (2024). Developmental Impacts of Epigenetics and Metabolism in COVID-19. J. Dev. Biol., 12.","DOI":"10.3390\/jdb12010009"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Thaker, S.K., Ch\u2019ng, J., and Christofk, H.R. (2019). Viral hijacking of cellular metabolism. BMC Biol., 17.","DOI":"10.1186\/s12915-019-0678-9"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"107170","DOI":"10.1016\/j.phrs.2024.107170","article-title":"SARS-CoV-2 mitochondrial metabolic and epigenomic reprogramming in COVID-19","volume":"204","author":"Guarnieri","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.18632\/oncotarget.26669","article-title":"Pulsed SILAC-based proteomic analysis unveils hypoxia- and serum starvation-induced de novo protein synthesis with PHD finger protein 14 (PHF14) as a hypoxia sensitive epigenetic regulator in cell cycle progression","volume":"10","author":"Park","year":"2019","journal-title":"Oncotarget"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/s41597-020-00628-6","article-title":"Consensus transcriptional regulatory networks of coronavirus-infected human cells","volume":"7","author":"Ochsner","year":"2020","journal-title":"Sci. Data"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/s12276-021-00595-x","article-title":"From bedside to bench: Regulation of host factors in SARS-CoV-2 infection","volume":"53","author":"Ong","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"23928","DOI":"10.1038\/s41598-021-03309-5","article-title":"Identification of transcriptional regulatory network associated with response of host epithelial cells to SARS-CoV-2","volume":"11","author":"Su","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Esposito, S., D\u2019Abrosca, G., Antolak, A., Pedone, P.V., Isernia, C., and Malgieri, G. (2022). Host and Viral Zinc-Finger Proteins in COVID-19. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073711"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41579-022-00713-0","article-title":"SARS-CoV-2 pathogenesis","volume":"20","author":"Lamers","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/s41564-021-00958-0","article-title":"Cellular host factors for SARS-CoV-2 infection","volume":"6","author":"Baggen","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.tcb.2023.12.006","article-title":"Membrane remodeling and trafficking piloted by SARS-CoV-2","volume":"34","author":"Sergio","year":"2024","journal-title":"Trends Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e2200073","DOI":"10.1111\/boc.202200073","article-title":"A snapshot of protein trafficking in SARS-CoV-2 infection","volume":"115","author":"Prasad","year":"2023","journal-title":"Biol. Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e0002621","DOI":"10.1128\/mmbr.00026-21","article-title":"Molecular Virology of SARS-CoV-2 and Related Coronaviruses","volume":"86","author":"Kung","year":"2022","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s44298-024-00076-8","article-title":"A portrait of the infected cell: How SARS-CoV-2 infection reshapes cellular processes and pathways","volume":"2","author":"Marano","year":"2024","journal-title":"npj Viruses"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"100031","DOI":"10.1016\/j.cellin.2022.100031","article-title":"Endomembrane remodeling in SARS-CoV-2 infection","volume":"1","author":"Chen","year":"2022","journal-title":"Cell Insight"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/s41591-021-01329-2","article-title":"Single-cell multi-omics analysis of the immune response in COVID-19","volume":"27","author":"Stephenson","year":"2021","journal-title":"Nat. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cels.2020.10.003","article-title":"Large-Scale Multi-omic Analysis of COVID-19 Severity","volume":"12","author":"Overmyer","year":"2021","journal-title":"Cell Syst."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/s41586-020-2286-9","article-title":"A SARS-CoV-2 protein interaction map reveals targets for drug repurposing","volume":"583","author":"Gordon","year":"2020","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Khadzhieva, M.B., Kolobkov, D.S., Kashatnikova, D.A., Gracheva, A.S., Redkin, I.V., Kuzovlev, A.N., and Salnikova, L.E. (2023). Rare Variants in Primary Immunodeficiency Genes and Their Functional Partners in Severe COVID-19. Biomolecules, 13.","DOI":"10.3390\/biom13091380"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Turilli, E.S., Lualdi, M., and Fasano, M. (2022). Looking at COVID-19 from a Systems Biology Perspective. Biomolecules, 12.","DOI":"10.3390\/biom12020188"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.mayocpiqo.2020.09.008","article-title":"Redesigning COVID-19 Care With Network Medicine and Machine Learning","volume":"4","author":"Halamka","year":"2020","journal-title":"Mayo Clin. Proc. Innov. Qual. Outcomes"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.cell.2020.12.006","article-title":"Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks","volume":"184","author":"Schneider","year":"2021","journal-title":"Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.bsheal.2023.01.002","article-title":"Towards precision medicine: Omics approach for COVID-19","volume":"5","author":"Cen","year":"2023","journal-title":"Biosaf. Health"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1007\/s12325-022-02180-8","article-title":"Using Precision Medicine for the Diagnosis and Treatment of Viral Pneumonia","volume":"39","author":"Watkins","year":"2022","journal-title":"Adv. Ther."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/8\/959\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:13:28Z","timestamp":1787026408000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/8\/959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,15]]},"references-count":84,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["genes17080959"],"URL":"https:\/\/doi.org\/10.3390\/genes17080959","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,15]]}}}