{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:50:15Z","timestamp":1791827415230,"version":"4.3.4"},"reference-count":90,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010221","name":"Higher Education Commision, Pakistan","doi-asserted-by":"publisher","award":["Ref No. 2015891\/NRPU\/R&D\/HEC\/2021 2021)"],"award-info":[{"award-number":["Ref No. 2015891\/NRPU\/R&D\/HEC\/2021 2021)"]}],"id":[{"id":"10.13039\/501100010221","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The current study investigated host genetic associations with disease severity in COVID-19 patients of South Asian origin and explored its molecular basis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Covid-19 patients were stratified into disease severity groups based on the clinical and radiographic findings. Genomic DNA was extracted from peripheral blood samples. A two-step discovery and validation approach was utilized for genetic analysis. Whole-exome sequencing (WES) based variant prioritization was performed in a discovery cohort of severe disease patients followed by validation in an independent cohort. Bioinformatics analysis including data alignment, and annotation to the GRCh38 human reference genome was done by\n                      <jats:italic>Ensembl VEP<\/jats:italic>\n                      software. WES filtration pipeline utilizing predicted pathogenicity and population allele frequencies focused on the low-frequency and rare variants to filter out the variants of concern. Computational predictive tools and simulations were utilized for the structural and functional analysis of the identified high-risk SNP. Statistical analyses were done by SPSS version 24 and GraphPad Prism version 10.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The missense variant rs199726033 of\n                      <jats:italic>SVIL<\/jats:italic>\n                      gene demonstrated the highest recurrence in the WES discovery cohort. The minor allele frequency (29.2%) was substantially higher than that reported for South Asians in the\n                      <jats:italic>gnomAD<\/jats:italic>\n                      v4 database (1.051%). A significant association of the mutant AC genotype of rs199726033 and disease severity was found in the validation cohort. Protein modeling and structural analysis localized the variant within a functionally conserved Gelsolin domain. Moreover, functional and pathway analysis of the\n                      <jats:italic>SVIL<\/jats:italic>\n                      variant indicates its potential role in actin filament remodeling relevant to COVID-19 related vasculopathy and cytoskeleton dynamics thus influencing host-viral interactions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      A\n                      <jats:italic>SVIL<\/jats:italic>\n                      missense variant is associated with disease severity and may influence host cytoskeletal processes relevant to COVID-19 severity.\n                    <\/jats:p>\n                  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Pathology","volume":"17","author":"S Richards","year":"2015","journal-title":"Genet Med"},{"key":"pone.0360429.ref036"},{"issue":"23","key":"pone.0360429.ref037","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1158\/0008-5472.CAN-23-0816","article-title":"Analysis and visualization of longitudinal genomic and clinical data from the AACR Project GENIE Biopharma Collaborative in cBioPortal","volume":"83","author":"I de Bruijn","year":"2023","journal-title":"Cancer Res"},{"key":"pone.0360429.ref038"},{"key":"pone.0360429.ref039","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkae413","article-title":"ProtVar: mapping and contextualizing human missense variation","volume":"52","author":"JD Stephenson","year":"2024","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"pone.0360429.ref040","article-title":"UCSF ChimeraX: Tools for structure building and analysis","volume":"32","author":"EC Meng","year":"2023","journal-title":"Protein Science"},{"issue":"6664","key":"pone.0360429.ref041","doi-asserted-by":"crossref","DOI":"10.1126\/science.adg7492","article-title":"Accurate proteome-wide missense variant effect prediction with AlphaMissense","volume":"381","author":"J Cheng","year":"2023","journal-title":"Science"},{"key":"pone.0360429.ref042","article-title":"UniProt: The universal protein knowledgebase in 2023","volume":"51","year":"2023","journal-title":"Nucleic acids research"},{"key":"pone.0360429.ref043","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkae1082","article-title":"InterPro: the protein sequence classification resource in 2025","volume":"53","author":"M Blum","year":"2025","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pone.0360429.ref044","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/pro.3746","article-title":"VarSite: Disease variants and protein structure","volume":"29","author":"RA Laskowski","year":"2020","journal-title":"Protein 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Norris","year":"2021","journal-title":"Cells"},{"issue":"7","key":"pone.0360429.ref056","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.3390\/v14071586","article-title":"Manipulation of the host cytoskeleton by viruses: Insights and mechanisms","volume":"14","author":"D Seo","year":"2022","journal-title":"Viruses"},{"key":"pone.0360429.ref057","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41421-020-0147-1","article-title":"Comparative genetic analysis of the novel coronavirus (2019-nCoV\/SARS-CoV-2) receptor ACE2 in different populations","volume":"6","author":"Y Cao","year":"2020","journal-title":"Cell Discov"},{"issue":"6","key":"pone.0360429.ref058","doi-asserted-by":"crossref","DOI":"10.1016\/j.chom.2020.11.003","article-title":"Integrative imaging reveals SARS-CoV-2-induced reshaping of subcellular morphologies","volume":"28","author":"M Cortese","year":"2020","journal-title":"Cell Host 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Neuroinflammation"},{"key":"pone.0360429.ref071","doi-asserted-by":"crossref","first-page":"100088","DOI":"10.1016\/j.clinpr.2021.100088","article-title":"Recombinant human plasma gelsolin (rhu-pGSN) in a patient hospitalized with critical COVID-19 pneumonia","volume":"12","author":"JV Catteeuw","year":"2021","journal-title":"Clinical Infection in Practice"},{"issue":"6509","key":"pone.0360429.ref072","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.aaz1776","article-title":"The GTEx Consortium atlas of genetic regulatory effects across human tissues","volume":"369","author":"GTEx Consortium","year":"2020","journal-title":"Science"},{"key":"pone.0360429.ref073","doi-asserted-by":"crossref","first-page":"824851","DOI":"10.3389\/fcell.2022.824851","article-title":"COVID-19 and the vasculature: Current aspects and long-term consequences","volume":"10","author":"B Mart\u00ednez-Salazar","year":"2022","journal-title":"Front Cell Dev 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Li","year":"2025","journal-title":"Mol Ther"},{"issue":"4","key":"pone.0360429.ref081","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1111\/fcp.12994","article-title":"Targeting mevalonate pathway by zoledronate ameliorated pulmonary fibrosis in a rat model: Promising therapy against post-COVID-19 pulmonary fibrosis","volume":"38","author":"RH Mohamed","year":"2024","journal-title":"Fundam Clin Pharmacol"},{"issue":"4","key":"pone.0360429.ref082","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1093\/ehjcvp\/pvad025","article-title":"Vascular mechanisms of post-COVID-19 conditions: Rho-kinase is a novel target for therapy","volume":"9","author":"RA Sykes","year":"2023","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"issue":"4","key":"pone.0360429.ref083","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1007\/s11481-021-10029-0","article-title":"SARS-CoV-2 spike protein disrupts blood-brain barrier integrity via RhoA activation","volume":"16","author":"BJ DeOre","year":"2021","journal-title":"J Neuroimmune Pharmacol"},{"issue":"22","key":"pone.0360429.ref084","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1161\/CIRCULATIONAHA.112.091462","article-title":"Human genome-wide association and mouse knockout approaches identify platelet supervillin as an inhibitor of thrombus formation under shear stress","volume":"125","author":"LC Edelstein","year":"2012","journal-title":"Circulation"},{"issue":"1","key":"pone.0360429.ref085","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41587-022-01474-0","article-title":"A comprehensive SARS-CoV-2-human protein-protein interactome reveals COVID-19 pathobiology and potential host therapeutic targets","volume":"41","author":"Y Zhou","year":"2023","journal-title":"Nat Biotechnol"},{"issue":"1","key":"pone.0360429.ref086","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/s41587-022-01475-z","article-title":"A proteome-scale map of the SARS-CoV-2-human contactome","volume":"41","author":"D-K Kim","year":"2023","journal-title":"Nat Biotechnol"},{"key":"pone.0360429.ref087","doi-asserted-by":"crossref","first-page":"1775960","DOI":"10.3389\/fmed.2026.1775960","article-title":"A descriptive multilevel analysis associating COVID-19 with polymyositis: from genetic markers and candidate mediators to clinical hematological profiles","volume":"13","author":"M Chen","year":"2026","journal-title":"Front Med (Lausanne)"},{"issue":"13","key":"pone.0360429.ref088","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1084\/jem.20140455","article-title":"CCDC88B is a novel regulator of maturation and effector functions of T cells during pathological inflammation","volume":"211","author":"JM Kennedy","year":"2014","journal-title":"J Exp Med"},{"issue":"7","key":"pone.0360429.ref089","doi-asserted-by":"crossref","first-page":"3858","DOI":"10.4049\/jimmunol.1202999","article-title":"Induction of complement C3a 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