{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:14:58Z","timestamp":1773288898756,"version":"3.50.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004480","name":"Natural Science Foundation of Shanxi Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004480","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Coronavirus disease 2019 (COVID-19) caused by coronavirus-2 (SARS-CoV-2) infection has rapidly spread throughout the world and become a major threat to human beings. Cytokine storm is a major cause of death in severe patients. Abatacept can suppress cytokines used as antirheumatic drugs in clinical applications. This study analyzed the molecular mechanisms of abatacept treatment for COVID-19. Differentially expressed genes (DEGs) were identified by analyzing expression profiling of abatacept treatment for rheumatoid arthritis (RA) patients and SARS-CoV-2 infection patients. We found that 59 DEGs were upregulated in COVID-19 patients and downregulated following abatacept treatment. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis showed that immune and inflammatory responses were potential regulatory mechanisms. Moreover, we verified 8 targeting genes and identified 15 potential drug candidates for the treatment of COVID-19. Our study illustrated that abatacept could be a promising property for preventing severe COVID-19, and we predicted alternative potential drugs for the treatment of SARS-CoV-2 infection.<\/jats:p>","DOI":"10.3389\/fmed.2022.951115","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T06:32:27Z","timestamp":1658730747000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Immunomodulatory mechanisms of abatacept: A therapeutic strategy for COVID-19"],"prefix":"10.3389","volume":"9","author":[{"given":"Dinglong","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hetong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiping","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjie","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunjiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"268","DOI":"10.34172\/aim.2020.09","article-title":"Epidemiology and clinical characteristics of COVID-19","volume":"23","author":"Huang","year":"2020","journal-title":"Arch Iran Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"173644","DOI":"10.1016\/j.ejphar.2020.173644","article-title":"Treatment for COVID-19: an overview","volume":"889","author":"Stasi","year":"2020","journal-title":"Eur J Pharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1111\/imm.13262","article-title":"T-cell responses and therapies against SARS-CoV-2 infection","volume":"162","author":"Toor","year":"2021","journal-title":"Immunology."},{"key":"B4","doi-asserted-by":"publisher","first-page":"827","DOI":"10.3389\/fimmu.2020.00827","article-title":"Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19)","volume":"11","author":"Diao","year":"2020","journal-title":"Front Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e20200678","DOI":"10.1084\/jem.20200678","article-title":"The many faces of the anti-COVID immune response","volume":"217","author":"Vardhana","year":"2020","journal-title":"J Exp Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1038\/s41418-020-0530-3","article-title":"COVID-19 infection: the perspectives on immune responses","volume":"27","author":"Shi","year":"2020","journal-title":"Cell Death Differ."},{"key":"B7","doi-asserted-by":"publisher","first-page":"105954","DOI":"10.1016\/j.ijantimicag.2020.105954","article-title":"Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality","volume":"55","author":"Zhang","year":"2020","journal-title":"Int J Antimicrob Agents."},{"key":"B8","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.ijid.2021.07.021","article-title":"Tocilizumab and systemic corticosteroids in the management of patients with COVID-19: a systematic review and meta-analysis","volume":"110","author":"Alkofide","year":"2021","journal-title":"Int J Infect Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1007\/s40265-017-0775-4","article-title":"Abatacept: a review in rheumatoid arthritis","volume":"77","author":"Blair","year":"2017","journal-title":"Drugs."},{"key":"B10","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1080\/1744666X.2019.1579642","article-title":"Abatacept for the treatment of rheumatoid arthritis","volume":"15","author":"Pombo-Suarez","year":"2019","journal-title":"Expert Rev Clin Immunol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/mr\/roab090","article-title":"Effectiveness and safety of subcutaneous abatacept in biologic-naive RA patients at week 52: a Japanese multicentre investigational study (ORIGAMI study)","author":"Tamura","year":"2021","journal-title":"Mod Rheumatol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.3390\/ph14121256","article-title":"Antirheumatic drugs against COVID-19 from the perspective of rheumatologists","volume":"14","author":"Kawazoe","year":"2021","journal-title":"Pharmaceuticals."},{"key":"B13","doi-asserted-by":"publisher","first-page":"11462","DOI":"10.1038\/s41598-021-90797-0","article-title":"Targeting of the CD80\/86 proinflammatory axis as a therapeutic strategy to prevent severe COVID-19","volume":"11","author":"Julia","year":"2021","journal-title":"Sci Rep."},{"key":"B14","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics."},{"key":"B17","doi-asserted-by":"publisher","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":"B18","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic acids research."},{"key":"B19","doi-asserted-by":"publisher","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":"Warde-Farley","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"Uhlen","year":"2015","journal-title":"Science."},{"key":"B21","doi-asserted-by":"publisher","first-page":"W234","DOI":"10.1093\/nar\/gkz240","article-title":"NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis.","volume":"47","author":"Zhou","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e90","DOI":"10.1002\/cpz1.90","article-title":"Gene set knowledge discovery with enrichr","volume":"1","author":"Xie","year":"2021","journal-title":"Curr Protoc."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1136\/gutjnl-2020-320926","article-title":"Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms","volume":"69","author":"Jin","year":"2020","journal-title":"Gut."},{"key":"B24","doi-asserted-by":"publisher","first-page":"519","DOI":"10.20892\/j.issn.2095-3941.2020.0289","article-title":"COVID-19 in cancer patients: risk, clinical features, and management","volume":"17","author":"Liu","year":"2020","journal-title":"Cancer Biol Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1093\/cid\/ciaa632","article-title":"Clinical features and outcomes of 105 hospitalized patients with COVID-19 in Seattle, Washington","volume":"71","author":"Buckner","year":"2020","journal-title":"Clin Infect Dis."},{"key":"B26","doi-asserted-by":"publisher","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 72314 cases from the Chinese center for disease control and prevention","volume":"323","author":"Wu","year":"2020","journal-title":"JAMA."},{"key":"B27","doi-asserted-by":"publisher","first-page":"11727","DOI":"10.1073\/pnas.2003138117","article-title":"Cell entry mechanisms of SARS-CoV-2","volume":"117","author":"Shang","year":"2020","journal-title":"Proc Natl Acad Sci USA."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2620","DOI":"10.1172\/JCI137244","article-title":"Clinical and immunological features of severe and moderate coronavirus disease 2019","volume":"130","author":"Chen","year":"2020","journal-title":"J Clin Investig."},{"key":"B29","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41579-020-00459-7","article-title":"Characteristics of SARS-CoV-2 and COVID-19","volume":"19","author":"Hu","year":"2021","journal-title":"Nat Rev Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e12998","DOI":"10.1111\/sji.12998","article-title":"Coronavirus disease 2019 (COVID-19): an overview of the immunopathology, serological diagnosis and management","volume":"93","author":"Anka","year":"2021","journal-title":"Scand J Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e12989","DOI":"10.1111\/sji.12989","article-title":"T cell immunobiology and cytokine storm of COVID-19","volume":"93","author":"Luo","year":"2021","journal-title":"Scand J Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"729559","DOI":"10.3389\/fpubh.2021.729559","article-title":"Efficacy of COVID-19 treatments: a bayesian network meta-analysis of randomized controlled trials","volume":"9","author":"Zhang","year":"2021","journal-title":"Front Public Health."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1007\/s10067-020-05190-5","article-title":"Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment","volume":"39","author":"Soy","year":"2020","journal-title":"Clin Rheumatol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.arbres.2020.06.007","article-title":"Biologic therapy in COVID-19","volume":"57","author":"Gonzalez-Gay","year":"2021","journal-title":"Arch Bronconeumol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"107612","DOI":"10.1016\/j.intimp.2021.107612","article-title":"A review on applications of abatacept in systemic rheumatic diseases","volume":"96","author":"Liu","year":"2021","journal-title":"Int Immunopharmacol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/S0140-6736(20)30211-7","article-title":"Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study","volume":"395","author":"Chen","year":"2020","journal-title":"Lancet."},{"key":"B37","doi-asserted-by":"publisher","first-page":"644055","DOI":"10.3389\/fendo.2021.644055","article-title":"Covid-19 and growth hormone\/insulin-like growth factor 1: study in critically and non-critically ill patients","volume":"12","author":"Ilias","year":"2021","journal-title":"Front Endocrinol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s10020-021-00412-1","article-title":"Syndecan-1, an indicator of endothelial glycocalyx degradation, predicts outcome of patients admitted to an ICU with COVID-19","volume":"27","author":"Zhang","year":"2021","journal-title":"Mol Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"bbab120","DOI":"10.1093\/bib\/bbab120","article-title":"Bioinformatics and machine learning approach identifies potential drug targets and pathways in COVID-19","volume":"22","author":"Auwul","year":"2021","journal-title":"Brief Bioinform."},{"key":"B40","doi-asserted-by":"publisher","first-page":"e14","DOI":"10.5808\/gi.20078","article-title":"A protein interactions map of multiple organ systems associated with COVID-19 disease","volume":"19","author":"Bharne","year":"2021","journal-title":"Genomics Inform."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1007\/s10528-021-10144-w","article-title":"Identification of key pathways and genes in SARS-CoV-2 infecting human intestines by bioinformatics analysis","volume":"60","author":"Chen","year":"2021","journal-title":"Biochem Genet."},{"key":"B42","doi-asserted-by":"publisher","first-page":"109826","DOI":"10.1016\/j.mehy.2020.109826","article-title":"Etoposide-based therapy for severe forms of COVID-19","volume":"142","author":"Hamizi","year":"2020","journal-title":"Med Hypotheses."},{"key":"B43","doi-asserted-by":"publisher","first-page":"7458","DOI":"10.3390\/molecules26247458","article-title":"Molecular docking and dynamics investigations for identifying potential inhibitors of the 3-chymotrypsin-like protease of SARS-CoV-2: repurposing of approved pyrimidonic pharmaceuticals for COVID-19 treatment","volume":"26","author":"Elzupir","year":"2021","journal-title":"Molecules."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e13","DOI":"10.1111\/jdv.16953","article-title":"Anti-androgens may protect against severe COVID-19 outcomes: results from a prospective cohort study of 77 hospitalized men","volume":"35","author":"Goren","year":"2021","journal-title":"J Eur Acad Dermatol Venereol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1007\/s12275-021-0617-7","article-title":"Raloxifene as a treatment option for viral infections","volume":"59","author":"Hong","year":"2021","journal-title":"J Microbiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e627","DOI":"10.1016\/S2665-9913(21)00212-5","article-title":"The effect of methotrexate and targeted immunosuppression on humoral and cellular immune responses to the COVID-19 vaccine BNT162b2: a cohort study","volume":"3","author":"Mahil","year":"2021","journal-title":"Lancet Rheumatol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"100110","DOI":"10.1016\/j.endmts.2021.100110","article-title":"COVID-19 and progesterone: Part 2. Unraveling High Severity, Immunity Patterns, Immunity grading, Progesterone and its potential clinical use","volume":"5","author":"Shah","year":"2021","journal-title":"Endocr Metab Sci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1016\/j.sjbs.2021.11.061","article-title":"Therapeutic potential of induced iron depletion using iron chelators in Covid-19","volume":"29","author":"Poonkuzhi Naseef","year":"2022","journal-title":"Saudi J Biol Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: consider cytokine storm syndromes and immunosuppression","volume":"395","author":"Mehta","year":"2020","journal-title":"Lancet."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1002\/med.21756","article-title":"SARS-CoV-2-mediated immune system activation and potential application in immunotherapy","volume":"41","author":"Tan","year":"2021","journal-title":"Med Res Rev."},{"key":"B52","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/s41577-020-0311-8","article-title":"The trinity of COVID-19: immunity, inflammation and intervention","volume":"20","author":"Tay","year":"2020","journal-title":"Nat Rev Immunol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1055\/a-1191-8094","article-title":"Inflammatory cell infiltration of adrenals in COVID-19","volume":"52","author":"Zinserling","year":"2020","journal-title":"Hormone Metab Res."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.951115\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T06:32:32Z","timestamp":1658730752000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.951115\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,25]]},"references-count":53,"alternative-id":["10.3389\/fmed.2022.951115"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.951115","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,25]]},"article-number":"951115"}}