{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T18:44:26Z","timestamp":1780598666598,"version":"3.54.1"},"reference-count":52,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"unspecified","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Socit Franaise de Rhmatologie","award":["COVIRIC study, ancillary from COVIDRIC study"],"award-info":[{"award-number":["COVIRIC study, ancillary from COVIDRIC study"]}]},{"name":"ANR RA-COVID","award":["Grant N 21 CO14 0011 02"],"award-info":[{"award-number":["Grant N 21 CO14 0011 02"]}]},{"name":"FRESENIUS KABI France"},{"name":"SANDOZ France"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,5,28]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) are at an increased risk for infection related to the use of immunomodulatory therapies (ITs). The objective of this study is to assess the impact of ITs on the adaptive immune responses to SARS-CoV-2.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>The study population comprised 94 patients (48 SpA; 46 RA; mean age of 5314 years) with a confirmed SARS-CoV-2 infection. 20 age-matched individuals (5017 years), corresponding to the patients household contacts infected at the same time, were included as the control population. Patients were stratified by treatment groups: methotrexate (MTX)\/sulfasalazine (n=17\/2), anti-TNF (n=24), anti-TNF+MTX (n=23), RTX (N=11), anti-IL17 (n=7) and others (n=11). The study compared the viral loads in plasma, stools and nasal swabs and the SARS-CoV-2-specific humoral and cellular immune responses (antibodies, B and T lymphocytes) following SARS-CoV-2 infection.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>\nViral persistence was not observed in the blood, nasopharynx and stools of patients undergoing ITs. Overall, the SARS-CoV-2-specific humoral and T-cell responses were preserved. Patients receiving RTX showed significantly lower IgA and IgG responses to SARS-CoV-2 compared with other treatment groups. Most patients, including RTX recipients, exhibited significant CD4+T cell responses. However, RTX therapy was associated with reduced SARS-CoV-2-specific activated CD8+T cells. A correlation was observed between humoral immune parameters and CD8\n<jats:sup>+<\/jats:sup>\nT cell activation.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>While most patients demonstrated the capacity to mount an immune response to SARS-CoV-2, treatment with RTX impacted both humoral and CD8+cell responses. Developing vaccines that elicit robust CD8+T cell responses could offer benefits to individuals undergoing ITs for inflammatory rheumatic diseases.<\/jats:p>\n<\/jats:sec>","DOI":"10.1136\/rmdopen-2025-005673","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T10:19:27Z","timestamp":1751969967000},"page":"e005673","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Adaptive immune responses to SARS-CoV-2 in DMARD-treated patients with chronic inflammatory rheumatisms"],"prefix":"10.1136","volume":"11","author":[{"given":"Maxime","family":"Beretta","sequence":"first","affiliation":[{"name":"Humoral Immunology Unit - INSERM U1222, Institut Pasteur and Universtity Paris Cit, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Martin","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, INSERM UMR 1163, Imagine Institute, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Fogel","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Hpital Cochin - Assistance Publique Hpitaux de Paris - Universit Paris Cit, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2309-5837","authenticated-orcid":false,"given":"Clementina","family":"Lpez-Medina","sequence":"additional","affiliation":[{"name":"Rheumatology, Reina Sofia University Hospital, Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Planchais","sequence":"additional","affiliation":[{"name":"Humoral Immunology Unit - INSERM U1222, Institut Pasteur and Universtity Paris Cit, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bruneau","sequence":"additional","affiliation":[{"name":"Service de Microbiologie (Unit de virologie), Hpital Europen Georges Pompidou, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Goncalves","sequence":"additional","affiliation":[{"name":"Inserm U1223, Innate Immunity Unit, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Avouac","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Hpital Cochin - Assistance Publique Hpitaux de Paris - Universit Paris Cit, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8252-7815","authenticated-orcid":false,"given":"Francis","family":"Berenbaum","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Pierre & Marie Curie Paris VI, Hopital Saint-Antoine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jrmie","family":"Sellam","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Pierre & Marie Curie Paris VI, Hopital Saint-Antoine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Fautrel","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Hpital Cochin - Assistance Publique Hpitaux de Paris - Universit Paris Cit, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7545-6385","authenticated-orcid":false,"given":"Jacques","family":"Morel","sequence":"additional","affiliation":[{"name":"Immunorhumatologie, CHU Lapeyronie, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Parfait","sequence":"additional","affiliation":[{"name":"Centre de Ressources Biologique - Hpital Cochin - Fdration des Centres de Ressources Biologiques-, Assistance Publique Hpitaux de Paris - Universit Paris Cit, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P","family":"Di Santo","sequence":"additional","affiliation":[{"name":"Inserm U1223, Innate Immunity Unit, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Behillil","sequence":"additional","affiliation":[{"name":"UMR 3569 CNRS, Molecular Genetics of RNA Viruses, National Reference Center Respiratory Viruses, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"van der Werf","sequence":"additional","affiliation":[{"name":"UMR 3569 CNRS, Molecular Genetics of RNA Viruses, National Reference Center Respiratory Viruses, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Pr","sequence":"additional","affiliation":[{"name":"Service de Microbiologie (Unit de virologie), Hpital Europen Georges Pompidou, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Latour","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, INSERM UMR 1163, Imagine Institute, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Mouquet","sequence":"additional","affiliation":[{"name":"Humoral Immunology Unit - INSERM U1222, Institut Pasteur and Universtity Paris Cit, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-3637","authenticated-orcid":false,"given":"Corinne","family":"Miceli-Richard","sequence":"additional","affiliation":[{"name":"Immunoregulation Unit, Institut Pasteur, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"key":"2025071409433438000_11.3.e005673.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2006.08.006"},{"key":"2025071409433438000_11.3.e005673.2","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1002\/acr.22831","article-title":"Global Prevalence of Spondyloarthritis: A Systematic Review and Meta-Regression Analysis","volume":"68","author":"Stolwijk","year":"2016","journal-title":"Arthritis Care & Research"},{"key":"2025071409433438000_11.3.e005673.3","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780370408"},{"key":"2025071409433438000_11.3.e005673.4","doi-asserted-by":"publisher","DOI":"10.1002\/art.10524"},{"key":"2025071409433438000_11.3.e005673.5","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/S0140-6736(14)61704-9","article-title":"Risk of serious infection in biological treatment of patients with rheumatoid arthritis: a systematic review and meta-analysis","volume":"386","author":"Singh","year":"2015","journal-title":"The Lancet"},{"key":"2025071409433438000_11.3.e005673.6","doi-asserted-by":"crossref","DOI":"10.1186\/1479-5876-12-77","article-title":"Infection risk in rheumatoid arthritis and spondyloarthropathy patients under treatment with DMARDs, corticosteroids and TNF-a antagonists","volume":"12","author":"Germano","year":"2014","journal-title":"J Transl Med"},{"key":"2025071409433438000_11.3.e005673.7","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel236"},{"key":"2025071409433438000_11.3.e005673.8","doi-asserted-by":"publisher","DOI":"10.1002\/art.21386"},{"key":"2025071409433438000_11.3.e005673.9","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.128637"},{"key":"2025071409433438000_11.3.e005673.10","doi-asserted-by":"publisher","DOI":"10.1002\/art.22504"},{"key":"2025071409433438000_11.3.e005673.11","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.083188"},{"key":"2025071409433438000_11.3.e005673.12","article-title":"Adverse effects of biologics: a network meta-analysis and Cochrane overview","volume":"2011","author":"Singh","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"2025071409433438000_11.3.e005673.13","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2019-001035","article-title":"Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases: a systematic literature review for the 2019 update of EULAR recommendations","volume":"5","author":"Rondaan","year":"2019","journal-title":"RMD Open"},{"key":"2025071409433438000_11.3.e005673.14","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1002\/art.42030","article-title":"SARS-CoV-2 Infection and COVID-19 Outcomes in Rheumatic Diseases: A Systematic Literature Review and Meta-Analysis","volume":"74","author":"Conway","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"2025071409433438000_11.3.e005673.15","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218946"},{"key":"2025071409433438000_11.3.e005673.16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2031364"},{"key":"2025071409433438000_11.3.e005673.17","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2021.03.027","article-title":"SARS-CoV-2 evolution in an immunocompromised host reveals shared neutralization escape mechanisms","volume":"184","author":"Clark","year":"2021","journal-title":"Cell"},{"key":"2025071409433438000_11.3.e005673.18","doi-asserted-by":"publisher","DOI":"10.1056\/nejmsb2104756"},{"key":"2025071409433438000_11.3.e005673.19","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-217871"},{"key":"2025071409433438000_11.3.e005673.20","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-eular.2252"},{"key":"2025071409433438000_11.3.e005673.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17488-8"},{"key":"2025071409433438000_11.3.e005673.22","doi-asserted-by":"publisher","DOI":"10.1126\/science.abg5268"},{"key":"2025071409433438000_11.3.e005673.23","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30196-1"},{"key":"2025071409433438000_11.3.e005673.24","doi-asserted-by":"crossref","DOI":"10.1126\/science.abf4063","article-title":"Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection","volume":"371","author":"Dan","year":"2021","journal-title":"Science"},{"key":"2025071409433438000_11.3.e005673.25","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2023-003094","article-title":"Impact of different classes of immune-modulating treatments on B cell-related and T cell-related immune response before and after COVID-19 booster vaccination in patients with immune-mediated diseases and primary immunodeficiency: a cohort study","volume":"9","author":"Koehm","year":"2023","journal-title":"RMD Open"},{"key":"2025071409433438000_11.3.e005673.26","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1093\/infdis\/jiad148","article-title":"Susceptibility to COVID-19 and Immunologic Response to Vaccination in Patients With Immune-Mediated Inflammatory Diseases","volume":"228","author":"Finckh","year":"2023","journal-title":"J Infect Dis"},{"key":"2025071409433438000_11.3.e005673.27","doi-asserted-by":"crossref","first-page":"101858","DOI":"10.1016\/j.trim.2023.101858","article-title":"The effects of methotrexate on the immune responses to the COVID-19 vaccines in the patients with immune-mediated inflammatory disease: A systematic review of clinical evidence","volume":"79","author":"Al-Haideri","year":"2023","journal-title":"Transpl Immunol"},{"key":"2025071409433438000_11.3.e005673.28","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2022-002417","article-title":"Immunogenicity and safety of a three-dose SARS-CoV-2 vaccination strategy in patients with immune-mediated inflammatory diseases on immunosuppressive therapy","volume":"8","author":"Syversen","year":"2022","journal-title":"RMD Open"},{"key":"2025071409433438000_11.3.e005673.29","doi-asserted-by":"crossref","DOI":"10.1186\/s12916-022-02587-8","article-title":"The persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses in patients on immunosuppressive therapy compared to healthy controls-a prospective cohort study","volume":"20","author":"Christensen","year":"2022","journal-title":"BMC Med"},{"key":"2025071409433438000_11.3.e005673.30","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaut.2022.102848","article-title":"Evaluation of humoral and cellular response to third dose of BNT162b2 mRNA COVID-19 vaccine in patients treated with B-cell depleting therapy","volume":"131","author":"Firinu","year":"2022","journal-title":"J Autoimmun"},{"key":"2025071409433438000_11.3.e005673.31","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1002\/art.42153","article-title":"Immunogenicity and Safety of Standard and Third-Dose SARS-CoV-2 Vaccination in Patients Receiving Immunosuppressive Therapy","volume":"74","author":"Syversen","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"2025071409433438000_11.3.e005673.32","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.159721","article-title":"Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune-mediated inflammatory diseases","volume":"7","author":"Dayam","year":"2022","journal-title":"JCI Insight"},{"key":"2025071409433438000_11.3.e005673.33","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ijid.2022.04.027","article-title":"Humoral and cellular responses to spike of d SARS-CoV-2 variant in vaccinated patients with immune-mediated inflammatory diseases","volume":"121","author":"Petrone","year":"2022","journal-title":"Int J Infect Dis"},{"key":"2025071409433438000_11.3.e005673.34","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1053\/j.gastro.2022.04.037","article-title":"Postacute COVID-19 is Characterized by Gut Viral Antigen Persistence in Inflammatory Bowel Diseases","volume":"163","author":"Zollner","year":"2022","journal-title":"Gastroenterology"},{"key":"2025071409433438000_11.3.e005673.35"},{"key":"2025071409433438000_11.3.e005673.36","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2021-002187","article-title":"SARS-CoV-2 breakthrough infections among vaccinated individuals with rheumatic disease: results from the COVID-19 Global Rheumatology Alliance provider registry","volume":"8","author":"Liew","year":"2022","journal-title":"RMD Open"},{"key":"2025071409433438000_11.3.e005673.37","doi-asserted-by":"crossref","first-page":"102744","DOI":"10.1016\/j.jaut.2021.102744","article-title":"Impaired immunogenicity to COVID-19 vaccines in autoimmune systemic diseases. High prevalence of non-response in different patients subgroups","volume":"125","author":"Ferri","year":"2021","journal-title":"J Autoimmun"},{"key":"2025071409433438000_11.3.e005673.38","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1007\/s10067-023-06638-0","article-title":"Impact of rituximab on humoral response to SARS-CoV-2 vaccination in previously vaccinated patients with autoimmune diseases","volume":"42","author":"Oliosi","year":"2023","journal-title":"Clin Rheumatol"},{"key":"2025071409433438000_11.3.e005673.39","doi-asserted-by":"crossref","DOI":"10.1136\/rmdopen-2021-001898","article-title":"Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases","volume":"8","author":"Sieiro Santos","year":"2022","journal-title":"RMD Open"},{"key":"2025071409433438000_11.3.e005673.40","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1125605","article-title":"Regulation of CD8 T cell by B-cells: A narrative review","volume":"14","author":"Van Meerhaeghe","year":"2023","journal-title":"Front Immunol"},{"key":"2025071409433438000_11.3.e005673.41","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/art.40766","article-title":"Dampening of CD8+ T Cell Response by B Cell Depletion Therapy in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis","volume":"71","author":"Nel","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"2025071409433438000_11.3.e005673.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2022.103740"},{"key":"2025071409433438000_11.3.e005673.43","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1007\/s00415-022-11350-1","article-title":"Ocrelizumab effect on humoral and cellular immunity in multiple sclerosis and its clinical correlates: a 3-year observational study","volume":"270","author":"Capasso","year":"2023","journal-title":"J Neurol"},{"key":"2025071409433438000_11.3.e005673.44","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-022-02871-1","article-title":"Incident and recurrent herpes zoster for first-line bDMARD and tsDMARD users in seropositive rheumatoid arthritis patients: a nationwide cohort study","volume":"24","author":"Jeong","year":"2022","journal-title":"Arthritis Res Ther"},{"key":"2025071409433438000_11.3.e005673.45","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220435"},{"key":"2025071409433438000_11.3.e005673.46","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636746"},{"key":"2025071409433438000_11.3.e005673.47","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636746"},{"key":"2025071409433438000_11.3.e005673.48","doi-asserted-by":"crossref","first-page":"e1037","DOI":"10.1093\/cid\/ciab954","article-title":"Robust T-Cell Responses in Anti-CD20-Treated Patients Following COVID-19 Vaccination: A Prospective Cohort Study","volume":"75","author":"Madelon","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2025071409433438000_11.3.e005673.49","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220435"},{"key":"2025071409433438000_11.3.e005673.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2015.04.010"},{"key":"2025071409433438000_11.3.e005673.51","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01028-7"},{"key":"2025071409433438000_11.3.e005673.52","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30200-0"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2025-005673","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T10:35:35Z","timestamp":1753180535000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2025-005673"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,7,5]]},"published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1136\/rmdopen-2025-005673"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2025-005673","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]}}}