Rituximab-treated rheumatic patients: B cells predict seroconversion after COVID-19 boost or revaccination in initial vaccine non-responders
Abstract Objectives To investigate the effect of either a booster vaccine (one dose) or revaccination (two doses 3 weeks apart) on the antibody response to the COVID-19 mRNA vaccines in patients with rheumatic disease (RD) treated with rituximab (RTX) who had not produced vaccine-reactive antibodies...
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| Veröffentlicht in: | Rheumatology (Oxford, England) England), 2023-07, Vol.62 (7), p.2544-2549 |
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| creator | Ammitzbøll, Christian Kragh Thomsen, Marianne Bøgh Andersen, Jakob Jensen, Jens Magnus Berth From Hermansen, Marie-Louise Dahl Johannsen, Anders Larsen, Mads Lamm Mistegaard, Clara Elbæk Mikkelsen, Susan Szabados, Fruzsina Vils, Signe Risbøl Erikstrup, Christian Hauge, Ellen-Margrethe Troldborg, Anne |
| description | Abstract
Objectives
To investigate the effect of either a booster vaccine (one dose) or revaccination (two doses 3 weeks apart) on the antibody response to the COVID-19 mRNA vaccines in patients with rheumatic disease (RD) treated with rituximab (RTX) who had not produced vaccine-reactive antibodies after the initial two vaccine doses. Further, to examine if B cell levels in peripheral blood predicted seroconversion.
Methods
We included 91 RTX-treated RD patients previously vaccinated against COVID-19. Patients were offered revaccination or a single booster vaccination with an mRNA vaccine. Serum total antibodies against SARS-CoV-2 spike protein were measured before and 6 weeks after the last vaccine dose. B cells (CD19+CD45+) were measured by flow cytometry at inclusion.
Results
Of RD patients with undetectable SARS-CoV-2 antibody levels before inclusion, seroconversion was seen in 38% 6 weeks after the booster dose and 32% after revaccination. Patients receiving revaccination had significantly higher antibody levels than patients receiving a booster dose (P |
| doi_str_mv | 10.1093/rheumatology/keac666 |
| format | Article |
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Objectives
To investigate the effect of either a booster vaccine (one dose) or revaccination (two doses 3 weeks apart) on the antibody response to the COVID-19 mRNA vaccines in patients with rheumatic disease (RD) treated with rituximab (RTX) who had not produced vaccine-reactive antibodies after the initial two vaccine doses. Further, to examine if B cell levels in peripheral blood predicted seroconversion.
Methods
We included 91 RTX-treated RD patients previously vaccinated against COVID-19. Patients were offered revaccination or a single booster vaccination with an mRNA vaccine. Serum total antibodies against SARS-CoV-2 spike protein were measured before and 6 weeks after the last vaccine dose. B cells (CD19+CD45+) were measured by flow cytometry at inclusion.
Results
Of RD patients with undetectable SARS-CoV-2 antibody levels before inclusion, seroconversion was seen in 38% 6 weeks after the booster dose and 32% after revaccination. Patients receiving revaccination had significantly higher antibody levels than patients receiving a booster dose (P < 0.001). In both univariate and multivariate logistic regression analysis, only B cells higher than 10/µl before boost or revaccination were associated with seroconversion (P = 0.009 and P = 0.01, respectively). Seroconversion was independent of age, gender, diagnosis, cumulative RTX dose, RTX treatment time and time since last RTX treatment.
Conclusion
Continuously impaired humoral response to mRNA vaccines was found in most RTX-treated patients after a booster dose or revaccination. Seroconversion was observed in approximately one-third of the patients. Measurable B cells before boosting or revaccination was the strongest predictor of antibody response after boost or revaccination.
Graphical Abstract</description><identifier>ISSN: 1462-0324</identifier><identifier>EISSN: 1462-0332</identifier><identifier>DOI: 10.1093/rheumatology/keac666</identifier><identifier>PMID: 36445008</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Antibodies ; Antibodies, Viral ; Antibody response ; Blood levels ; CD19 antigen ; CD45 antigen ; COVID-19 ; COVID-19 - prevention & control ; COVID-19 vaccines ; Flow cytometry ; Humans ; Immune response (humoral) ; Immunization, Secondary ; Immunotherapy ; Lymphocytes B ; Monoclonal antibodies ; mRNA ; mRNA vaccines ; Peripheral blood ; Rituximab ; Rituximab - therapeutic use ; SARS-CoV-2 ; Seroconversion ; Severe acute respiratory syndrome coronavirus 2 ; Spike protein ; Vaccination ; Vaccines</subject><ispartof>Rheumatology (Oxford, England), 2023-07, Vol.62 (7), p.2544-2549</ispartof><rights>The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com 2022</rights><rights>The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.</rights><rights>The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-e7c4d3f57f5405642af4b2dddc2aa90fd1fb8d5cac5e20aa1711dce38b960d603</citedby><cites>FETCH-LOGICAL-c375t-e7c4d3f57f5405642af4b2dddc2aa90fd1fb8d5cac5e20aa1711dce38b960d603</cites><orcidid>0000-0002-9212-921X ; 0000-0002-9501-1268 ; 0000-0001-6551-6647</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36445008$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ammitzbøll, Christian</creatorcontrib><creatorcontrib>Kragh Thomsen, Marianne</creatorcontrib><creatorcontrib>Bøgh Andersen, Jakob</creatorcontrib><creatorcontrib>Jensen, Jens Magnus Berth</creatorcontrib><creatorcontrib>From Hermansen, Marie-Louise</creatorcontrib><creatorcontrib>Dahl Johannsen, Anders</creatorcontrib><creatorcontrib>Larsen, Mads Lamm</creatorcontrib><creatorcontrib>Mistegaard, Clara Elbæk</creatorcontrib><creatorcontrib>Mikkelsen, Susan</creatorcontrib><creatorcontrib>Szabados, Fruzsina</creatorcontrib><creatorcontrib>Vils, Signe Risbøl</creatorcontrib><creatorcontrib>Erikstrup, Christian</creatorcontrib><creatorcontrib>Hauge, Ellen-Margrethe</creatorcontrib><creatorcontrib>Troldborg, Anne</creatorcontrib><title>Rituximab-treated rheumatic patients: B cells predict seroconversion after COVID-19 boost or revaccination in initial vaccine non-responders</title><title>Rheumatology (Oxford, England)</title><addtitle>Rheumatology (Oxford)</addtitle><description>Abstract
Objectives
To investigate the effect of either a booster vaccine (one dose) or revaccination (two doses 3 weeks apart) on the antibody response to the COVID-19 mRNA vaccines in patients with rheumatic disease (RD) treated with rituximab (RTX) who had not produced vaccine-reactive antibodies after the initial two vaccine doses. Further, to examine if B cell levels in peripheral blood predicted seroconversion.
Methods
We included 91 RTX-treated RD patients previously vaccinated against COVID-19. Patients were offered revaccination or a single booster vaccination with an mRNA vaccine. Serum total antibodies against SARS-CoV-2 spike protein were measured before and 6 weeks after the last vaccine dose. B cells (CD19+CD45+) were measured by flow cytometry at inclusion.
Results
Of RD patients with undetectable SARS-CoV-2 antibody levels before inclusion, seroconversion was seen in 38% 6 weeks after the booster dose and 32% after revaccination. Patients receiving revaccination had significantly higher antibody levels than patients receiving a booster dose (P < 0.001). In both univariate and multivariate logistic regression analysis, only B cells higher than 10/µl before boost or revaccination were associated with seroconversion (P = 0.009 and P = 0.01, respectively). Seroconversion was independent of age, gender, diagnosis, cumulative RTX dose, RTX treatment time and time since last RTX treatment.
Conclusion
Continuously impaired humoral response to mRNA vaccines was found in most RTX-treated patients after a booster dose or revaccination. Seroconversion was observed in approximately one-third of the patients. Measurable B cells before boosting or revaccination was the strongest predictor of antibody response after boost or revaccination.
Graphical Abstract</description><subject>Antibodies</subject><subject>Antibodies, Viral</subject><subject>Antibody response</subject><subject>Blood levels</subject><subject>CD19 antigen</subject><subject>CD45 antigen</subject><subject>COVID-19</subject><subject>COVID-19 - prevention & control</subject><subject>COVID-19 vaccines</subject><subject>Flow cytometry</subject><subject>Humans</subject><subject>Immune response (humoral)</subject><subject>Immunization, Secondary</subject><subject>Immunotherapy</subject><subject>Lymphocytes B</subject><subject>Monoclonal antibodies</subject><subject>mRNA</subject><subject>mRNA vaccines</subject><subject>Peripheral blood</subject><subject>Rituximab</subject><subject>Rituximab - therapeutic use</subject><subject>SARS-CoV-2</subject><subject>Seroconversion</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Spike protein</subject><subject>Vaccination</subject><subject>Vaccines</subject><issn>1462-0324</issn><issn>1462-0332</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkV1rFDEUhoMotlb_gUjAG2_GPfmcGe_s-lUoFES9HTLJGU2dTcYkU-x_8EebZdciXgkhCeE5DznnJeQpg5cMerFJ33DdmRLn-PV28x2N1VrfI6dMat6AEPz-3Z3LE_Io52sAUEx0D8mJ0FIqgO6U_Proy_rT78zYlISmoKNHsbd0qTuGkl_Rc2pxnjNdEjpvC82Yoo3hBlP2MVAzFUx0e_Xl4k3DejrGmAuNiSa8Mdb6UD2V8vvlizczPTwjDTE0CfMSg6uqx-TBZOaMT47nGfn87u2n7Yfm8ur9xfb1ZWNFq0qDrZVOTKqdlASlJTeTHLlzznJjepgcm8bOKWusQg7GsJYxZ1F0Y6_BaRBn5MXBu6T4Y8Vchp3P-wZNwLjmgbeSa6W6llf0-T_odVxTqL8bBAMB0LNOV0oeKJtizgmnYUl1pul2YDDs0xr-Tms4plXLnh3l67hDd1f0J54KbA5AXJf_U_4GABipgA</recordid><startdate>20230705</startdate><enddate>20230705</enddate><creator>Ammitzbøll, Christian</creator><creator>Kragh Thomsen, Marianne</creator><creator>Bøgh Andersen, Jakob</creator><creator>Jensen, Jens Magnus Berth</creator><creator>From Hermansen, Marie-Louise</creator><creator>Dahl Johannsen, Anders</creator><creator>Larsen, Mads Lamm</creator><creator>Mistegaard, Clara Elbæk</creator><creator>Mikkelsen, Susan</creator><creator>Szabados, Fruzsina</creator><creator>Vils, Signe Risbøl</creator><creator>Erikstrup, Christian</creator><creator>Hauge, Ellen-Margrethe</creator><creator>Troldborg, Anne</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9212-921X</orcidid><orcidid>https://orcid.org/0000-0002-9501-1268</orcidid><orcidid>https://orcid.org/0000-0001-6551-6647</orcidid></search><sort><creationdate>20230705</creationdate><title>Rituximab-treated rheumatic patients: B cells predict seroconversion after COVID-19 boost or revaccination in initial vaccine non-responders</title><author>Ammitzbøll, Christian ; Kragh Thomsen, Marianne ; Bøgh Andersen, Jakob ; Jensen, Jens Magnus Berth ; From Hermansen, Marie-Louise ; Dahl Johannsen, Anders ; Larsen, Mads Lamm ; Mistegaard, Clara Elbæk ; Mikkelsen, Susan ; Szabados, Fruzsina ; Vils, Signe Risbøl ; Erikstrup, Christian ; Hauge, Ellen-Margrethe ; Troldborg, Anne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-e7c4d3f57f5405642af4b2dddc2aa90fd1fb8d5cac5e20aa1711dce38b960d603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antibodies</topic><topic>Antibodies, Viral</topic><topic>Antibody response</topic><topic>Blood levels</topic><topic>CD19 antigen</topic><topic>CD45 antigen</topic><topic>COVID-19</topic><topic>COVID-19 - prevention & control</topic><topic>COVID-19 vaccines</topic><topic>Flow cytometry</topic><topic>Humans</topic><topic>Immune response (humoral)</topic><topic>Immunization, Secondary</topic><topic>Immunotherapy</topic><topic>Lymphocytes B</topic><topic>Monoclonal antibodies</topic><topic>mRNA</topic><topic>mRNA vaccines</topic><topic>Peripheral blood</topic><topic>Rituximab</topic><topic>Rituximab - therapeutic use</topic><topic>SARS-CoV-2</topic><topic>Seroconversion</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Spike protein</topic><topic>Vaccination</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ammitzbøll, Christian</creatorcontrib><creatorcontrib>Kragh Thomsen, Marianne</creatorcontrib><creatorcontrib>Bøgh Andersen, Jakob</creatorcontrib><creatorcontrib>Jensen, Jens Magnus Berth</creatorcontrib><creatorcontrib>From Hermansen, Marie-Louise</creatorcontrib><creatorcontrib>Dahl Johannsen, Anders</creatorcontrib><creatorcontrib>Larsen, Mads Lamm</creatorcontrib><creatorcontrib>Mistegaard, Clara Elbæk</creatorcontrib><creatorcontrib>Mikkelsen, Susan</creatorcontrib><creatorcontrib>Szabados, Fruzsina</creatorcontrib><creatorcontrib>Vils, Signe Risbøl</creatorcontrib><creatorcontrib>Erikstrup, Christian</creatorcontrib><creatorcontrib>Hauge, Ellen-Margrethe</creatorcontrib><creatorcontrib>Troldborg, Anne</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Rheumatology (Oxford, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ammitzbøll, Christian</au><au>Kragh Thomsen, Marianne</au><au>Bøgh Andersen, Jakob</au><au>Jensen, Jens Magnus Berth</au><au>From Hermansen, Marie-Louise</au><au>Dahl Johannsen, Anders</au><au>Larsen, Mads Lamm</au><au>Mistegaard, Clara Elbæk</au><au>Mikkelsen, Susan</au><au>Szabados, Fruzsina</au><au>Vils, Signe Risbøl</au><au>Erikstrup, Christian</au><au>Hauge, Ellen-Margrethe</au><au>Troldborg, Anne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rituximab-treated rheumatic patients: B cells predict seroconversion after COVID-19 boost or revaccination in initial vaccine non-responders</atitle><jtitle>Rheumatology (Oxford, England)</jtitle><addtitle>Rheumatology (Oxford)</addtitle><date>2023-07-05</date><risdate>2023</risdate><volume>62</volume><issue>7</issue><spage>2544</spage><epage>2549</epage><pages>2544-2549</pages><issn>1462-0324</issn><eissn>1462-0332</eissn><abstract>Abstract
Objectives
To investigate the effect of either a booster vaccine (one dose) or revaccination (two doses 3 weeks apart) on the antibody response to the COVID-19 mRNA vaccines in patients with rheumatic disease (RD) treated with rituximab (RTX) who had not produced vaccine-reactive antibodies after the initial two vaccine doses. Further, to examine if B cell levels in peripheral blood predicted seroconversion.
Methods
We included 91 RTX-treated RD patients previously vaccinated against COVID-19. Patients were offered revaccination or a single booster vaccination with an mRNA vaccine. Serum total antibodies against SARS-CoV-2 spike protein were measured before and 6 weeks after the last vaccine dose. B cells (CD19+CD45+) were measured by flow cytometry at inclusion.
Results
Of RD patients with undetectable SARS-CoV-2 antibody levels before inclusion, seroconversion was seen in 38% 6 weeks after the booster dose and 32% after revaccination. Patients receiving revaccination had significantly higher antibody levels than patients receiving a booster dose (P < 0.001). In both univariate and multivariate logistic regression analysis, only B cells higher than 10/µl before boost or revaccination were associated with seroconversion (P = 0.009 and P = 0.01, respectively). Seroconversion was independent of age, gender, diagnosis, cumulative RTX dose, RTX treatment time and time since last RTX treatment.
Conclusion
Continuously impaired humoral response to mRNA vaccines was found in most RTX-treated patients after a booster dose or revaccination. Seroconversion was observed in approximately one-third of the patients. Measurable B cells before boosting or revaccination was the strongest predictor of antibody response after boost or revaccination.
Graphical Abstract</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>36445008</pmid><doi>10.1093/rheumatology/keac666</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-9212-921X</orcidid><orcidid>https://orcid.org/0000-0002-9501-1268</orcidid><orcidid>https://orcid.org/0000-0001-6551-6647</orcidid></addata></record> |
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| identifier | ISSN: 1462-0324 |
| ispartof | Rheumatology (Oxford, England), 2023-07, Vol.62 (7), p.2544-2549 |
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| language | eng |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection |
| subjects | Antibodies Antibodies, Viral Antibody response Blood levels CD19 antigen CD45 antigen COVID-19 COVID-19 - prevention & control COVID-19 vaccines Flow cytometry Humans Immune response (humoral) Immunization, Secondary Immunotherapy Lymphocytes B Monoclonal antibodies mRNA mRNA vaccines Peripheral blood Rituximab Rituximab - therapeutic use SARS-CoV-2 Seroconversion Severe acute respiratory syndrome coronavirus 2 Spike protein Vaccination Vaccines |
| title | Rituximab-treated rheumatic patients: B cells predict seroconversion after COVID-19 boost or revaccination in initial vaccine non-responders |
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