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SARS-CoV-2 infection after vaccination in patients with inflammatory rheumatic and musculoskeletal diseases
  1. Saskia Lawson-Tovey1,2,
  2. Kimme L Hyrich2,3,
  3. Laure Gossec4,5,
  4. Anja Strangfeld6,
  5. Loreto Carmona7,
  6. Bernd Raffeiner8,
  7. Gözde Kübra Yardımcı9,
  8. Ludovic Trefond10,
  9. Nicolas Roux11,
  10. Ana Rodrigues12,13,
  11. Charalampos Papagoras14,
  12. Elsa F Mateus15,16,
  13. Xavier Mariette17,
  14. Pedro M Machado18,19,20
  1. 1 Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK
  2. 2 National Institute for Health Research Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester, UK
  3. 3 Centre for Epidemiology Versus Arthritis, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK
  4. 4 Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France
  5. 5 Rheumatology Department, Pitié-Salpêtrière Hospital, Sorbonne Université, AP-HP, Paris, France
  6. 6 German Rheumatism Research Center (DRFZ Berlin), Epidemiology Unit, Berlin, Germany
  7. 7 Instituto de Salud Musculoesquelética (INMUSC), Madrid, Spain
  8. 8 Department of Rheumatology, Central Hospital of Bolzano, Bolzano, Italy
  9. 9 Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
  10. 10 CHU Clermont Ferrand, Service de Médecine Interne, Hôpital Gabriel Montpied, Inserm U1071, INRA USC2018, M2iSH, Université Clermont Auvergne, Clermont-Ferrand, France
  11. 11 Service de Rhumatologie, Hôpital Robert Schuman, Metz, France
  12. 12, Sociedade Portuguesa de Reumatologia, Lisboa, Portugal
  13. 13 EpiDoC Unit, CEDOC, CHRC Campus Nova Medical School, Lisboa, Portugal
  14. 14 First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece
  15. 15 Portuguese League Against Rheumatic Diseases (LPCDR), Lisbon, Portugal
  16. 16 Standing Committee of People with Arthritis/Rheumatism in Europe (PARE), European League Against Rheumatism, Zurich, Switzerland
  17. 17 Department of Rheumatology, Université Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hopital Bicetre, Le Kremlin-Bicetre, France
  18. 18 Centre for Rheumatology & Department of Neuromuscular Diseases, University College London, London, UK
  19. 19 National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK
  20. 20 Department of Rheumatology, Northwick Park Hospital, London North West University Healthcare NHS Trust, London, UK
  1. Correspondence to Dr Pedro M Machado, Centre for Rheumatology & Department of Neuromuscular Diseases, University College London, London WC1E 6BT, UK; p.machado{at}

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Patients with inflammatory rheumatic and musculoskeletal diseases (iRMDs) are often treated with immunomodulatory or immunosuppressive medications; consequently, they have been excluded alongside other immunocompromised patients from late stages of SARS-CoV-2 vaccine trials. SARS-CoV-2 vaccine efficacy in this population is unclear, though initial data are reassuring overall.

However, a slightly lower SARS-CoV-2 immunogenicity of vaccines has been documented in some patients with iRMD.1 2 Some common rheumatic and musculoskeletal disease (RMD) medications have been highlighted as possible influential factors on immunogenicity, particularly rituximab (RTX), mycophenolate mofetil (MMF), methotrexate (MTX), abatacept and glucocorticoids.3–7

The European Alliance of Associations for Rheumatology (EULAR) launched a COVID-19 registry in March 2020, capturing COVID-19 outcomes in the European RMD population. Questions on reinfection and vaccination were added in January 2021. A further EULAR registry (COVAX) was launched in February 2021 to collect data on COVID-19 vaccination and related adverse events among patients with RMD. Here we describe a series of patients who contracted SARS-CoV-2 infection after COVID-19 vaccination between 19 January 2021 and 27 July 2021.

The series consists of 38 adults with iRMDs, 8 from the COVID-19 registry (<1%, out of 9118 patients with iRMD diagnosed with COVID-19) and 30 from the COVAX registry (<1%, out of 4393). Cases were deemed eligible if they were ‘partially vaccinated’ (≥14 days after dose 1 to <14 days after dose 2) or ‘fully vaccinated’ (≥14 days after dose 2/single dose), as per Centers for Disease Control and Prevention definitions8 (17 cases were excluded for this reason). A quarter (26%) were fully vaccinated and 28 cases (74%) were partially vaccinated.

As shown in table 1, 76% of the series is female, with a median age of 58 (IQR 49–65) from 12 countries. The most frequent iRMD diagnoses were rheumatoid arthritis (RA, 45%), axial spondyloarthritis (axSpA, 24%), systemic sclerosis (SSc, 8%) and systemic lupus erythematosus (8%). Most were in remission (47%) or had low disease activity (34%). The top iRMD medications were glucocorticoids (32%), MTX (26%) and tumour necrosis factor inhibitors (TNFi, 26%). The median glucocorticoid dose in users was 5 mg/day (IQR 5–10).

Table 1

Summary of 38 cases of SARS-CoV-2 infection ≥14 days after the first/single SARS-CoV-2 vaccine dose in the European Alliance of Associations for Rheumatology COVID-19 and COVAX registries, and breakdown by vaccination status

The most common comorbidities among COVID-19 registry cases were hypertension (38%) and cardiovascular disease (25%). Comorbidities are not reported in the COVAX registry. Out of the 30 COVAX cases, 29 had no SARS-CoV-2 infection prior to vaccination, and this was unknown in one case. These data are not collected in the COVID-19 registry.

Seventy-nine per cent received the Pfizer/BioNTech vaccine; 11% received AstraZeneca; 8% received CoronaVac/Sinovac; and 3% received Moderna. Sixty-one per cent had one vaccine dose before COVID-19; 34% had two; and 5% had three. Median times from vaccination to infection are shown in table 1.

Table 2

Summary of 34 cases of SARS-CoV-2 infection ≥14 days after the first/single SARS-CoV-2 vaccine dose in the European Alliance of Associations for Rheumatology COVID-19 and COVAX registries, stratified by COVID-19 outcome (excluding cases with missing/unknown COVID-19 outcome, N=4)

Most patients (74%) fully recovered from the SARS-CoV-2 infection; however, several patients recovered with ongoing sequelae (8%) and three patients died (8%).

Two of the deceased patients were male: one >80-year-old man with SSc, treated with glucocorticoids (10 mg/day) and MMF, who received one Pfizer vaccine 18 days prior to SARS-CoV-2 infection (therefore this patient was not fully vaccinated); one >70-year-old man with RA, treated with glucocorticoids (5 mg/day) who received two Pfizer doses (44 and 22 days before SARS-CoV-2 infection). The other patient was female: a >70-year-old woman with RA and Sjogren’s syndrome, treated with RTX (the most recent RTX infusion was 195 days before the first vaccine), who received two Pfizer vaccines (60 and 32 days prior to infection) (table 2).

The three patients who recovered with ongoing sequelae had axSpA and RA, and were treated with abatacept, interleukin-6 inhibitors, sulfasalazine and TNFi (table 2).

Overall, the low numbers of SARS-CoV-2 infection postvaccination in both registries are encouraging. Some observations described here have already been highlighted in existing research; for example, all three deceased patients were treated with medications that are potential negative influences on postvaccination SARS-CoV-2 immunogenicity in the RMD population.3 7 However, no vaccine has perfect efficacy; thus, a small number of postvaccination diagnoses of SARS-CoV-2 infections were expected, similarly to existing clinical trial observations; the influence of RMD medications on immunity after vaccination is still unclear.

There are significant limitations to this case series. The sample size is not sufficiently powered to evaluate associations between iRMD population-specific factors and SARS-CoV-2 infection after COVID-19 vaccination or to calculate a vaccine failure rate. Both the EULAR COVID-19 and COVAX registries rely on voluntary case submission, leading to selection bias in the data. No information is provided concerning the presence or the titre of postvaccine antibodies at the time of the infection. No causal conclusions can be drawn from this dataset, and the observations highlighted here cannot be extrapolated onto the wider iRMD population. Further research is needed to more deeply examine possible links between iRMD and medication-specific factors and SARS-CoV-2 infection after vaccination.

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Patient consent for publication


We thank all rheumatology providers who entered data into the registries. Study data were collected and managed using Research Electronic Data Capture (REDCap) electronic data capture tools hosted at The University of Manchester. REDCap is a secure, web-based software platform designed to support data capture for research studies, providing (1) an intuitive interface for validated data capture, (2) audit trails for tracking data manipulation and export procedures, (3) automated export procedures for seamless data downloads to common statistical packages, and (4) procedures for data integration and interoperability with external sources.



  • Handling editor Josef S Smolen

  • Twitter @saskiaamber, @carmona_loreto, @pedrommcmachado

  • Contributors SL-T analysed the data. SL-T and PMM drafted the first version of the manuscript. All authors revised the manuscript and approved the final version.

  • Funding Financial support from the European Alliance of Associations for Rheumatology.

  • Disclaimer The views expressed here are those of the authors and do not necessarily represent the views of the European League Against Rheumatism, the UK National Health Service or the UK Department of Health, or any other organisation.

  • Competing interests KLH reports she has received non-personal speaker’s fees from Abbvie and grant income from BMS, UCB, and Pfizer, all unrelated to this manuscript; KLH is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre. LG reports personal consultant fees from AbbVie, Amgen, BMS, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis and UCB, and grants from Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi and Galapagos, all unrelated to this manuscript. AS reports research grants from a consortium of 14 companies (among them AbbVie, BMS, Celltrion, Fresenius Kabi, Gilead/Galapagos, Lilly, Mylan/Viatris, Hexal, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis and UCB) supporting the German RABBIT register and personal fees from lectures for AbbVie, Celltrion, MSD, Roche, BMS and Pfizer, all outside the submitted work. LC has not received fees or personal grants from any laboratory, but her institute works by contract for laboratories among other institutions, such as Abbvie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, S.A., Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal GmbH and UCB Pharma. AR reports research grants and consultant fees from Amgen and Pfizer, all unrelated to this manuscript. CP has received research grants from Pharmaserve-Lilly, Faran and Demo, and speaking and consultant fees from Abbvie, Novartis, Genesis, Aenosasis, GSK and Pfizer, all unrelated to this manuscript. EFM reports that LPCDR received support for specific activities: grants from Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern and GAfPA; grants and non-financial support from Pfizer; non-financial support from Grünenthal GmbH, outside the submitted work. XM reports personal consultant fees from BMS, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis and UCB, and grants from Ose Pharmaceutical and Pfizer, all unrelated to this manuscript. PMM has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche and UCB, all unrelated to this manuscript, and is supported by the NIHR University College London Hospitals Biomedical Research Centre.

  • Patient and public involvement Patients and/or the public were involved in the design, conduct, reporting or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.