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Risk and prognosis of SARS-CoV-2 infection and vaccination against SARS-CoV-2 in rheumatic and musculoskeletal diseases: a systematic literature review to inform EULAR recommendations
  1. Féline P B Kroon1,2,
  2. Aurélie Najm3,
  3. Alessia Alunno4,
  4. Jan W Schoones5,
  5. Robert B M Landewé2,6,
  6. Pedro M Machado7,8,9,
  7. Victoria Navarro-Compán10
  1. 1 Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2 Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands
  3. 3 Institute of Infection, Immunity and Inflammation, University of Glasgow College of Medical Veterinary and Life Sciences, Glasgow, UK
  4. 4 Internal Medicine and Nephrology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
  5. 5 Directorate of Research Policy (formerly Walaeus Library), Leiden University Medical Center, Leiden, The Netherlands
  6. 6 Rheumatology & Clinical Immunology, Amsterdam University Medical Center, Amsterdam, The Netherlands
  7. 7 Department of Rheumatology, London North West University Healthcare NHS Trust, London, UK
  8. 8 Centre for Rheumatology & Department of Neuromuscular Diseases, University College London, London, UK
  9. 9 National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC), University College London Hospitals (UCLH) NHS Foundation Trust, London, UK
  10. 10 Rheumatology, University Hospital La Paz, Madrid, Spain
  1. Correspondence to Dr Féline P B Kroon, Rheumatology, Leiden University Medical Center, Leiden, Netherlands; fpbkroon{at}


Objectives Perform a systematic literature review (SLR) on risk and prognosis of SARS-CoV-2 infection and vaccination against SARS-CoV-2 in patients with rheumatic and musculoskeletal diseases (RMDs).

Methods Literature was searched up to 31 May 2021, including (randomised) controlled trials and observational studies with patients with RMD. Pending quality assessment, data extraction was performed and risk of bias (RoB) was assessed. Quality assessment required provision of (1) an appropriate COVID-19 case definition, and (2a) a base incidence (for incidence data) or (2b) a comparator, >10 cases with the outcome and risk estimates minimally adjusted for age, sex and comorbidities (for risk factor data).

Results Of 5165 records, 208 were included, of which 90 passed quality assessment and data were extracted for incidence (n=42), risk factor (n=42) or vaccination (n=14). Most studies had unclear/high RoB. Generally, patients with RMDs do not face more risk of contracting SARS-CoV-2 (n=26 studies) or worse prognosis of COVID-19 (n=14) than individuals without RMDs. No consistent differences in risk of developing (severe) COVID-19 were found between different RMDs (n=19). Disease activity is associated with worse COVID-19 prognosis (n=2), possibly explaining the increased risk seen for glucocorticoid use (n=13). Rituximab is associated with worse COVID-19 prognosis (n=7) and possibly Janus kinase inhibitors (n=3). Vaccination is generally immunogenic, though antibody responses are lower than in controls. Vaccine immunogenicity is negatively associated with older age, rituximab and mycophenolate.

Conclusion This SLR informed the July 2021 update of the European Alliance of Associations for Rheumatology recommendations for the management of RMDs in the context of SARS-CoV-2.

  • COVID-19
  • vaccination
  • antirheumatic agents
  • autoimmune diseases

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  • Handling editor Josef S Smolen

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  • Contributors All authors contributed to and finally approved the current manuscript. PMM and VN-C are joint last authors.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests RBML received honoraria for lecturing and consultation from AbbVie, Amgen, BMS, Celgene, Galapagos, Gilead, Janssen, Eli Lilly, Novartis, Pfizer and UCB and is the owner and director of Rheumatology Consultancy BV. PMM 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 National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the (UK) National Health Service, the NIHR or the (UK) Department of Health. VN-C received research grants/honoraria from AbbVie, Janssen, Lilly, Novartis, Pfizer and UCB.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.