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Attenuated response to fourth dose SARS-CoV-2 vaccination in patients with autoimmune disease: a case series
  1. Mayan Teles1,
  2. Caoilfhionn M Connolly2,
  3. Sarah Frey3,
  4. Teresa Po-Yu Chiang3,
  5. Jennifer J Alejo3,
  6. Brian J Boyarsky1,
  7. Ami A Shah2,
  8. Jemima Albayda2,
  9. Lisa Christopher-Stine2,
  10. William A Werbel4,
  11. Dorry L Segev1,5,
  12. Julie J Paik2
  1. 1 Surgery, Johns Hopkins, Baltimore, Maryland, USA
  2. 2 Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  3. 3 Surgery, Johns Hopkins University, Baltimore, Maryland, USA
  4. 4 Infectious Diseases, Johns Hopkins University, Baltimore, Maryland, USA
  5. 5 Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
  1. Correspondence to Dr Dorry L Segev, Surgery, Johns Hopkins, Baltimore, MD 21205, USA; dorry{at}

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Severe, occasionally fatal breakthrough COVID-19 infections despite vaccination have been reported in patients with autoimmune disease,1 bringing vaccine efficacy in this population into question. Recently, the Food and Drug Administration authorised a third vaccine dose in immunocompromised patients who previously received two mRNA vaccines. We previously reported augmented antibody titers in 89% of patients with autoimmune disease after third SARS-CoV-2 vaccination dose2; herein, we describe antibody response in patients who received two additional SARS-CoV-2 vaccine doses after completion of initial series.

Patients with autoimmune diseases were recruited for our observational study as previously reported.3 We identified 18 patients ≥18 years of age who completed initial SARS-CoV-2 vaccine series (mRNA or adenovirus vector) and subsequently obtained two additional doses (AD) of SARS-CoV-2 vaccine between 30 April 2021 and 8 July 2021, six of whom were included in a previous report on response after three dose-vaccination.2 Participants with prior COVID-19 infection were excluded. Serial semiquantitative SARS-CoV-2 antibody testing was completed on the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay, which measures total antibody to the SARS-CoV-2 S-receptor binding domain protein (positive ≥0.8 U/mL) and a consistent correlate of plasma neutralising capacity.4 Participants provided informed consent electronically.

Thirteen participants were female, with a median (IQR) age of 56 (52–66) years (table 1). The most common autoimmune diagnoses included inflammatory arthritis (n=4), myositis (n=3) and overlap connective tissue …

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  • DLS and JJP are joint senior authors.

  • Handling editor Josef S Smolen

  • Twitter @CaoilfhionnMD, @JenLAlejo

  • MT and CMC contributed equally.

  • Contributors Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. MT, CMC, SF, BJB, JA, TP-YC, AAS, JA, LC-S, WAW, DLS and JJP. Drafting the work or revising it critically for important intellectual content. MT, CMC, SF, BJB, JA, TP-YC, AAS, JA, LC-S, WAW, DLS and JJP. Final approval of the version to be published MT, CMC, SF, BJB, JA, TP-YC, AAS, JA, LCS, WAW, DLS and JJP. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. CMC, MT, JA, DLS and JJP.

  • Funding This work was made possible by the generous support of the Ben Dov family. This work was supported by grant number F32DK124941 (Boyarsky), T32DK007713 (Alejo) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), K24AI144954 (Segev), U01AI138897 and K23AI157893 (Werbel) from National Institute of Allergy and Infectious Diseases (NIAID), K23AR073927 (Paik) from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

  • Disclaimer The analyses described here are the responsibility of the authors alone and do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organisations imply endorsement by the US Government.

  • Competing interests DLS has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallincrodt, Thermo Fisher Scientific. LC-S has the following financial disclosures: consultant fees from Janssen, Boehringer-Ingelheim, Mallinckrodt, EMD-Serono, Allogene and ArgenX. The other authors of this manuscript have no financial disclosures or completing interest to disclose as described by Annals of the Rheumatic Diseases.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

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