Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
An attenuated humoral response to SARS-CoV-2 vaccination has been observed in some patients with autoimmune disease,1 2 and immunosuppressed status has been associated with an increased risk of COVID-19 infection despite vaccination.3 Recent studies have demonstrated enhanced humoral response to third-dose SARS-CoV-2 vaccination in immunosuppressed transplant patients,4 5 but the immunogenicity of booster vaccination in other immunosuppressed populations is unknown. Thus, we sought to describe the humoral response in patients with autoimmune disease who received a booster SARS-CoV-2 vaccine.
Using our prospective cohort of patients with autoimmune disease,5 we included patients who reported receipt of a single booster dose of SARS-CoV-2 mRNA or adenovirus vector vaccine between 10 April and 11 June 2021. We observed serial anti-spike antibody responses among these participants.
A total of 18 participants received a booster SARS-CoV-2 vaccine dose (table 1). Most (13/18) were women with median (IQR) age of 55 (44–63) years. The most common autoimmune diagnoses included myositis (n=6) and inflammatory arthritis (n=3). Most (14/18) were on antimetabolite therapy; mycophenolate was the most commonly reported immunosuppressive therapy (n=8), with a median (IQR) daily dose of 3000 mg (2500–3000 mg). Participants completed initial vaccination with either Pfizer (n=8), Moderna (n=6) or Johnson & Johnson/Janssen (J&J) Ad26.COV2.S (n=4).
Anti-spike antibodies, evaluated via Roche Elecsys anti-RBD pan-Ig were negative in 10 participants (anti-RBD <0.8 U/mL) and low-positive (anti-RBD 0.8–500 U/mL) in six participants at a median of 29 (IQR 28–33) days after completion of initial vaccine series with median anti-spike antibody level (IQR) of <0.4 (<0.4–222 U/mL).
Participants underwent booster vaccine at a median of 77 (IQR 54–94) days after completion of initial series. Booster vaccines included single dose of Moderna (n=8), J&J (n=6) or Pfizer (n=4). Nine participants obtained a different vaccine platform (mRNA vs adenovirus) for the additional dose, while the remainder received the same vaccine type.
Repeat anti-spike antibody testing was performed at a median 30 (IQR 27–36) days after booster dose. Eighty-nine per cent of participants had an augmented humoral response following booster vaccination, with median anti-spike antibody level (IQR) of 2500 (885–2500 U/mL) (online supplemental figure 1). Among those negative following initial vaccine series, 80% were positive following the booster dose. All low-positive participants demonstrated high titre response following booster vaccination. Two patients remained negative following booster dose; neither adjusted peri-vaccination immunosuppression and reported taking anti-CD20 therapy and mycophenolate respectively. Most participants (10/15) continued immunosuppression during the initial vaccine series, compared with the minority (5/18) who continued therapy peri-booster.
In this first published series of booster-dose SARS-CoV-2 vaccination in patients with autoimmune disease, augmented antibody response was observed in the majority of participants. De novo antibody response was observed in eight participants, while an additional eight participants demonstrated increased antibody levels.
Our findings of enhanced humoral response to booster-dose SARS-CoV-2 vaccine are similar to those in immunosuppressed solid organ transplant recipients4 5; our participants demonstrated a more robust augmentation of humoral response, which may be reflective of baseline immune dysregulation in patients with autoimmune disease as well as the impact of peri-vaccination immunosuppressive management.
This study is limited by observational design, small and inhomogenous sample as well as absence of data on memory B-cell and T-cell response. The augmented effect of booster dose may be confounded by peri-booster pause of immunosuppression. Baseline disease activity or severity was not routinely collected.
Evidence-based approaches to safely optimising immune responses to SARS-CoV-2 vaccination for vulnerable populations are urgently required. While no antibody titre has been defined to correlate with protection, booster dosing may be an option for patients with limited antibody responses to standard vaccine series. The SARS-CoV-2 vaccination schedule may require further refinement in immunosuppressed populations. Further studies are needed to address safety and efficacy of booster vaccination, as well as optimal adjustment in peri-vaccination timing of immunosuppressive therapies; this should be investigated further in a clinical trial setting.
Patient and public involvement
Patients were not involved in the design, conduct or dissemination of the study, though this study was motivated by questions frequently posed by patients. The study has a public website (https://vaccineresponse.org/) and email account where we welcomed participants and the public to contact the research team. Results of the study will be shared with national RMD organisations for dissemination to their patient communities once published.
Patient consent for publication
This study was approved by the Johns Hopkins Institutional Review Board (IRB00248540). Participants gave informed consent to participate before taking part in this study.
Handling editor Josef S Smolen
Twitter @CaoilfhionnMD, @JenLAlejo
Contributors CMC, MT, SF, BJB, JLA, JA, LC-S, WAW, JG-W, DLS, JJP substantially contributed to the conception or design of the work; or the acquisition, analysis or interpretation of data for the work. CMC, MT, SF, BJB, JLA, JA, LC-S, WAW, JG-W, DLS, JJP contributed to drafting the work or revising it critically for important intellectual content. CMC, MT, SF, BJB, JLA, JA, LC-S, WAW, JG-W, DLS, JJP contributed to final approval of the version to be published. CMC, BJB, JLA, DLS, JJP contributed to 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.
Funding This work was supported by grant number F32DK124941 (Boyarsky), 5T32DK007713 (Alejo) and K23DK115908 (Garonzik‐Wang) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), K24AI144954 (Segev) from National Institute of Allergy and Infectious Diseases (NIAID), K23AR073927 (Paik) from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAIM).
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.
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.