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The impacts of rheumatic disease and immunosuppression on the development of antibodies to SARS-CoV-2 are unknown. A study of healthcare workers showed that detectable SARS-CoV-2 antibodies were associated with reduced risk of SARS-CoV-2 reinfection, and the robustness of this neutralising antibody response has implications for seroprevalence studies and vaccine efficacy.1 While disease-modifying antirheumatic drugs (DMARDs) generally blunt the immune response to pathogens, immunosuppressive medications such as dexamethasone and baricitinib have efficacy in reducing the severity of COVID-19.2 3 Additionally, tumour necrosis factor inhibition has been proposed as a potential mechanism for enhancing germinal centre formation and antibody production in severe COVID-19.4 Understanding the SARS-CoV-2 antibody response after COVID-19 among rheumatic disease patients is therefore of particular interest.5
We examined the SARS-CoV-2 antibody response among patients with rheumatic diseases and past COVID-19 at the Mass General Brigham (MGB) health system in Boston, Massachusetts, USA. Patients with COVID-19 confirmed by positive PCR testing and rheumatic disease confirmed by electronic health record (EHR) review were identified as previously described.6 We extracted clinically obtained SARS-CoV-2 antibody results and other relevant variables from the EHR. This study was considered exempt by the MGB Institutional Review Board.
Out of 188 patients with PCR-confirmed COVID-19 and rheumatic disease, 13 patients had subsequent SARS-CoV-2 antibody testing (table 1). Of these, 2 had undetectable antibodies, 1 had variable results and 10 had positive antibodies. Of the two patients with negative antibodies, one patient had psoriatic arthritis treated with leflunomide and prednisone and had an uncomplicated COVID-19 course. The other patient had antineutrophil cytoplasmic antibody-associated vasculitis on rituximab, azathioprine and prednisone. This patient had negative SARS-CoV-2 antibodies between 28 and 216 days after COVID-19 and had a complicated course requiring intensive care unit admission. One patient with antiphospholipid syndrome on prednisone, cyclophosphamide, rituximab and eculizumab had initial positive antibodies 28 to 87 days after COVID-19. However, he had a negative antibody response by 107 days despite persistently positive PCR testing, phylogenetic analysis suggestive of persistent infection and viral evolution, and clinical concern for recurrent COVID-19, and he died from respiratory failure, as reported elsewhere.5
The remaining 10 patients had detectable SARS-CoV-2 antibodies despite the presence of rheumatic diseases and/or the use of immunosuppressive medications, including prednisone, methotrexate, azathioprine, etanercept, rituximab and belimumab. The median time between SARS-CoV-2 PCR and antibody testing was 91 days (IQR: 60–146 days). Of these 10 patients, 8 patients had full recovery, 1 patient had persistent fatigue, and 1 patient with systemic lupus erythematosus (without prior haematologic involvement) had a complicated course with recurrent episodes of thrombotic thrombocytopenic purpura.
This case series of rheumatic disease patients with PCR-confirmed COVID-19 and clinically obtained SARS-CoV-2 antibody testing indicates that the majority of patients (10, 77%) developed detectable SARS-CoV-2 antibodies, which is reassuring. Three patients had negative or variable SARS-CoV-2 antibodies, and two of these patients had severe COVID-19. Three patients were on rituximab; two patients on rituximab for many years had undetectable circulating CD19+ B cells and undetectable or variable SARS-CoV-2 antibodies, while one patient who had recently started rituximab (flow cytometry not available) had detectable SARS-CoV-2 antibodies. As tests were obtained as part of routine clinical care at a tertiary care centre, generalisability may be limited, antibody titers and tests for neutralising antibodies are not available, and the timing of antibody testing relative to SARS-CoV-2 infection is variable. Further studies are needed to investigate the effects of specific rheumatic diseases and DMARDs on the efficacy and durability of the antibody response to SARS-CoV-2.
JAS and ZSW are joint senior authors.
Handling editor Josef S Smolen
Contributors KMD’S, NS-B, TH, JAS and ZSW contributed to the conception and drafting of the article. All listed authors provided critical revision for important intellectual content and final approval.
Funding KMD and NSB are supported by the National Institutes of Health Ruth L. Kirschstein Institutional National Research Service Award [T32-AR-007258]. KMD is supported by the Rheumatology Research Foundation Scientist Development Award. JAS is funded by NIH/NIAMS (grant numbers K23 AR069688, R03 AR075886, L30 AR066953, P30 AR070253, and P30 AR072577), the Rheumatology Research Foundation R Bridge Award, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. ZSW is funded by NIH/NIAMS [K23AR073334 and L30 AR070520].
Competing interests JAS reports research support from Amgen and Bristol-Myers Squibb and consultancy fees from Bristol-Myers Squibb, Gilead, Inova, Janssen, Optum and Pfizer. ZSW reports research support from Bristol-Myers Squibb and Principia and consulting fees from Viela Bio and MedPace. All other authors report no competing interests.
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.
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