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
Table 1.
Age, years | Sex | Rheumatic disease diagnosis | Rheumatic disease treatment | Timing of SARS-CoV-2 antibody test(s) relative to first positive COVID-19 PCR | SARS-CoV-2 antibody test result(s) | COVID-19 complications | COVID-19 pharmacologic treatment | COVID-19 clinical outcome |
---|---|---|---|---|---|---|---|---|
Negative/variable SARS-CoV-2 antibodies | ||||||||
48 | Female | Psoriatic arthritis | Leflunomide 10 mg daily, prednisone 10 mg daily | T+177 days | Negative total antibody* | None | None | Fully recovered |
62 | Female | ANCA-associated vasculitis | Rituximab 1 g (started T–6 years, most recent dose T–149 days), azathioprine 100 mg daily, prednisone 7.5 mg daily | T+28 days† T+71 days T+111 days T+216 days |
Negative IgG, negative IgM‡ Negative total antibody* Negative total antibody* Negative total antibody* |
Hospitalisation with ICU admission Respiratory failure requiring oxygen therapy by high flow nasal cannula |
Hydroxychloroquine, Remdesivir | Persistent cough (T+238 days). Oxygen requirement resolved by hospital discharge. |
45 | Male | Antiphospholipid syndrome | Prednisone 15 mg daily, cyclophosphamide 250 mg daily, rituximab 1 g (started T–5 years, most recent dose T–11 days), eculizumab 900 mg (started and most recent dose T-9 days) | T+28 days T+81 days T+87 days T+107 days |
Positive IgM, negative IgG‡ Positive IgM, positive IgG‡ Positive IgM, positive IgG‡ Negative total antibody* |
Hospitalisation with ICU admission Respiratory failure requiring mechanical ventilation; circulatory shock |
Remdesivir, SARS-CoV-2 antibody cocktail (regeneron) (T+145 days) | Death (T+154 days) |
Positive SARS-CoV-2 antibodies | ||||||||
26 | Female | Systemic lupus erythematosus | None | T+1 hour T+7 days |
Positive total antibody* Positive total antibody* |
Hospitalisation with ICU admission TTP requiring plasma exchange and glucocorticoids |
None | Recurrent TTP episode (T+58 days) |
71 | Female | Rheumatoid arthritis | None | T+58 days | Positive total antibody* | None | None | Fully recovered |
73 | Male | Psoriatic arthritis | Etanercept 50 mg weekly | T+60 days | Positive total antibody* | None | None | Fully recovered |
54 | Female | Systemic lupus erythematosus | Rituximab 720 mg (started T–86 days, most recent dose T–2 days) | T+60 days | IgG positive, IgM not performed‡ | None | None | Fully recovered |
63 | Female | Systemic lupus erythematosus | Azathioprine 100 mg daily, belimumab 720 mg monthly (started T–336 days, most recent dose T–20 days) | T+88 days | Positive total antibody* | None | None | Fully recovered |
55 | Female | Sarcoidosis | None | T+93 days | Positive total antibody* | None | None | Fully recovered |
52 | Female | Rheumatoid arthritis | None | T+94 days T+210 days |
Positive total antibody* Positive total antibody* |
Hospitalisation without ICU admission Supplemental oxygen by nasal cannula |
None | Fully recovered |
68 | Female | Polymyositis | Prednisone 6 mg daily, methotrexate 25 mg weekly | T+129 days | Positive total antibody* | None | None | Fully recovered |
51 | Female | Neurosarcoidosis | Methotrexate 15 mg weekly | T+155 days | Positive total antibody* | None | None | Fully recovered |
72 | Female | Psoriatic arthritis | Methotrexate 25 mg weekly | T+203 days | Positive total tntibody* | Hospitalisation without ICU admission; no oxygen requirement | None | Prolonged fatigue (T+262 days) |
Measured with the Roche Elecsys assay, which reports the positivity of total SARS-CoV-2 antibody (IgM and IgG) and has 99.5% sensitivity at 14 days after COVID-19 infection.
T=time zero, defined as the date of the first positive COVID-19 PCR test.
Measured with the Viracor Eurofins assay, which reports IgM and IgG antibody positivity to SARS-CoV-2. The sensitivity of the assay is unknown.
ANCA, antineutrophil cytoplasmic antibody; ICU, intensive care unit; PCR, polymerase chain reaction; T, time zero; TTP, thrombotic thrombocytopenic purpura.
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.
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.
Footnotes
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.
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