key: cord-0705134-rwn35k34 authors: Baker, Matthew C.; Mallajosyula, Vamsee; Davis, Mark M.; Boyd, Scott D.; Nadeau, Kari C.; Robinson, William H. title: Effective Viral Vector SARS‐CoV‐2 Booster Vaccination in a Patient with Rheumatoid Arthritis after Initial Ineffective mRNA Vaccine Response date: 2021-09-12 journal: Arthritis Rheumatol DOI: 10.1002/art.41978 sha: 15308f217f7333b3ea77d8876ca3c76fafba7cb4 doc_id: 705134 cord_uid: rwn35k34 Managing patients with rheumatic disease during the COVID‐19 pandemic has posed a unique challenge. Immunosuppressed patients are at an increased risk for developing severe COVID‐19 and may not derive full protection from the vaccine (1‐5). Thus, it is paramount we develop strategies whereby rheumatic disease patients can be protected from the pandemic virus and its variants. This article is protected by copyright. All rights reserved Word Count: 542 Funding Sources: None Article Type: Letter to the Editor Managing patients with rheumatic disease during the COVID-19 pandemic has posed a unique challenge. Immunosuppressed patients are at an increased risk for developing severe COVID-19 and may not derive full protection from the vaccine (1) (2) (3) (4) (5) . Thus, it is paramount we develop strategies whereby rheumatic disease patients can be protected from the pandemic virus and its variants. In this letter, we describe a 74-year-old man with seropositive, erosive rheumatoid arthritis (RA), which was initially diagnosed in 1974. He has been treated with hydroxychloroquine 200mg daily, etanercept 25mg weekly, and leflunomide 20mg daily, which has maintained his RA in low disease activity for the last five years. The patient received two doses of the mRNA-1273 vaccine (Moderna) without interruption of his RA treatment, with the second dose administered February 11, 2021. In mid-April, a semiquantitative spike protein receptor binding domain (RBD) antibody level was 53.9 U/mL (reference range: 0-2500 U/mL) and a SARS-CoV-2 anti-spike (S1/RBD) IgG test was negative. An assay designed to detect blocking of the interaction between the SARS-CoV-2 spike protein RBD and the human angiotensin converting enzyme 2 (ACE2) receptor demonstrated <10% blocking activity (6) . An interferon-gamma release assay detecting SARS-CoV-2 specific T cells was also negative (7). The patient and his care team presumed that his suboptimal response to the vaccine was due to the immunosuppressive medications he was taking at the time of vaccination. This article is protected by copyright. All rights reserved anti-spike (S1/RBD) IgG level was positive. The ACE2 blocking assay demonstrated 90-100% blocking activity (Figure 1 ). The interferon-gamma release assay remained negative, suggesting T cell mediated immunity was not achieved. A blunted T cell response to the SARS-CoV-2 vaccine has been demonstrated in patients receiving medications such as methotrexate or tacrolimus, but it has not been evaluated in patients treated with leflunomide to our knowledge (8, 9) . In summary, we describe an immunosuppressed patient with an ineffective immune response after two doses of an mRNA SARS-CoV-2 vaccine, who subsequently achieved a robust antibody response after a booster vaccination with the Johnson & Johnson vaccine, all while continuing his RA medications. Current guidelines put forth by the American College of Rheumatology (ACR) do not recommend obtaining antibody testing after vaccination, in part driven by a lack of clinically meaningful cutoff values for available antibody tests (10) . The ACR does support booster vaccination, after the FDA revised the emergency use authorization for the two mRNA SARS-CoV-2 vaccines to permit a third dosage for certain immunocompromised patients on August 12, 2021 (11) . Our report demonstrates the possibility of achieving humoral immunity against SARS-CoV-2 after initial failure, using a cross-platform booster vaccination strategy. Prior work has demonstrated that heterologous vaccination strategies may induce a more robust immune response in healthy adults (12) (13) (14) . 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