key: cord-0876075-paqdztgd authors: Chilimuri, Sridhar; Mantri, Nikhitha; Zahid, Maleeha; Sun, Haozhe title: COVID-19 vaccine failure in a patient on rituximab therapy date: 2021-06-01 journal: Rheumatol Adv Pract DOI: 10.1093/rap/rkab038 sha: 219ac3228e10c444b439564a9983be6f2bac59b6 doc_id: 876075 cord_uid: paqdztgd nan Key Message: Concurrent rituximab use can result in an ineffective vaccination response to the COVID-19 vaccine. Dear Editor, Severe coronavirus disease 2019 (COVID-19) is a well-recognized cause of morbidity and mortality across rheumatic diseases 1 , and vaccines will play an important role in preventing illness. Immunosuppressive agents are commonly used in the treatment of rheumatologic diseases and among them, anti-CD-20 depleting therapies can result in an impaired humoral response to vaccines 2 . We had previously reported a case of COVID-19 vaccine failure, in a patient on ocrelizumab therapy, an anti-CD19 monoclonal antibody 3 . Here, we report another case of vaccine failure, this time in a patient on Rituximab, an anti-CD20 monoclonal antibody. A 73-year-old Caucasian male presents with nasal congestion, productive cough, myalgias and malaise of four days duration. Five weeks prior, he had completed a two-dose series of the Pfizer-BioNTech COVID-19 vaccine given 21 days apart. He has a history of cryptogenic organizing pneumonia, intermittent asthma, type II diabetes mellitus, hyperlipidemia, and coronary artery disease. He was diagnosed with cryptogenic organizing pneumonia two years earlier, which was initially treated with prednisone and switched to rituximab due to an inadequate treatment response. He was scheduled for intravenous rituximab infusion therapy at a dose of 375 mg/m 2 every six months, and his last dose was administered 10 days after he had received the second dose of the vaccine. His medications included metoprolol succinate, atorvastatin, ezetimibe, metformin, sitagliptin, and a budesonide and formoterol inhaler. There were no known allergies. The patient is retired and lives in New York City. Since the start of the COVID-19 pandemic, he has restricted his participation in social activities, and wore a face mask in public. He denies any history of alcohol, tobacco or illicit drug use. On examination, the patient appeared comfortable. Vitals signs were within normal limits. His respiratory effort and breath sounds were normal, as was the remainder of the physical examination. He tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via a reverse transcription polymerase chain reaction (RT-PCR) nasopharyngeal swab. Given the high risk of progression to severe COVID-19 disease due to his age and comorbidities, bamlanivimab and etesivimab, a monoclonal antibody cocktail against SARS-CoV-2 was administered uneventfully. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Serological testing was performed prior to the monoclonal antibody cocktail infusion with two separate assays, assessing the immunological response to the spike and nucleocapsid protein of SARS-CoV-2, respectively. He tested negative for antibodies to both the spike (S) and nucleocapsid (N) antigens. He reported resolution of his symptoms three days after the infusion. Rituximab is an anti-CD20 monoclonal antibody that binds to the CD20 antigen on the B cell surface, The half-life and prolonged B-cell depleting effects of rituximab makes it challenging to obtain an optimal window for vaccination. T-cell mediated immunity after vaccination could have played a role in the mild nature of his illness, which was not accounted for by only measuring humoral antibody response. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Our case highlights the challenges in vaccinating patients on immunosuppressive drugs. Finding an optimal window and obtaining post vaccination antibody titers may be beneficial. Patients should continue to maintain a high adherence to preventive measures against COVID-19. Further studies are needed to assess the efficacy of COVID-19 vaccine in patients on immunosuppressive therapies. Acknowledgements: All authors had access to the data and a role in writing the manuscript. The patient's consent was obtained for publication. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Data availability statement: Data are available upon reasonable request by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). All data relevant to the study are included in the article. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Factors associated with COVID-19-related death using OpenSAFELY Could anti-CD20 therapy jeopardise the efficacy of a SARS-CoV-2 vaccine? COVID-19 Vaccine Failure in a Patient with Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab ACR COVID-19 Vaccine Clinical Guidance Task Force. COVID-19 Vaccine Clinical Guidance Summary for Patients with Rheumatic and Musculoskeletal Diseases COVID-19 vaccination and antirheumatic therapy Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine Manuscripts submitted to Rheumatology Advances in Practice