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Open accessJournal ArticleDOI: 10.1136/ANNRHEUMDIS-2021-220088

Second COVID-19 infection in a patient with granulomatosis with polyangiitis on rituximab.

04 Mar 2021-Annals of the Rheumatic Diseases (BMJ Publishing Group Ltd)-Vol. 80, Iss: 8, pp 1102-1104
Abstract: Observational data suggest there may be an association between rituximab and severe COVID-19 outcomes.1–3 Anti-CD20 therapies impair humoral response, theoretically increasing the risk of prolonged SARS-CoV-2 infection and shedding, as well as subsequent reinfection. Here, we report a patient with granulomatosis with polyangiitis (GPA) being treated with rituximab who appears to have developed recurrent SARS-CoV-2 infections in the setting of high-risk employment and on recovery ultimately had no detectable SARS-CoV-2 IgG antibodies. This case highlights a potential risk of rituximab in patients with rheumatic disease, which will become especially relevant as rituximab may impair the immunogenicity of SARS-CoV-2 vaccines. A woman in her 30s with a history of limited GPA on rituximab developed COVID-19 twice (figure 1). GPA manifestations have included erosive sinusitis, otitis, saddle nose deformity and orbital pseudotumour. She started rituximab in February 2019. The most recent dose of rituximab 1000 mg was given on 28 September 2020. On 14 August, a disease flare was treated with a 3-week prednisone taper, which completed approximately 4 weeks before COVID-19 infection. She works in an assisted living facility with ongoing staff and resident COVID-19 …

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Open accessJournal ArticleDOI: 10.1136/ANNRHEUMDIS-2021-220382
Abstract: We read with great interest the recent article by Fiedman and Winthrop reporting a patient with granulomatosis with polyangiitis (GPA) being treated with rituximab (RTX), recurrent SARS-CoV-2 disease 2019 (COVID-19) and no detectable SARS-CoV-2 seroresponse after recovery.1 Anti-CD20 therapy impairs humoral response, theoretically increasing the risk of prolonged SARS-CoV-2 infection and shedding as well as subsequent reinfection.1–3 We have recently reported a patient with GPA under maintenance therapy with RTX and SARS-CoV-2 infection.4 Here, we report further details on anti-CD20 therapy with RTX, serological response to SARS-CoV-2 infection, virus elimination and corresponding B cell numbers. This case highlights that B cell numbers in patients with rheumatic diseases treated with RTX could associate with serological response to SARS-CoV-2 infection, which is particularly relevant as RTX may also impair the immunogenicity of SARS-CoV-2 vaccines. An 80-year-old man had received a diagnosis of GPA in 2014 with biopsy-confirmed renal vasculitis and no history of pulmonary manifestation. After remission induction therapy, he received RTX at a dose of 500 mg every 6 months as maintenance therapy. The last …

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Topics: Granulomatosis with polyangiitis (58%), Maintenance therapy (54%), Systemic vasculitis (53%) ... read more

2 Citations


Open accessJournal ArticleDOI: 10.1007/S00296-021-04905-4
Abstract: A 77-year-old man with past medical history of granulomatosis with polyangiitis (GPA) on rituximab and prednisone, presented to the hospital with worsening cough and shortness of breath. He had tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by nasal swab polymerase chain reaction (PCR) while asymptomatic, 6 weeks earlier. He started with cough and shortness of breath 2 weeks after his initial positive test. After developing symptoms, he tested negative twice by nasal swab PCR, but the PCR of his bronchioloalveolar lavage was positive for SARS-CoV-2. He did not develop antibodies against coronavirus. Prednisone 15 mg daily was continued, and he received remdesivir, and convalescent plasma with quick recovery. We reviewed the literature to search for similar cases. Our case suggests that SARS-CoV-2 infection in patients on rituximab may have an atypical presentation and the diagnosis may be delayed due to negative PCR testing in the nasal swab. Patients may benefit from treatment with convalescent plasma.

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Topics: Granulomatosis with polyangiitis (57%), Nasal Swab (55%), Pneumonia (52%)

2 Citations


Open accessJournal ArticleDOI: 10.47360/1995-4484-2021-384-393
05 Sep 2021-
Abstract: In patients with immune-mеdiated (autoimmune) rheumatic diseases (IMIRD), there are a number of factors (advanced age, uncontrolled inflammation, initially irreversible damage to internal organs, comorbid pathology, genetic and other factors) that can potentially lead to an increase in “sensitivity” to SARS-CoV -2 (severe acute respiratory syndrome coronavirus-2) and concomitant viral and bacterial infections, an increase in the risk of a severe course of COVID-19 (coronavirus disease 2019), a decrease in the effectiveness of therapy for both IMIRDs and COVID-19. An important area of pharmacotherapy for IMIRDs and other autoimmune diseases is associated with the use of anti-B-cell drugs, primarily rituximab (RTX), which is a chimeric (mouse/human) monoclonal antibody (mAb) to the CD20 antigen of B cells. At present, in Russia, the RTM biosimilar, acellbia (BIOCAD), is widely used, which is not inferior to RTX in terms of efficiency and safety. The problems of anti-B-cell therapy during the COVID-19 pandemic in relation to the risk of infection, severe course and insufficient effectiveness of vaccination against SARSCoV- 2 are considered. According to the recommendations of the Association of Rheumatologists of Russia, a more rigorous assessment of indications for induction and maintenance therapy of RTX therapy and harmonization of the timing of drug administration and vaccination is required.

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Topics: Rituximab (54%), Pharmacotherapy (54%), Maintenance therapy (53%)

2 Citations


Open accessJournal ArticleDOI: 10.1007/S00296-021-04969-2
Abstract: The outcomes of COVID-19 in patients treated with biologic agents are a subject of intense investigation. Recent data indicated that patients under rituximab (RTX) may carry an increased risk of serious disease. We performed an electronic search in Medline and Scopus using the keywords rituximab and COVID-19. We present a rare case of severe, protracted COVID-19 pneumonia in a patient with mixed connective tissue disease (MCTD) who was infected a few days following RTX treatment. In a relevant literature search, we identified 18 cases of patients with rheumatic diseases (6 RA, 8 ANCA vasculitis, 3 systemic sclerosis and 1 polymyositis) treated with RTX who experienced an atypical and/or prolonged course of COVID-19 pneumonia with no evidence of cytokine storm. Our case indicates that RTX may unfavorably affect outcomes following SARS-CoV-2 infection. B cell depletion may dampen the humoral response against the virus; we may hypothesize that B cell-depleted patients may be protected from cytokine storm but on the other hand may have difficulties in virus clearance leading to a protracted course. Taking into account that COVID-19 vaccines are available we may consider delaying RTX infusions at least in patients without life threatening disease, until vaccination is completed.

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Topics: Rituximab (53%), Pneumonia (52%), Mixed connective tissue disease (50%)

2 Citations


Open accessJournal ArticleDOI: 10.1136/ANNRHEUMDIS-2021-220324
Abstract: In our previous report on antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides (AAV) during the current COVID-19 pandemic, we described our observation of both an incidence-shift with a post-lockdown clustering and an increased incidence rate of AAV diagnoses between February and August 2020 compared with previous years.1 In correspondence to our article, Hocevar et al report how COVID-19 pandemic affected management of patients with vasculitides at their centre. The in-depth analysis examined symptom duration (ie, time eclipsed to final diagnosis), disease activity/severity and seasonal changes of patients presenting with giant cell arteritis, and IgA vasculitis and AAV during 2020 and in the previous decade. No significant differences were found in incidence rates or indications for deferrals; that is, symptoms were experienced for a longer length of time before a diagnosis was made or a more severe presentation occurred.2 As the COVID-19 pandemic remains ongoing, six patients with AAV treated at …

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Topics: Systemic vasculitis (53%), IgA vasculitis (52%)

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Open accessJournal ArticleDOI: 10.1136/ANNRHEUMDIS-2020-217871
Abstract: Objectives COVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease. Methods Case series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed. Results A total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed. Conclusions We found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation.

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540 Citations


Open accessJournal ArticleDOI: 10.1136/ANNRHEUMDIS-2020-218075
Abstract: It is currently unknown whether immunosuppressive and/or immunomodulating agents such as biological disease-modifying antirheumatic drugs (bDMARDs) affect the rate and the outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections of patients with inflammatory rheumatic diseases (IRDs) While several national authorities have defined patients under immunosuppressive therapy as at risk for severe COVID-19,1 accumulating data from individual cases and also from case series, such as a series from Italy published in the Annals of the Rheumatic Diseases by Monti et al 2 and a report about patients with immune-mediated inflammatory diseases from New York,3 suggest that baseline use of bDMARDs is not associated with worse COVID-19 outcome Although the idea of a potentially protective effect of bDMRADs in COVID-19 is intriguing, we feel that extrapolation of these initial data is dangerous and potentially harmful In particular, some caution may have to be applied when employing rituximab (RTX), a B-cell depleting bDMARD, in patients with immune-mediated disease This notion may be illustrated by the following observations: We recently lost two patients with rheumatoid arthritis (RA) treated with RTX to lethal COVID-19 The first patient, a 71-year-old man with rheumatoid factor positive, …

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Topics: Rituximab (52%), Rheumatoid arthritis (52%), Rheumatoid factor (50%)

71 Citations


Open accessJournal ArticleDOI: 10.1093/CID/CIAB048
Abstract: Background Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution and public health level decision-making. The numbers of available SARS-CoV-2 nucleic acid detection tests are rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance. Objective The IDSA's goal was to develop an evidence-based diagnostic guideline to assist clinicians, clinical laboratorians, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss the nuance of test result interpretation in a variety of practice settings and highlight important unmet research needs in the COVID-19 diagnostic testing space. Methods IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. Results The panel agreed on 17 diagnostic recommendations. Conclusions Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered moderate to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals with known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions, dictate eligibility for surgery, or inform solid organ or hematopoietic stem cell transplantation timing. Ultimately, prioritization of testing will depend on institutional-specific resources and the needs of different patient populations.

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Topics: Systematic review (51%)

47 Citations


Open accessJournal ArticleDOI: 10.1186/S13045-020-00968-1
Abstract: SARS-CoV-2 has infected millions of people worldwide, but little is known at this time about second infections or reactivation. Here, we report a case of a 55-year-old female undergoing treatment for CD20+ B cell acute lymphoblastic leukemia who experienced a viral reactivation after receiving rituximab, cytarabine, and dasatinib. She was initially hospitalized with COVID-19 in April and developed a high antibody titer with two negative nasal polymerase chain reaction (PCR) swabs for SARS-CoV-2 on discharge. After recovery, she resumed treatment in June for her leukemia, which included rituximab, cytarabine, and dasatinib. She promptly lost her COVID-19 antibodies, and her nasal PCR turned positive in June. She developed a severe COVID-19 pneumonia with lymphopenia, high inflammatory markers, and characteristic bilateral ground-glass opacities on chest CT, requiring high-flow nasal cannula and transfer to the intensive care unit. She received steroids, anticoagulation, and convalescent plasma, and within 48 h she was off oxygen. She was discharged home in stable condition several days later. Given the short time frame from leukemia treatment to PCR positivity and the low case rate in mid-June in New York City, reinfection appears to have been unlikely and SARS-CoV-2 reactivation is a possible explanation. This case illustrates the risks of treating recently recovered COVID-19 patients with immunosuppressive therapy, particularly lymphocyte- and antibody-depleting therapy, and raises new questions about the potential of SARS-CoV-2 reactivation.

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Topics: Leukemia (52%), Dasatinib (52%), Rituximab (51%) ... read more

46 Citations


Open accessJournal ArticleDOI: 10.1007/S00296-020-04699-X
Abstract: The objective of this study is to describe the characteristics and outcomes of rheumatic and musculoskeletal disease (RMD) patients who were treated with rituximab and had suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this descriptive study, RMD patients who were treated with rituximab in the last 12 months at the Rheumatology Department of our hospital were screened for SARS-CoV-2 infection via telephone interview and a comprehensive review of clinical health records (01/02/2020-26/05/2020). Those with probable or confirmed SARS-CoV-2 infection were included. In total, 76 patients were screened. Of these, 13 (17.1%) had suspected or confirmed SARS-CoV-2 infection. With regard to these 13 patients, the median age at coronavirus disease (COVID-19) diagnosis was 68 years (range 28-76 years) and 8 (61.5%) were female. Five patients had rheumatoid arthritis, three had systemic vasculitis, two had Sjogren syndrome, and two had systemic lupus erythematosus. Additionally, seven patients (53.8%) had pulmonary involvement secondary to RMD. Eight patients (61.5%) developed severe disease leading to hospitalization, and seven developed bilateral pneumonia and respiratory insufficiency. Of the eight hospitalized patients, five (62.5%) fulfilled the acute respiratory distress syndrome criteria and three developed a critical disease and died. Our cohort had a high rate of severe disease requiring hospitalization (61.5%), with bilateral pneumonia and hyperinflammation leading to a high mortality rate (23.1%). Treatment with rituximab should be considered a possible risk factor for unfavorable outcomes in COVID-19 patients with RMD. However, further study is required to confirm this association.

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Topics: Rituximab (54%), Rheumatology (51%), Risk factor (51%) ... read more

46 Citations