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
TL;DR: In this article, the authors 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 CoV2 IgG antibodies.
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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TL;DR: In this article, the authors describe the presentation and complications, including relapses, of COVID-19 in patients under anti-CD20 treatments, and describe viral clearance and determine the safety of reintroducing antiCD20 treatment.
Abstract: Background Our objective is to describe the presentation and complications, including relapses, of COVID-19 in patients under anti-CD20 treatments. In addition, to describe viral clearance and determine the safety of reintroducing anti-CD20 treatment. Methods Retrospective cohort study of 422 patients under anti-CD20 treatment that was administered from January 1, 2019, to December 31, 2020. Results Fifty-seven patients were diagnosed of COVID-19 (13.5%). 25 patients (43.9%) required hospital admission. 5 patients died (8.8%), 10 developed severe COVID-19 and acute respiratory distress syndrome. Mortality rate was higher among patients infected during the first 3 months following the last dose of anti-CD20 (14.7% vs 0%, p=0,046).The median time of persistence of positive RT-PCR was 22 days (IQR 13-40). Nine out of 52 survivors (17.3%) presented relapses. All of them received the last dose of anti-CD20 less than 6 months before the COVID-19 episode. Clinical presentation was fever (n=8; 88.9%), dyspnea (n=7; 77.8%), cough (n=7; 77.8%), worsening of previous infiltrates (n=5; 55.6%) and new pulmonary infiltrates (n=8; 88.9%). An increase in lymphocytes with CD4/CD8 ratio inversion was observed in all cases. Among the 25 patients who resumed anti-CD20 drug, 4 (16.0%) presented relapses vs 5/28 among those who did not (17.9%), (p=0.857). Conclusion Patients infected with SARS-CoV-2 during the 6 months after anti-CD20 administration had a worse outcome and a higher mortality rate. The duration of infectivity may be longer. Relapses of COVID-19 occurred in more than 15% and were associated with viral replication. Once the infection is resolved, it is safe to restart treatment with anti-CD20.
33 citations
TL;DR: In this article , the authors describe the clinical, immunological, and virological course of a patient with eosinophilic granulomatosis with polyangiitis, who developed the status of long-term asymptomatic SARS-CoV-2 carrier for more than 7 months.
Abstract: Abstract Purpose SARS-CoV-2 infection in immunocompromised hosts is challenging, and prolonged viral shedding can be a common complication in these patients. We describe the clinical, immunological, and virological course of a patient with eosinophilic granulomatosis with polyangiitis, who developed the status of long-term asymptomatic SARS-CoV-2 carrier for more than 7 months. Methods Over the study period, the patient underwent 20 RT-PCR tests for SARS-CoV-2 detection on nasopharyngeal swabs. In addition, viral cultures and genetic investigation of SARS-CoV-2 were performed. As for immunological assessment, serological and specific T-cell testing was provided at different time points. Results Despite the patient showing a deep drug-induced B and T adaptive immunity impairment, he did not experience COVID-19 progression to severe complications, and the infection remained asymptomatic during the follow-up period, but he was not able to achieve viral clearance for more than 7 months. The infection was finally cleared by SARS-CoV-2-specific monoclonal antibody treatment, after that remdesivir and convalescent plasma failed in this scope. The genetic investigations evidenced that the infection was sustained by multiple viral subpopulations that had apparently evolved intra-host during the infection. Conclusion Our case suggests that people with highly impaired B- and T-cell adaptive immunity can prevent COVID-19 progression to severe complications, but they may not be able to clear SARS-CoV-2 infection. Immunocompromised hosts with a long-term infection may play a role in the emergence of viral variants.
13 citations
TL;DR: In this paper, a case of severe, protracted COVID-19 pneumonia in a patient with mixed connective tissue disease (MCTD) who was infected a few days following rituximab (RTX) treatment was presented.
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.
12 citations
TL;DR: In this paper, the authors reviewed the current data on infections associated with rituximab use published over the last 5 years and found that higher risk of infection in patients with underlying rheumatologic diseases was seen in those who required a therapy switch and had a smoking history.
Abstract: We reviewed the current data on infections associated with rituximab use published over the last 5 years. New literature was available on rates of serious infections, Hepatitis B reactivation and screening, and infection with Severe Acute Respiratory Syndrome Coronavirus 2. Rates of infection varied by study and population, however, higher risk of infection in patients with underlying rheumatologic diseases was seen in those who required a therapy switch, had a smoking history, and those undergoing retreatment who had a serious infection with their first course of therapy. With regards to HBV, the proportion of patients screened continues to be inadequate. Despite the upfront cost, HBV screening and prophylaxis were found to be cost effective. There is still limited data regarding COVID-19 severity in the setting of rituximab, however, rituximab, especially in combination with steroids, may lead to more severe disease and higher mortality.
11 citations
TL;DR: A 77-year-old man with past medical history of granulomatosis with polyangiitis on rituximab and prednisone, presented to the hospital with worsening cough and shortness of breath.
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.
8 citations
References
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University of California, San Francisco1, University of Alabama at Birmingham2, University of Alabama3, Stanford University4, University of Washington5, Institute of Chartered Accountants of Nigeria6, University of Otago7, Harvard University8, Boston Children's Hospital9, McMaster University10, HealthPartners11, Royal Brisbane and Women's Hospital12, University of Queensland13
TL;DR: It is found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds ofospitalisation in patients with rheumatic disease.
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.
883 citations
University of Utah1, Brown University2, University of Texas at Austin3, Rush University Medical Center4, Seattle Children's Research Institute5, Duke University6, McMaster University7, Mayo Clinic8, University of Kansas9, Washington University in St. Louis10, Emory University11, Case Western Reserve University12, Vancouver General Hospital13, University of Minnesota14, Cleveland Clinic15
TL;DR: The IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19, and testing is recommended for asymptomatic individuals with known or suspected contact with a CO VID-19 case.
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.
137 citations
TL;DR: Accumulating data suggest that baseline use of bDMARDs is not associated with worse COVID-19 outcome and that some caution may have to be applied when employing rituximab (RTX), a B-cell depleting b DMARD, in patients with immune-mediated disease.
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, …
110 citations
TL;DR: Treatment with rituximab should be considered a possible risk factor for unfavorable outcomes in COVID-19 patients with RMD, with a high rate of severe disease requiring hospitalization and a high mortality rate.
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.
83 citations
TL;DR: 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.
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.
73 citations