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1.
Int J Infect Dis ; 121: 85-88, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1873077

ABSTRACT

Although messenger ribonucleic acid vaccines are substantially effective toward SARS-CoV-2 infection, patients with hematologic malignancies are still prone to the virus. Herein, we report a fatal case of breakthrough SARS-CoV-2 Delta variant infection in a patient with mucosa-associated lymphoid tissue lymphoma with remission by bendamustine-rituximab (BR) therapy completed a year ago. The serologic study revealed impaired responsiveness toward vaccines and prolonged high viral load after infection. BR therapy seemingly induced an immune escape. Prevention and treatment strategies for such vulnerable patients should be clarified immediately.


Subject(s)
COVID-19 , SARS-CoV-2 , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bendamustine Hydrochloride/adverse effects , COVID-19/drug therapy , Humans , Rituximab/adverse effects
3.
Perm J ; 26(1): 123-131, 2021 Oct 29.
Article in English | MEDLINE | ID: covidwho-1863290

ABSTRACT

INTRODUCTION: Relapsing COVID-19 infections have been reported, but their etiology and severity are still unknown. In addition, there have been no cases in the literature that associate relapsing infection with immunosuppression, either from a disease course or medications. CASE PRESENTATION: This case series illustrates two patients who developed a relapsed infection, likely from recent rituximab infusions. In addition, both cases depicted a severe form of infection than the initial one. Laboratory investigations revealed these patients were unable to produce COVID-19 antibodies, even though one of the patients received convalescent plasma. CONCLUSION: Clinicians should be aware of the possibility of relapsing COVID-19, especially in immunosuppressed patients. Because rituximab induces B-cell depletion, it can also decrease the effectiveness of the COVID-19 vaccine. Therefore, these patients should receive the vaccine before their scheduled rituximab infusion.


Subject(s)
COVID-19 , Immunosuppressive Agents , Rituximab , COVID-19/diagnosis , COVID-19 Vaccines , Humans , Immunization, Passive , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Recurrence , Rituximab/adverse effects , Rituximab/therapeutic use , Treatment Outcome
4.
J Infect Chemother ; 28(7): 971-974, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1828865

ABSTRACT

Corticosteroids are widely used to treat severe COVID-19, but in immunocompromised individuals, who are susceptible to persistent infection, long term corticosteroid use may delay viral clearance. We present a case of prolonged SARS-CoV-2 infection in a man with significantly impaired B-cell immunity due to non-Hodgkin lymphoma which had been treated with rituximab. SARS-CoV-2 shedding persisted, despite treatment with remdesivir. Viral sequencing confirmed the persistence of the same viral strain, ruling out the possibility of reinfection. Although SARS-CoV-2 IgG, IgA and IgM remained negative throughout the treatment period, after reduction of the corticosteroid dose, PCR became negative. Long-term corticosteroid treatment, especially in immunocompromised individuals, may result in suppression of cell-mediated immunity and prolonged SARS-CoV-2 infection.


Subject(s)
COVID-19 , Antibodies, Viral , COVID-19/drug therapy , Humans , Immunocompromised Host , Male , Rituximab/adverse effects , SARS-CoV-2
5.
J Infect Chemother ; 28(6): 810-813, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1828862

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is detectable in nasopharyngeal specimens for up to 12-20 days regardless of the presence of chronic diseases in patients. We report a case of prolonged SARS-CoV-2 infection that lasted for more than eight weeks. The patient had persistent lymphopenia after receiving six cycles of bendamustine and rituximab (BR) therapy for follicular lymphoma; the last chemotherapy session was completed nine months before admission. The first nasopharyngeal specimen (NPS) for the SARS-CoV-2 polymerase chain reaction assay tested positive for the N501Y variant five weeks before admission. The patient's general and respiratory conditions gradually worsened; therefore, he was admitted to our hospital, and the same SARS-CoV-2 variant was subsequently identified on admission. Treatment for coronavirus disease was initiated, and the patient's condition improved; however, the NPS tested positive on day 15. The patient was discharged on day 28 and was instructed to isolate at home for a month. Hence, possible prolonged SARS-CoV-2 shedding should be considered in patients who receive BR therapy.


Subject(s)
COVID-19 , SARS-CoV-2 , Bendamustine Hydrochloride/therapeutic use , COVID-19/drug therapy , Humans , Male , RNA, Viral , Rituximab/adverse effects , Virus Shedding
6.
Rev Esp Quimioter ; 35(1): 260-264, 2022 Apr.
Article in Spanish | MEDLINE | ID: covidwho-1732682

ABSTRACT

OBJECTIVE: Rituximab-induced immunosuppression could be a risk factor for mortality from COVID-19. The aim of the study was to describe the prevalence of SARS-CoV-2 infection in patients who have received rituximab and its association with a persistent viral infection. METHODS: Retrospective observational study of patients who received rituximab in the 6 months before to the onset of the pandemic. We analyzed the presence of infection and associated them with demographic variables, pathological history related to an increased risk of developing severe COVID-19, the doses of rituximab received, the type of ventilatory support, thromboembolic events, and the treatment received. A descriptive analysis of all the variables was carried out and infected and uninfected patients were compared. RESULTS: We screened a total of 68 patients who had received rituximab (median cumulative dose: 4,161mg (2,611-8,187.5)). 54.4% men, mean age 60.8 years (15.7; 25-87)). C + was confirmed for 22 patients. Of these, 45.5% had high blood pressure, 36.4% Diabetes Mellitus, 31.8% smokers/ex-smoker, 22.7% lung disease, 13.6% heart disease and 4.5% obesity. There were no statistically significant differences between C+ and C-. Only 2 patients developed immunity. For 10 patients (45.5%) did not have a negative CRP until the end of the follow-up. There was no association with cumulative dose of rituximab. The mortality rate was 22.7% in the C+. CONCLUSIONS: We observe that the persistence of the infection leads to a worse evolution of COVID-19. The use of alternatives should be considered during the pandemic, because of patients with decreased B-cell function may have high risk of fatal progression from COVID-19.


Subject(s)
COVID-19 , COVID-19/drug therapy , Female , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , Rituximab/adverse effects , SARS-CoV-2
7.
Dermatol Ther ; 35(5): e15417, 2022 May.
Article in English | MEDLINE | ID: covidwho-1731138

ABSTRACT

There are safety concerns in the treatment of pemphigus patients with immunosuppressants, particularly rituximab (RTX), in times of the COVID-19 pandemic. In the beginning, the reports were more pessimistic. However, few reports have recently pointed to manageable courses in this patient group. Therefore, we investigated the disease characteristics and demographic features of pemphigus patients in the period of the COVID-19 pandemic. We aimed to investigate the impact of immunosuppressants on the course of COVID-19 in pemphigus patients. Also, we tried to find out the rate of flares due to COVID-19 and SARS-Cov-2 vaccines. This multicenter study included 247 patients with pemphigus from three tertiary dermatology clinics with the specialized outpatient clinic for autoimmune blistering diseases. Patients were asked standardized questions in person or via telephone calls. Also, demographic data were collected from patients' files. Two hundred forty-four of 247 patients took the survey between August and September 2021. The data of three patients were obtained from the National Health System. We collected the data of all pemphigus patients who visited the clinics at least once in the past 3 years. Among 51 patients having COVID-19, 40 had a non-serious disease, whereas 11 required hospitalization. One patient died because of COVID-19 infection. The number of patients is limited, and data depends mainly on patients' statements. RTX treatment does not require additional safety cautions than other immunosuppressives.


Subject(s)
Autoimmune Diseases , COVID-19 , Pemphigus , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunosuppressive Agents/adverse effects , Pandemics , Pemphigus/chemically induced , Pemphigus/drug therapy , Pemphigus/epidemiology , Rituximab/adverse effects , SARS-CoV-2 , Treatment Outcome
8.
Br J Clin Pharmacol ; 88(6): 2969-2972, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1672996

ABSTRACT

Mild encephalopathy with a reversible splenial lesion syndrome (MERS) is a rare clinico-radiological entity. Rituximab (RTX)-induced MERS has never been described before. Herein, we report the case of a 33-year-old patient diagnosed since 2017, with an IgG4-related disease (IgG4-RD). This diagnosis was retained in the face of a prolonged fever, sicca syndrome, hepatic damage and renal pseudotumour associated to a high level of IGg4 at 2.8 g/L with suggestive renal histology. The patient was treated with corticosteroid therapy with persistence of renal impairment and nephrotic syndrome indicating RTX therapy. The patient received his first dose of RTX and presented neurological and respiratory impairments a few hours afterwards. An infectious investigation comprising a SARS CoV-2 PCR and viral PCRs (VZV, herpes and CMV) on cerebrospinal fluid (CSF) were negative. The HBV, HCV, HIV, Parvo B19, CMV, EBV, herpes, mycoplasma and syphilis serologies as well as Legionella antigenuria were also negative. The patient had received intravenous immunoglobulins (IVIG) and methylprednisone, associated with sodium valproate with favourable outcome. The diagnosis of MERS induced by RTX was retained in our patient according to clinical and radiological features. We herein report the first case of MERS following RTX in a patient treated for IgG4-RD.


Subject(s)
Brain Diseases , COVID-19 , Cytomegalovirus Infections , Drug-Related Side Effects and Adverse Reactions , Encephalitis , Immunoglobulin G4-Related Disease , Adult , Brain Diseases/chemically induced , Brain Diseases/complications , Brain Diseases/diagnosis , Corpus Callosum/diagnostic imaging , Corpus Callosum/pathology , Encephalitis/complications , Encephalitis/diagnosis , Encephalitis/pathology , Humans , Immunoglobulin G4-Related Disease/complications , Immunoglobulin G4-Related Disease/pathology , Magnetic Resonance Imaging , Rituximab/adverse effects
9.
Postgrad Med ; 134(2): 239-243, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1671777

ABSTRACT

INTRODUCTION: The risk of developing severe COVID-19 illness despite completing vaccination for patients who have previously received immunosuppressive therapy is unclear. CASE PRESENTATION: We present three patients who received rituximab for treatment of autoimmune disorders who subsequently developed severe COVID-19 pneumonia post-vaccination requiring intensive care unit admission and found to have undetectable B cells. DISCUSSION: While there have been concerns about the effectiveness of COVID-19 vaccines in this patient cohort, this is the first case series to report development of severe COVID-19 illness after completing vaccination in those who previously received rituximab. Guidelines for the optimal timing of COVID-19 vaccination in relation to immunosuppressive therapy have been recently published, albeit after many patients in this subpopulation have already been vaccinated. CONCLUSION: This case series brings attention to the limited humoral response to vaccines in patients treated with rituximab, highlights existing guidelines and their limitations, and raises future considerations about the potential benefits to testing vaccine responsiveness.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19 Vaccines/adverse effects , Humans , Rituximab/adverse effects , SARS-CoV-2 , Vaccination
11.
J Autoimmun ; 125: 102743, 2021 12.
Article in English | MEDLINE | ID: covidwho-1568811

ABSTRACT

OBJECTIVES: To investigate humoral responses and safety of mRNA SARS-CoV-2 vaccines in systemic autoimmune and autoinflammatory rheumatic disease (SAARD) patients subjected or not to treatment modifications during vaccination. METHODS: A nationwide, multicenter study, including 605 SAARD patients and 116 controls, prospectively evaluated serum anti-SARS-CoV-2 S1-protein IgG antibody titers, side-effects, and disease activity, one month after complete vaccination, in terms of distinct treatment modification strategies (none, partial and extended modifications). Independent risk factors associated with hampered humoral responses were identified by data-driven multivariable logistic regression analysis. RESULTS: Patients with extended treatment modifications responded to vaccines similarly to controls as well as SAARD patients without immunosuppressive therapy (97.56% vs 100%, p = 0.2468 and 97.56% vs 97.46%, p > 0.9999, respectively). In contrast, patients with partial or without therapeutic modifications responded in 87.50% and 84.50%, respectively. Furthermore, SAARD patients with extended treatment modifications developed higher anti-SARS-CoV-2 antibody levels compared to those without or with partial modifications (median:7.90 vs 7.06 vs 7.1, p = 0.0003 and p = 0.0195, respectively). Mycophenolate mofetil (MMF), rituximab (RTX) and methotrexate (MTX) negatively affected anti-SARS-CoV-2 humoral responses. In 10.5% of vaccinated patients, mild clinical deterioration was noted; however, no differences in the incidence of deterioration were observed among the distinct treatment modification SAARD subgroups. Side-effects were generally comparable between SAARD patients and controls. CONCLUSIONS: In SAARD patients, mRNA SARS-CoV-2 vaccines are effective and safe, both in terms of side-effects and disease flares. Treatment with MMF, RTX and/or MTX compromises anti-SARS-CoV-2 antibody responses, which are restored upon extended treatment modifications without affecting disease activity.


Subject(s)
/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Autoimmune Diseases/immunology , Hereditary Autoinflammatory Diseases/immunology , Rheumatic Diseases/immunology , /adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Autoimmune Diseases/drug therapy , COVID-19/prevention & control , Female , Greece , Hereditary Autoinflammatory Diseases/drug therapy , Humans , Immunoglobulin G/blood , Male , Methotrexate/adverse effects , Methotrexate/therapeutic use , Middle Aged , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Prospective Studies , Rheumatic Diseases/drug therapy , Rituximab/adverse effects , Rituximab/therapeutic use , SARS-CoV-2/immunology , Young Adult
12.
Ann Rheum Dis ; 81(3): 422-432, 2022 03.
Article in English | MEDLINE | ID: covidwho-1560917

ABSTRACT

OBJECTIVES: Perform a systematic literature review (SLR) on risk and prognosis of SARS-CoV-2 infection and vaccination against SARS-CoV-2 in patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: Literature was searched up to 31 May 2021, including (randomised) controlled trials and observational studies with patients with RMD. Pending quality assessment, data extraction was performed and risk of bias (RoB) was assessed. Quality assessment required provision of (1) an appropriate COVID-19 case definition, and (2a) a base incidence (for incidence data) or (2b) a comparator, >10 cases with the outcome and risk estimates minimally adjusted for age, sex and comorbidities (for risk factor data). RESULTS: Of 5165 records, 208 were included, of which 90 passed quality assessment and data were extracted for incidence (n=42), risk factor (n=42) or vaccination (n=14). Most studies had unclear/high RoB. Generally, patients with RMDs do not face more risk of contracting SARS-CoV-2 (n=26 studies) or worse prognosis of COVID-19 (n=14) than individuals without RMDs. No consistent differences in risk of developing (severe) COVID-19 were found between different RMDs (n=19). Disease activity is associated with worse COVID-19 prognosis (n=2), possibly explaining the increased risk seen for glucocorticoid use (n=13). Rituximab is associated with worse COVID-19 prognosis (n=7) and possibly Janus kinase inhibitors (n=3). Vaccination is generally immunogenic, though antibody responses are lower than in controls. Vaccine immunogenicity is negatively associated with older age, rituximab and mycophenolate. CONCLUSION: This SLR informed the July 2021 update of the European Alliance of Associations for Rheumatology recommendations for the management of RMDs in the context of SARS-CoV-2.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/mortality , Musculoskeletal Diseases/virology , Rheumatic Diseases/virology , SARS-CoV-2/immunology , Adult , COVID-19/immunology , COVID-19/prevention & control , Female , Glucocorticoids/adverse effects , Humans , Immunogenicity, Vaccine/drug effects , Immunosuppressive Agents/adverse effects , Incidence , Janus Kinase Inhibitors/adverse effects , Male , Middle Aged , Musculoskeletal Diseases/drug therapy , Prognosis , Rheumatic Diseases/drug therapy , Risk Factors , Rituximab/adverse effects
13.
RMD Open ; 7(3)2021 12.
Article in English | MEDLINE | ID: covidwho-1551051

ABSTRACT

OBJECTIVE: To determine whether patients with inflammatory autoimmune diseases treated with rituximab (RTX) have more severe forms of COVID-19 compared with patients treated with anticytokine therapies, such as Tumour Necrosis Factor (TNF) inhibitors. METHODS: We included all patients who were on either RTX or infliximab (IFX) in two Swiss cantons during the first wave of the COVID-19 pandemic. We collected self-reported symptoms compatible with COVID-19, PCR-confirmed diagnoses of COVID-19 and the evolution of COVID-19 infections. We computed the raw and propensity score-adjusted incidence of COVID-19 by treatment group. RESULTS: 190 patients were enrolled, of whom 121 (64%) were in the RTX group and 69 (36%) were in the IFX group. Twenty-one patients (11%) reported symptoms compatible with COVID-19 (RTX: 10, IFX: 11, p=0.14). Among patients with COVID-19 symptoms, four developed severe forms of the disease, with life-threatening pulmonary manifestations requiring intensive mechanical ventilation (RTX: 4 of 10, IFX: 0 of 11, Fisher's exact test p=0.04). The incidence rate of COVID-19 symptoms was 0.73 (95% CI 0.39 to 1.37) cases per 1000 patient-days on RTX vs 1.52 (95% CI 0.82 to 2.85) cases per 1000 patient-days on IFX (crude p=0.10, adjusted p=0.07). The incidence rate of severe COVID-19 was 0.28 (95% CI 0.08 to 0.7.2) cases per 1000 patient-days on RTX compared with null on IFX (95% CI 0.0 to 0.44) (p=0.13). A replication in an independent validation cohort confirmed these findings, with consistent results in the Swiss Clinical Quality Management registry. CONCLUSION: While the incidence of symptoms compatible with COVID-19 was overall similar in patients receiving RTX or IFX, the incidence of severe COVID-19 tended to be higher in the RTX group.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , COVID-19 , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Humans , Incidence , Infliximab/adverse effects , Pandemics , Rituximab/adverse effects , SARS-CoV-2
15.
Dermatol Ther ; 35(1): e15216, 2022 01.
Article in English | MEDLINE | ID: covidwho-1528369

ABSTRACT

SARS-COV2 vaccines were approved without long-term monitoring due to emergent situations. This has raised some issues about the timing and protocol of receiving vaccines in specific situations such as patients receiving immunomodulatory agents including rituximab, which is widely used for various disorders such as multiple sclerosis, pemphigus, and many rheumatologic disorders. We described two cases of pemphigus vulgaris (a new case and one with flare-up) following vaccination with Astrazeneca in Iran and reviewed the existing data in this regard through searching on PubMed, Google Scholar, and Scopus. All of the relevant papers published until June 28, 2021, which we could access their full-texts were included. We found some recommendations made by rheumatologists, neurologists, and dermatologists in regard to vaccination timing in this group of patients and tried to summarize them to provide a practical guide for clinicians. Clinicians should perform a careful, individualized risk-benefit assessment for their patients and consider a delay in rituximab administration after completion of COVID vaccination if there is not any considerable risk of disease relapse or organ failure. Moreover, choosing vaccines with potential of providing protection after single dose, especially in countries with limited access to vaccines may be a reasonable approach.


Subject(s)
COVID-19 , Pemphigus , COVID-19 Vaccines , Humans , Iran , Pemphigus/diagnosis , Pemphigus/drug therapy , RNA, Viral , Rituximab/adverse effects , SARS-CoV-2 , Vaccination
16.
Neurology ; 97(19): e1870-e1885, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1523377

ABSTRACT

BACKGROUND AND OBJECTIVES: People with multiple sclerosis (MS) are a vulnerable group for severe coronavirus disease 2019 (COVID-19), particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. METHODS: Data from 12 data sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs) covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit (ICU) admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale (EDSS) score. RESULTS: Six hundred fifty-seven (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01-2.41; aOR 2.43, 95% CI 1.48-4.02) and ICU admission (aOR 2.30, 95% CI 0.98-5.39; aOR 3.93, 95% CI 1.56-9.89), although only rituximab was associated with higher risk of artificial ventilation (aOR 4.00, 95% CI 1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization (aOR 1.75, 95% CI 1.29-2.38; aOR 2.76, 95% CI 1.87-4.07) and ICU admission (aOR 2.55, 95% CI 1.49-4.36; aOR 4.32, 95% CI 2.27-8.23), but only rituximab was associated with artificial ventilation (aOR 6.15, 95% CI 3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization (aOR 1.86, 95% CI 1.13-3.07; aOR 2.88, 95% CI 1.68-4.92) and ICU admission (aOR 2.13, 95% CI 0.85-5.35; aOR 3.23, 95% CI 1.17-8.91), but only rituximab was associated with ventilation (aOR 5.52, 95% CI 1.71-17.84). Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity. DISCUSSION: Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19.


Subject(s)
COVID-19/complications , Hospitalization/statistics & numerical data , Multiple Sclerosis/complications , Multiple Sclerosis/drug therapy , Adolescent , Adult , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/pathology , COVID-19/physiopathology , Cross-Sectional Studies , Dimethyl Fumarate/adverse effects , Dimethyl Fumarate/therapeutic use , Female , Humans , Male , Middle Aged , Natalizumab/adverse effects , Natalizumab/therapeutic use , Respiration, Artificial/statistics & numerical data , Rituximab/adverse effects , Rituximab/therapeutic use , SARS-CoV-2 , Young Adult
17.
Cancer Cell ; 40(1): 3-5, 2022 01 10.
Article in English | MEDLINE | ID: covidwho-1517077

ABSTRACT

Anti-COVID-19 immunity dynamics were assessed in patients with cancer in a prospective clinical trial. Waning of immunity was detected 4-6 months post-vaccination with significant increases in anti-spike IgG titers after booster dosing, and 56% of seronegative patients seroconverted post-booster vaccination. Prior anti-CD20/BTK inhibitor therapy was associated with reduced vaccine efficacy.


Subject(s)
Antibodies, Viral/biosynthesis , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunization, Secondary , Immunoglobulin G/biosynthesis , Neoplasms/immunology , SARS-CoV-2/immunology , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antigens, Viral/immunology , COVID-19/complications , COVID-19/immunology , Follow-Up Studies , Humans , Immunocompromised Host , Immunogenicity, Vaccine , Immunoglobulin G/blood , Immunoglobulin G/immunology , Neoplasms/complications , Neoplasms/drug therapy , Prospective Studies , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Rituximab/adverse effects , Rituximab/therapeutic use , Seroconversion , Spike Glycoprotein, Coronavirus/immunology , Vaccination
18.
Ann Rheum Dis ; 80(12): 1537-1544, 2021 12.
Article in English | MEDLINE | ID: covidwho-1515258

ABSTRACT

OBJECTIVES: The monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses. METHODS: CD8+ T cell expansion was studied in rituximab-treated rheumatoid arthritis (RA) patients and B cell-deficient mice on vaccination/infection with different vaccines/pathogens. RESULTS: Rituximab-treated RA patients vaccinated with Influvac showed reduced expansion of influenza-specific CD8+ T cells when compared with healthy controls. Moreover, B cell-deficient JHT mice infected with mouse-adapted Influenza or modified vaccinia virus Ankara showed less vigorous expansion of virus-specific CD8+ T cells than wild type mice. Of note, JHT mice do not have an intrinsic impairment of CD8+ T cell expansion, since infection with vaccinia virus induced similar T cell expansion in JHT and wild type mice. Direct type I interferon receptor signalling of B cells was necessary to induce several chemokines in B cells and to support T cell help by enhancing the expression of MHC-I. CONCLUSIONS: Depending on the stimulus, B cells can modulate CD8+ T cell responses. Thus, B cell depletion causes a deficiency of de novo antibody responses and affects the efficacy of cellular response including cytotoxic T cells. The choice of the appropriate vaccine to vaccinate B cell-depleted patients has to be re-evaluated in order to efficiently induce protective CD8+ T cell responses.


Subject(s)
Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , B-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Immunogenicity, Vaccine/immunology , Influenza Vaccines/immunology , Interferon Type I/immunology , Rituximab/adverse effects , Animals , Case-Control Studies , Cytokines/immunology , Histocompatibility Antigens Class I/immunology , Humans , Influenza Vaccines/therapeutic use , Influenza, Human/prevention & control , Mice , Orthomyxoviridae/immunology , Orthomyxoviridae Infections/immunology , Vaccinia/immunology , Vaccinia virus/immunology
19.
Mult Scler Relat Disord ; 57: 103371, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1510132

ABSTRACT

BACKGROUND: Outcomes of COVID-19 in PwMS (persons with Multiple Sclerosis) on immunosuppressive therapies, particularly B-cell depletors, can be unpredictable. There has been a concern for postponing or avoiding use of Rituximab (RTX) during the COVID-19 pandemic. We report the course and outcomes of COVID-19 in PwMS receiving RTX. METHODS: PwMS receiving RTX who contracted COVID-19 were closely monitored by tele-consultation and/or evaluated during hospital visits. Those requiring hospitalization for oxygen therapy or admission to ICU or expiring due to COVID-19 were considered to have severe disease. Those without desaturation and manageable at home were considered to have mild disease. Disease course and outcomes were noted. RESULTS: Twelve out of 62 (19.4%) PwMS on RTX therapy developed COVID-19. Four (age 35-49 years; mean 43.5) had severe COVID; three of whom had Secondary Progressive MS (SPMS). One PwMS expired. Two had prolonged fever lasting >1 month. One demonstrated features of SARS-CoV-2 reactivation. Interval from last RTX infusion (average dose 750 mg) to COVID-19 onset ranged 1-4 (mean 3.7) months. Eight PwMS had mild COVID-19 (age 26-54 years; mean 37.7); six had RRMS and two SPMS. RTX dose was lower (average dose 625 mg) and infusion to COVID-19 onset duration was longer, ranging 4-20 (mean 9.5) months. Four patients, two each from mild and severe COVID-19 groups had neurological deterioration, but none had true relapses. CONCLUSION: RTX treated PwMS may have unpredictable disease outcomes if they contract COVID-19, but may be at risk of severe disease and persistent infection. In our series higher age, SPMS, shorter interval from RTX infusion to COVID-19 onset and higher dose of RTX were noted amongst those developing severe disease. RTX should be use cautiously during the COVID-19 pandemic and if unavoidable, less frequent and lower doses should be considered. Patients receiving RTX must be counselled to follow strict COVID-19 preventive measures.


Subject(s)
COVID-19 , Multiple Sclerosis , Adult , Humans , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Pandemics , Rituximab/adverse effects , SARS-CoV-2
20.
BMJ Case Rep ; 14(10)2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1495129

ABSTRACT

Rituximab (RTX) is a monoclonal anti-CD20 antibody used to treat non-Hodgkin's lymphoma. RTX-organising pneumonia (RTX-OP) is a rare complication following treatment with RTX. We report a 49-year-old woman, with CD5-negative B-cell lymphoproliferative disorder who developed high-grade fever, dyspnoea and dry cough 3 days after the first dose of RTX. She responded poorly to antibiotics and antifungal therapy. High-resolution CT (HRCT) of the chest revealed bilateral patchy ground-glass opacities with arcade-like signs suggestive of OP. She was pulsed with intravenous methylprednisolone and RTX was discontinued. She was able to be weaned off the non-invasive ventilation (NIV) support and was discharged with maintenance prednisolone 1 mg/kg and tapered over 6 weeks. A repeated HRCT of the chest at 6 weeks showed a total resolution of OP. This highlights the early occurrence at day 3 of RTX-OP following the first dose of RTX and the complete resolution with steroid therapy.


Subject(s)
Antineoplastic Agents , Pneumonia , B-Lymphocytes , Female , Humans , Middle Aged , Pneumonia/chemically induced , Pneumonia/drug therapy , Prednisolone , Rituximab/adverse effects , Treatment Outcome
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