scholarly journals Post-vaccine COVID-19 in patients with multiple sclerosis or neuromyelitis optica

2021 ◽  
pp. 135245852110497
Author(s):  
Edouard Januel ◽  
Jérôme De Seze ◽  
Patrick Vermersch ◽  
Elisabeth Maillart ◽  
Bertrand Bourre ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Immunoglobulin G ◽  
Vaccine Efficacy ◽  
Case Series ◽  
Vaccine Dose ◽  
Spike Protein ◽  
Biological Study ◽  
Anti Cd20

Introduction: Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry. Case series: We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild. Discussion: These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.

scholarly journals Efficacy and safety of a third SARS-CoV-2 vaccination in multiple sclerosis vaccine non-responders

2021 ◽  
Author(s):  
Marton Konig ◽  
Hilde Marie Torgauten ◽  
Marthias Herstad Overas ◽  
Adity Chopra ◽  
Aslaug Rudjord Lorentzen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Side Effects ◽  
Severe Acute Respiratory Syndrome ◽  
Humoral Immunity ◽  
Vaccine Dose ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Efficacy And Safety ◽  
Immunization Registry ◽  
Anti Cd20

Importance: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to protect against coronavirus disease of 2019 (COVID-19) is recommended for patients with multiple sclerosis (pwMS). However, approximately 80% of all pwMS treated with anti-CD20 therapy (rituximab, ocrelizumab) or fingolimod have low or absent humoral immunity after vaccination with two doses of SARS-CoV-2 mRNA vaccines. The efficacy and safety of a third vaccine dose in this group is largely unknown. Objective: To characterize the humoral immunogenicity and the safety of a third dose of mRNA-COVID-19 vaccine in anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity (i.e., anti-SARS-CoV-2 IgG <70 arbitrary units (AU) and <5 AU, respectively) after two vaccinations. Design, setting and participants: 130 anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity despite full vaccination against SARS-CoV-2, received a third dose of SARS-CoV-2 mRNA vaccine. Humoral immunity (i.e., antibody response against SARS-CoV-2) and the frequency and characteristics of side-effects were analyzed in all participants. Exposures: A third vaccine dose against SARS-CoV-2 with BNT162b2- or mRNA-1273-COVID-19 vaccine. Main outcomes and measures: Patient- and treatment-specific variables were acquired using a digital questionnaire, the Norwegian Immunization Registry and hospital journals. Humoral immunity was assessed by measuring SARS-CoV-2 SPIKE receptor-binding domain (RBD) IgG response. Low/absent humoral immunity was assumed in cases of AU<70 after anti-SPIKE protein-based serology 3-5 weeks after revaccination. Results: A third dose of SARS-CoV-2 mRNA vaccine increased anti-SARS-CoV-2 SPIKE RBD IgG levels significantly. The proportion of patients with assumed protective humoral immunity (anti-SARS-CoV-2 SPIKE RBD IgG > 70 AU) were 25% among patients using anti-CD20 therapy and 7% among those treated with fingolimod. No adverse events were registered during the study period. Conclusion and relevance: A third dose of mRNA-COVID-19 vaccine was associated with significantly increased levels of anti-SARS-CoV-2 SPIKE RBD IgG, and hence assumed protective humoral immunity - in anti-CD20- or fingolimod-treated pwMS with low or absent humoral immunity despite full vaccination. The effect of a third vaccine dose was limited and more prominent among those treated with anti-CD20 therapy.

scholarly journals Anti-CD20 therapies decrease humoral immune response to SARS-CoV-2 in patients with multiple sclerosis or neuromyelitis optica spectrum disorders

2021 ◽  
pp. jnnp-2021-326904
Author(s):  
Céline Louapre ◽  
Michella Ibrahim ◽  
Elisabeth Maillart ◽  
Basma Abdi ◽  
Caroline Papeix ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Seroconversion Rate ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Linear Regression Models ◽  
Positive Serology ◽  
Humoral Immune ◽  
Antibody Positivity ◽  
Spectrum Disorders ◽  
Anti Cd20

BackgroundSARS-CoV-2 seroconversion rate after COVID-19 may be influenced by disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMO-SD).ObjectiveTo investigate the seroprevalence and the quantity of SARS-CoV-2 antibodies in a cohort of patients with MS or NMO-SD.MethodsBlood samples were collected in patients diagnosed with COVID-19 between 19 February 2020 and 26 February 2021. SARS-CoV-2 antibody positivity rates and Ig levels (anti-S IgG titre, anti-S IgA index, anti-N IgG index) were compared between DMTs groups. Multivariate logistic and linear regression models were used to estimate the influence of DMTs and other confounding variables on SARS-CoV-2 serological outcomes.Results119 patients (115 MS, 4 NMO, mean age: 43.0 years) were analysed. Overall, seroconversion rate was 80.6% within 5.0 (SD 3.4) months after infection. 20/21 (95.2%) patients without DMT and 66/77 (85.7%) patients on DMTs other than anti-CD20 had at least one SARS-CoV-2 Ig positivity, while this rate decreased to only 10/21 (47.6%) for patients on anti-CD20 (p<0.001). Being on anti-CD20 was associated with a decreased odd of positive serology (OR, 0.07 (95% CI 0.01 to 0.69), p=0.02) independently from time to COVID-19, total IgG level, age, sex and COVID-19 severity. Time between last anti-CD20 infusion and COVID-19 was longer (mean (SD), 3.7 (2.0) months) in seropositive patients compared with seronegative patients (mean (SD), 1.9 (1.5) months, p=0.04).ConclusionsSARS-CoV-2 antibody response was decreased in patients with MS or NMO-SD treated with anti-CD20 therapies. Monitoring long-term risk of reinfection and specific vaccination strategies in this population may be warranted.Trial registration numberNCT04568707.

scholarly journals Anti-CD20 and COVID-19 in multiple sclerosis and related disorders: A case series of 60 patients from Madrid, Spain

2020 ◽  
Vol 42 ◽  
pp. 102185 ◽  
Author(s):  
Paloma Montero-Escribano ◽  
Jorge Matías-Guiu ◽  
Patricia Gómez-Iglesias ◽  
Jesús Porta-Etessam ◽  
Vanesa Pytel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Case Series ◽  
Anti Cd20

A Girl With Back Pain, Paresthesias, and Painful Vision Loss

2021 ◽  
pp. 44-47
Author(s):  
Cecilia Zivelonghi ◽  
Andrew McKeon
Keyword(s):  
Back Pain ◽  
Neuromyelitis Optica ◽  
Immunoglobulin G ◽  
Vision Loss ◽  
Spectrum Disorder ◽  
Aquaporin 4 ◽  
Lower Limbs ◽  
First Episode ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Anti Cd20

A 12-year-old girl sought care for subacute onset of cramping back pain, along with paresthesias in her lower limbs up to the waistline, both hands, upper back, and chest, followed by rapidly progressive (over a few hours) painful vision loss affecting initially the right eye with subsequent involvement of the left eye. She underwent neuroophthalmologic evaluation and was diagnosed with bilateral optic neuritis. A positive Lhermitte sign was also present. The patient was tested for aquaporin-4-immunoglobulin G autoantibodies, which were positive in both serum and cerebrospinal fluid. A diagnosis of aquaporin-4-immunoglobulin G–positive neuromyelitis optica was made. The patient was treated with rituximab (anti-CD20 monoclonal antibody) and became episode-free, with no further accumulation of disability. The discovery of aquaporin-4-immunoglobulin G in 2004 has permitted the distinction of neuromyelitis optica spectrum disorder from other inflammatory central nervous system disorders. Aquaporin-4-immunoglobulin G represents a highly specific biomarker for neuromyelitis optica (almost 100% using molecular-based techniques), with sensitivity of approximately 80%. According to the most recent diagnostic criteria published in 2015, a diagnosis of neuromyelitis optica spectrum disorder can also be made for patients who are aquaporin-4-immunoglobulin G seronegative by any testing method, regardless of assay sensitivity, provided that more stringent clinical and radiologic requirements are met. Serial testing is recommended for these patients because late seroconversion has been described up to 4 years after the first episode.

scholarly journals IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel

2005 ◽  
Vol 202 (4) ◽  
pp. 473-477 ◽  
Author(s):  
Vanda A. Lennon ◽  
Thomas J. Kryzer ◽  
Sean J. Pittock ◽  
A.S. Verkman ◽  
Shannon R. Hinson
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Blood Brain Barrier ◽  
Neuromyelitis Optica ◽  
Immunoglobulin G ◽  
Protein Complex ◽  
Demyelinating Disease ◽  
Water Channel ◽  
Aquaporin 4 ◽  
Specific Marker

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serves as a specific marker for NMO. Here we show that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. NMO may represent the first example of a novel class of autoimmune channelopathy.

scholarly journals Incidence and Predictive Risk Factors of Infective Events in Patients With Multiple Sclerosis Treated With Agents Targeting CD20 and CD52 Surface Antigens

2019 ◽  
Vol 6 (11) ◽  
Author(s):  
Emanuela Zappulo ◽  
Antonio Riccardo Buonomo ◽  
Francesco Saccà ◽  
Cinzia Valeria Russo ◽  
Riccardo Scotto ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Opportunistic Infections ◽  
Case Series ◽  
Prior Exposure ◽  
Cytomegalovirus Reactivation ◽  
Immune Impairment ◽  
Predictive Risk ◽  
Anti Cd20

Abstract Objective Monoclonal antibodies (MAbs) directed against the CD20 and CD52 antigens are used increasingly in patients with multiple sclerosis (MS). Several life-threatening opportunistic infections have been reported in postmarketing case series. The aim of this study was to investigate the incidence of infections and associated prognostic factors during the first year of treatment in patients receiving anti-CD20 (ocrelizumab or rituximab) or anti-CD52 MAbs (alemtuzumab). Methods A retrospective study was conducted in patients with MS referring to the Neurodegenerative Diseases Center at the University of Naples Federico II who received MAbs between November 2015 and June 2018. Results A total of 163 patients were enrolled. Approximately 40% of patients experienced lymphocytopenia during treatment. Eighty-six infective events were reported in 67 patients (41%). Bacterial infections were significantly more frequent with anti-CD20, whereas viral infections prevailed with alemtuzumab. Cytomegalovirus reactivation rates were significantly higher in the alemtuzumab group than in patients on anti-CD20 (51% vs 6%, P < .001). The overall annualized infection rate was 1.1 per patient-year, higher in patients on anti-CD52 versus those on anti-CD20 regimens (1.5 vs 0.8 per patient-year). Alemtuzumab treatment, prior exposure to ≥2 MS drugs, and iatrogenic immune impairment significantly and independently predicted an infection event (adjusted hazard ratio [aHR], 2.7; P = .013; aHR, 1.7; P = .052; and aHR, 2.9; P = .004; respectively). Conclusions Given their considerable infection risk, MS patients receiving MAbs should undergo timely follow up and tailored preventive interventions. Anti-CD52–based treatment, prior exposure to MS drugs, and on-treatment immune impairment are significant predictive factors of infection and their evaluation could help clinicians to stratify a patient’s risk of infection.

scholarly journals A cohort of 222 anti-CD20 treated patients with multiple sclerosis followed through the COVID-19 pandemic: Attenuated humoral but robust cellular immune responses after vaccination and infection

2021 ◽  
Author(s):  
Tatjana Schwarz ◽  
Carolin Otto ◽  
Terry C Jones ◽  
Florence Pache ◽  
Patrick Schindler ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Immune Responses ◽  
Detection Rate ◽  
Spike Protein ◽  
Antibody Avidity ◽  
Cellular Immune Responses ◽  
Neutralizing Capacity ◽  
Anti Cd20 ◽  
Cellular Immune

Importance: Data on immune responses following SARS-CoV-2 vaccinations/infections and on detection rate of SARS-CoV-2 infections in anti-CD20 treated patients with multiple sclerosis (pwMS) are important for guiding management of pwMS during the current SARS-CoV-2 pandemic. Objective: To analyze humoral and cellular immune responses to SARS-CoV-2 vaccinations/infections and to determine the detection rate of SARS-CoV-2 infections in anti-CD20 treated pwMS. Design: Prospective single-center cohort study from March 2020 to August 2021. Setting: MS referral center, Charite - Universitaetsmedizin Berlin, Germany. Participants: 222 consecutive pwMS (128 [57.7%] female, median [range] age 39 [17-81] years). 181 patients were on anti-CD20 therapy at study inclusion, 41 began anti-CD20 therapy during the study. Hospital employees (HE, n=19) served as controls. Exposures: pwMS were exposed to anti-CD20 therapy for 169.5 patient years. 51 patients under anti-CD20 treatment, 14 patients before anti-CD20 treatment, and 19 HE were vaccinated twice against SARS-CoV-2. Main outcomes: SARS-CoV-2 spike protein immunoglobulin (Ig)G (ELISA and immunofluorescence), IgA (ELISA), IgG to four recombinant SARS-CoV-2 antigens (solid phase immunoassay), neutralizing capacity of SARS-CoV-2 antibodies (plaque reduction neutralization test), SARS-CoV-2 IgG avidity (modified ELISA), and SARS-CoV-2 specific T cells (interferon-γ release assay). Results: Following two SARS-CoV-2 vaccinations, median (IQR) levels of SARS-CoV-2 spike protein IgG (OD ratio: 1.2 [0.1-5.1] vs. 9.0 [6.8-9.9] vs. 8.8 [8.0-9.4], p<0.0001), neutralizing capacity (PRNT50 Titer: 40 [0-80] vs. 640 [80-640] vs. 640 [320-640], p≤0.006), and antibody avidity (43.6% [14.8-54.6%] vs. 84.1% [53.1-86.8%] vs. 89.7 [76.8-93.4%], p≤0.003) were lower in anti-CD20 treated pwMS than in pwMS before initiation of anti-CD20 therapy and in HE. All anti-CD20 treated pwMS vaccinated twice developed SARS-CoV-2 specific T cells, whose levels did not differ from those of pwMS before initiation of anti-CD20 therapy and HE. SARS-CoV-2 IgG levels (r=0.42, p=0.002) and antibody avidity (r=0.70, p<0.001) increased with time between anti-CD20 infusion and second vaccination. The detection rate of SARS-CoV-2 infections in anti-CD20 treated pwMS (2.36/100 patient years) was similar to that of RT-PCR confirmed SARS-CoV-2 cases in the general Berlin population (3.75/100 person years) during the study period. Interpretation: These findings are relevant for treatment decisions as well as management of SARS-CoV-2 vaccinations in pwMS.

scholarly journals Immunoglobulin G immune response to SARS-CoV-2 vaccination in people living with multiple sclerosis within Multiple Sclerosis Partners Advancing Technology and Health Solutions

2022 ◽  
pp. 135245852110613
Author(s):  
Jeffrey A Cohen ◽  
Robert A Bermel ◽  
Cynthia I Grossman ◽  
Carrie M Hersh ◽  
Megan Hyland ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immunoglobulin G ◽  
Post Vaccination ◽  
Vaccination Response ◽  
Disease Modifying Therapies ◽  
Igg Index ◽  
Sphingosine 1 Phosphate ◽  
Anti Cd20 ◽  
The Impact ◽  
Receptor Modulators

Background: The impact of multiple sclerosis (MS) disease-modifying therapies (DMTs) on SARS-CoV-2 vaccination response is uncertain. Methods: Post-SARS-CoV-2 vaccination blood samples across multiple DMTs were tested for SARS-CoV-2 immunoglobulin G (IgG) response. Results: Three hundred twenty-two people with MS were included; 91.9% received an mRNA vaccine. Post-vaccination reactive IgG rates (IgG index > 1) were 40% for anti-CD20 (32/80 patients); 41% for sphingosine 1-phosphate receptor modulators (S1PRM, 16/39); and 100% for all other classes, including the no DMT group. Conclusion: Anti-CD20 therapies and S1PRMs reduce IgG response to SARS-CoV-2 vaccination; IgG response is preserved with other DMTs.

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