COVID-19 outcomes in persons with multiple sclerosis treated with rituximab

Iyer, Rajesh B; Raghavendra, S.; M, Javeria Nooraine; Jaychandran, R

doi:10.1016/j.msard.2021.103371

Cited by 13 publications

(12 citation statements)

References 29 publications

(21 reference statements)

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“…[3][4][5][6] In particular, aCD20-BCD therapies with rituximab and ocrelizumab and the sphingosine-1-phosphate (S1P) receptor functional antagonist fingolimod increased the risk of infection, hospitalisation and fatality. [6][7][8][9] Fortunately, vaccines against SARS-CoV-2 became available within a year after the new virus strain emerged and two mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), demonstrated strong immunogenicity, efficacy and safety in their corresponding clinical trials receiving approval at the end of 2020. 10 11 Due to their increased risk for severe COVID-19, patients with MS were prioritised for vaccination, 12 however, it was expected that their highly immunomodulatory MS treatments compromise the immunogenicity of the vaccine and alter protection.…”

Section: Introductionmentioning

confidence: 99%

“…For patients with the autoimmune disease multiple sclerosis (MS), studies have produced mixed results regarding patient susceptibility and severity of COVID-19 mainly due to differences between the treatment 3–6. In particular, aCD20-BCD therapies with rituximab and ocrelizumab and the sphingosine-1-phosphate (S1P) receptor functional antagonist fingolimod increased the risk of infection, hospitalisation and fatality 6–9. Fortunately, vaccines against SARS-CoV-2 became available within a year after the new virus strain emerged and two mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), demonstrated strong immunogenicity, efficacy and safety in their corresponding clinical trials receiving approval at the end of 2020 10 11.…”

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod

Meyer-Arndt

Braun

Fauchère

et al. 2022

J Neurol Neurosurg Psychiatry

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BackgroundSARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there are limited data on how disease-modifying therapies (DMTs) alter SARS-CoV-2 mRNA vaccine immunogenicity in patients with autoimmune diseases.MethodsAs part of a prospective cohort study, we investigated the induction, stability and boosting of vaccine-specific antibodies, B cells and T cells in patients with multiple sclerosis (MS) on different DMTs after homologous primary, secondary and booster SARS-CoV-2 mRNA vaccinations. Of 126 patients with MS analysed, 105 received either anti-CD20-based B cell depletion (aCD20-BCD), fingolimod, interferon-β, dimethyl fumarate, glatiramer acetate, teriflunomide or natalizumab, and 21 were untreated MS patients for comparison.ResultsIn contrast to all other MS patients, and even after booster, most aCD20-BCD- and fingolimod-treated patients showed no to markedly reduced anti-S1 IgG, serum neutralising activity and a lack of receptor binding domain-specific and S2-specific B cells. Patients receiving fingolimod additionally lacked spike-reactive CD4+ T cell responses. The duration of fingolimod treatment, rather than peripheral blood B and T cell counts prior to vaccination, determined whether a humoral immune response was elicited.ConclusionsThe lack of immunogenicity under long-term fingolimod treatment demonstrates that functional immune responses require not only immune cells themselves, but also access of these cells to the site of inoculation and their unimpeded movement. The absence of humoral and T cell responses suggests that fingolimod-treated patients with MS are at risk for severe SARS-CoV-2 infections despite booster vaccinations, which is highly relevant for clinical decision-making and adapted protective measures, particularly considering additional recently approved sphingosine-1-phosphate receptor antagonists for MS treatment.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod

Meyer-Arndt

Braun

Fauchère

et al. 2022

J Neurol Neurosurg Psychiatry

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“…Considered their mechanism of action, DMTs might be to some extent associated with an increased risk of infection or COVID-19 severity and mortality. [2][3][4] WHAT IS ALREADY KNOWN ON THIS TOPIC ⇒ Most of the studies have investigated the serological and/or cell-mediated response to SARS-CoV-2 vaccination focusing only on anti-CD20-treated or fingolimod-treated patients.…”

Section: Introductionmentioning

confidence: 99%

“…Most PwMS are treated with immunomodulatory or immunosuppressive disease-modifying therapies (DMTs), including interferon (IFN)-β, fingolimod, ocrelizumab and cladribine. Considered their mechanism of action, DMTs might be to some extent associated with an increased risk of infection or COVID-19 severity and mortality 2–4…”

Section: Introductionmentioning

confidence: 99%

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Longitudinal characterisation of B and T-cell immune responses after the booster dose of COVID-19 mRNA-vaccine in people with multiple sclerosis using different disease-modifying therapies

Aiello

Coppola

Ruggieri

et al. 2022

J Neurol Neurosurg Psychiatry

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BackgroundThe decline of humoral response to COVID-19 vaccine led to authorise a booster dose. Here, we characterised the kinetics of B-cell and T-cell immune responses in patients with multiple sclerosis (PwMS) after the booster dose.MethodsWe enrolled 22 PwMS and 40 healthcare workers (HCWs) after 4–6 weeks from the booster dose (T3). Thirty HCWs and 19 PwMS were also recruited 6 months (T2) after the first dose. Antibody response was measured by anti-receptor-binding domain (RBD)-IgG detection, cell-mediated response by an interferon (IFN)-γ release assay (IGRA), Th1 cytokines and T-cell memory profile by flow cytometry.ResultsBooster dose increased anti-RBD-IgG titers in fingolimod-treated, cladribine-treated and IFN-β-treated patients, but not in ocrelizumab-treated patients, although antibody titres were lower than HCWs. A higher number of fingolimod-treated patients seroconverted at T3. Differently, T-cell response evaluated by IGRA remained stable in PwMS independently of therapy. Spike-specific Th1-cytokine response was mainly CD4+T-cell-mediated, and in PwMS was significantly reduced (p<0.0001) with impaired IL-2 production compared with HCWs at T3. In PwMS, total Th1 and IFN-γ CD4+T-cell responders to spike protein were increased from T2 to T3.Compared with HCWs, PwMS presented a higher frequency of CD4+and CD8+terminally differentiated effector memory cells and of CD4+effector memory (TEM) cells, independently of the stimulus suggesting the association of this phenotype with MS status. CD4+and CD8+TEMcell frequency was further increased at T3 compared with T2.ConclusionsCOVID-19 vaccine booster strengthens humoral and Th1-cell responses and increases TEMcells in PwMS.

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Clinical characteristics and factors for serious outcomes among outpatients infected with the Omicron subvariant BF.7

Yang,

Wang,

Zhang

et al. 2023

Journal of Medical Virology

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To evaluate clinical characteristics and identify risk factors associated with severe outcomes in outpatients infected with the Omicron subvariant BF.7, data were collected from outpatients diagnosed with Corona Virus Disease 2019 from December 19, 2022 to January 5, 2023. Clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with serious outcomes. Variables with a p < 0.10 in the univariate analysis were included in the multivariate model. Our study analyzed 770 patients, of whom 380 (49.4%) were male, with a median age of 59. The most common symptoms reported were cough (71.2%), fever (64.7%), and sore throat (37.7%). Fever lasted an average of 5.93 ± 3.37 days for the general population and 10.64 ± 7.12 days for impaired‐immunity patients. Most cases were mild (68.7%), followed by moderate (27.1%). Severe cases accounted for 2.2%, with 0.5% critically ill. Serious outcomes occurred in 4.2% of cases, with 11 deaths during follow‐up. Underlying‐diseases patients had a higher rate of serious outcomes. Factors associated with serious outcomes included receiving a three‐dose vaccination (odds ratio [OR] = 0.324, 95% confidence interval [CI]: 0.113–0.932, p = 0.037), male gender (OR = 2.890, 95% CI: 1.107–7.548, p = 0.030), age (OR = 1.060, 95% CI: 1.024–1.097, p = 0.001), and chest tightness or dyspnea at the time of visit (OR = 4.861, 95% CI: 2.054–11.507, p < 0.001). Our study found that cough, fever, and sore throat were the most common symptoms reported by patients. Receiving a three‐dose vaccination was protective, while male gender, age, and chest tightness or dyspnea were identified as risk factors for serious outcomes.

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COVID-19 outcomes in persons with multiple sclerosis treated with rituximab

Cited by 13 publications

References 29 publications

SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod

SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod

Longitudinal characterisation of B and T-cell immune responses after the booster dose of COVID-19 mRNA-vaccine in people with multiple sclerosis using different disease-modifying therapies

Clinical characteristics and factors for serious outcomes among outpatients infected with the Omicron subvariant BF.7

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