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1.
Mult Scler ; 28(7): 1146-1150, 2022 06.
Article in English | MEDLINE | ID: covidwho-1861996

ABSTRACT

Monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) received emergency use authorization for the acute treatment of COVID-19. We are not aware of published data on their use in immunosuppressed people with multiple sclerosis (pwMS). We report 23 pwMS (mean age = 49 years, ocrelizumab (n = 19), fingolimod (n = 2), vaccinated with at least an initial series (n = 19)) who received mAb for acute COVID-19. Following mAb receipt, approximately half recovered in <7 days (48%). There were no adverse events or deaths. Use of mAb for pwMS treated with fingolimod or ocrelizumab was not observed to be harmful and is likely helpful for treatment of acute COVID-19.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , Fingolimod Hydrochloride/therapeutic use , Humans , Middle Aged , Multiple Sclerosis/chemically induced , Multiple Sclerosis/complications , Multiple Sclerosis/drug therapy , SARS-CoV-2
2.
Mult Scler ; 28(7): 1138-1145, 2022 06.
Article in English | MEDLINE | ID: covidwho-1861995

ABSTRACT

BACKGROUND: The effect of disease-modifying therapies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response is unclear. OBJECTIVES: We aim to determine the immunological responses to SARS-CoV-2 in multiple sclerosis (MS) and anti-CD20-treated patients with other autoimmune diseases (AID). METHODS: Humoral and cellular responses we determined before and 30-90 days after vaccination in patients with MS and anti-CD20-treated patients with other AID in two Catalan centers. RESULTS: 457 patients were enrolled. Findings showed that humoral response decreased under anti-CD20s or sphingosine 1-phosphate receptor modulators (S1PRM) and with longer treatment duration and increased after 4.5 months from the last anti-CD20 infusion. Cellular response decreased in S1PRM-treated. Patients on anti-CD20 can present cellular responses even in the absence of antibodies. CONCLUSION: Anti-CD20s and S1PRM modify the immunological responses to SARS-CoV-2 vaccines.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Multiple Sclerosis/drug therapy , SARS-CoV-2 , Vaccination
3.
Mult Scler ; 28(7): 1131-1137, 2022 06.
Article in English | MEDLINE | ID: covidwho-1861993

ABSTRACT

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.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunity , Immunoglobulin G , Multiple Sclerosis/drug therapy , SARS-CoV-2 , Technology , Vaccination , Vaccines, Synthetic
4.
Mult Scler ; 28(7): 1155-1159, 2022 06.
Article in English | MEDLINE | ID: covidwho-1861991

ABSTRACT

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.


Subject(s)
COVID-19 , Multiple Sclerosis , Neuromyelitis Optica , /administration & dosage , COVID-19/diagnosis , Fingolimod Hydrochloride/therapeutic use , Humans , Multiple Sclerosis/complications , Neuromyelitis Optica/complications , SARS-CoV-2
5.
BMC Neurol ; 22(1): 185, 2022 May 18.
Article in English | MEDLINE | ID: covidwho-1854778

ABSTRACT

BACKGROUND: Since the beginning of the COVID-19 pandemic and development of new vaccines, the issue of post-vaccination exacerbation or manifestation of demyelinating central nervous system (CNS) disorders has gained increasing attention. CASE PRESENTATION: We present a case of a 68-year-old woman previously diagnosed with multiple sclerosis (MS) since the 1980s who suffered a rapidly progressive severe sensorimotor paraparesis with loss of bladder and bowel control due to an acute longitudinal extensive transverse myelitis (LETM) after immunization with the mRNA Pfizer-BioNTech COVID-19 vaccine. Detection of Aquaporin-4-antibodies (AQP4) in both serum and CSF led to diagnosis of AQP4-antibody positive neuromyelitis optica spectrum disorder (NMOSD). Treatment with intravenous corticosteroids and plasmapheresis led to a slight improvement of the patient's symptoms. CONCLUSIONS: Pathogenic mechanisms of post-vaccination occurrence of NMOSD are still unknown. However, cases like this should make aware of rare neurological disorders manifesting after vaccination and potentially contribute to improvement of management of vaccinating patients with inflammatory CNS disorders in the future. So far two cases of AQP4-antibody positive NMOSD have been reported in association with viral vector COVID-19 vaccines. To our knowledge, we report the first case of AQP4-antibody positive NMOSD after immunization with an mRNA COVID-19-vaccine.


Subject(s)
COVID-19 , Multiple Sclerosis , Myelitis, Transverse , Neuromyelitis Optica , Aged , Aquaporin 4/blood , Aquaporin 4/cerebrospinal fluid , Autoantibodies/blood , Autoantibodies/cerebrospinal fluid , /therapeutic use , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/therapeutic use , Disease Progression , Female , Humans , Multiple Sclerosis/blood , Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/complications , Myelitis, Transverse/chemically induced , Myelitis, Transverse/diagnosis , Myelitis, Transverse/etiology , Neuromyelitis Optica/blood , Neuromyelitis Optica/cerebrospinal fluid , Neuromyelitis Optica/diagnosis , Neuromyelitis Optica/etiology , Pandemics , RNA, Messenger , Vaccination/adverse effects
6.
Mult Scler Relat Disord ; 57: 103345, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1851824

ABSTRACT

COVID-19 pandemic represented a challenge in the management of treatments for Multiple Sclerosis (MS), such as Natalizumab (NTZ). NTZ interferes with the homing of lymphocytes into the central nervous system, reducing immune surveillance against opportunistic infection. Although NTZ efficacy starts to decline 8 weeks after the last infusion, increasing the risk of disease reactivation, evidence is lacking on the safety of reinfusion during active SARS-CoV-2 infection. We report clinical outcomes of 18 pwMS receiving NTZ retreatment during confirmed SARS-CoV-2 infection. No worsening of infection or recovery delay was observed. Our data supports the safety of NTZ redosing in these circumstances.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Humans , Immunologic Factors/adverse effects , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Natalizumab/adverse effects , Pandemics , SARS-CoV-2
7.
J Neurol Sci ; 438: 120292, 2022 Jul 15.
Article in English | MEDLINE | ID: covidwho-1851604

ABSTRACT

OBJECTIVES: The present study aims to describe the evolution of teriflunomide use for multiple sclerosis (MS) in the clinical setting, in particular for naïve patients and young women. Predictors of treatment response were also investigated. METHODS: This was an independent, retrospective, real-world monocentric study. We analysed the use of teriflunomide from 2016 to 2020 in patients categorized as naïve or switchers, and assessed the variations in its use in men and women by age group. Clinical and MRI data of treated patients were evaluated, and NEDA-3 status at 24 and 36 months was defined. Determinants of therapeutic response were examined using regression analysis. RESULTS: The study included 319 MS patients exposed to teriflunomide [209 women (65.5%)]. Of these, 67 (21%) were naïve and 252 (79%) were switchers. A 20% increase of teriflunomide use in the naïve group in the past two years, particularly in 2020, the first year of global Sars-Cov-2 spread, was observed. An increase of teriflunomide use of more than 10% in young women under age 45 was also reported. NEDA-3 status was calculated for 204 patients after 24 months and was achieved in 120 (58.8%) of these ones. NEDA-3 was also achieved in 92/160 (56.8%) patients at 36 months. A lower ARR in the two years prior to teriflunomide treatment (p = 0.026), lower baseline age (p = 0.05), and lower EDSS score (p = 0.009) were associated with achievement of the NEDA-3. CONCLUSIONS: Our study confirms a major evolution in teriflunomide use in clinical settings, particularly for naïve patients and young women.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Crotonates , Female , Humans , Hydroxybutyrates , Male , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Nitriles , Retrospective Studies , SARS-CoV-2 , Toluidines
8.
J Neurol ; 269(6): 2840-2847, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1850329

ABSTRACT

BACKGROUND: Few data are available so far on the antibody-mediated immune response to anti-SARS-Cov2 vaccination in people with multiple sclerosis (pwMS) treated with disease-modifying treatments (DMTs), therefore this issue was explored in a real-life cohort of pwMS. MATERIALS AND METHODS: Retrospective monocentric study on anti-spike protein antibody response in pwMS who had received vaccination for Sars-Cov2. Adverse events following vaccination were also recorded. RESULTS: One hundred and twenty pwMS were included: 83 females (69%); median age at vaccination 42 years (range 21-73); 112/120 patients (93%) were receiving DMTs at vaccination. Anti-spike protein IgG antibodies were detectable in 102/120 (85%) cases overall, being the proportion lower in pwMS receiving anti-CD20 antibodies (14/31, 45%) compared to non-depletive treatments (77/78, 99%), p < 0.0001. Median anti-spike titre was lower in anti-CD20 antibodies and fingolimod-treated pwMS compared to those receiving other DMTs, and it correlated with anti-CD20 treatment duration (R - 0.93, p < 0.0001) and with age at vaccination in pwMS not receiving depletive treatments (R - 0.25, p = 0.028). Baseline CD19+ cell count (where available) was higher in the responder group than in non-responders, p < 0.0001. Two symptomatic COVID-19 infections were diagnosed over a median follow-up of 5 months (range 2-7); adverse events were aligned with the published literature. CONCLUSION: Antibody response to anti-COVID-19 vaccines was detected in most of the pwMS analysed, but frequency of responders was reduced in those receiving CD20 depleting therapies compared to other DMTs-treated pwMS. Investigations on cell-mediated immune response are needed to assess whether a protective immune response is elicited also in non-antibody responders.


Subject(s)
COVID-19 , Multiple Sclerosis , Adult , Aged , Antibodies, Viral , Antibody Formation , COVID-19/prevention & control , Female , Humans , Middle Aged , Multiple Sclerosis/drug therapy , RNA, Viral , Retrospective Studies , SARS-CoV-2 , Vaccination/adverse effects , Young Adult
9.
Front Immunol ; 13: 871276, 2022.
Article in English | MEDLINE | ID: covidwho-1847174

ABSTRACT

While the respiratory tract is the primary route of entry for SARS-CoV-2, evidence shows that the virus also impacts the central nervous system. Intriguingly, case reports have documented SARS-CoV-2 patients presenting with demyelinating lesions in the brain, spinal cord, and optic nerve, suggesting possible implications in neuroimmune disorders such as multiple sclerosis (MS) and other related neuroimmune disorders. However, the cellular mechanisms underpinning these observations remain poorly defined. The goal of this paper was to review the literature to date regarding possible links between SARS-CoV-2 infection and neuroimmune demyelinating diseases such as MS and its related disorders, with the aim of positing a hypothesis for disease exacerbation. The literature suggests that SARS-CoV, SARS-CoV-2, and orthologous murine coronaviruses invade the CNS via the olfactory bulb, spreading to connected structures via retrograde transport. We hypothesize that a glial inflammatory response may contribute to damaged oligodendrocytes and blood brain barrier (BBB) breakdown, allowing a second route for CNS invasion and lymphocyte infiltration. Potential for molecular mimicry and the stimulation of autoreactive T cells against myelin is also described. It is imperative that further studies on SARS-CoV-2 neuroinvasion address the adverse effects of the virus on myelin and exacerbation of MS symptoms, as nearly 3 million people suffer from MS worldwide.


Subject(s)
COVID-19 , Multiple Sclerosis , Animals , Central Nervous System , Disease Progression , Humans , Mice , Multiple Sclerosis/etiology , SARS-CoV-2
10.
Mult Scler ; 28(7): 1041-1050, 2022 06.
Article in English | MEDLINE | ID: covidwho-1846718

ABSTRACT

BACKGROUND: Optimal management of anti-CD20-treated patients with multiple sclerosis (pwMS) is an important clinical task during the current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. OBJECTIVES: To characterize humoral and cellular immune responses to SARS-CoV-2 vaccinations/infections in a longitudinal cohort of anti-CD20 treated (n = 175) and anti-CD20 therapy-naïve (n = 41) pwMS. METHODS: Anti-SARS-CoV-2 spike protein immunoglobulin G (IgG) and IgA, virus neutralizing capacity, IgG avidity and SARS-CoV-2-specific T cells were determined. RESULTS: Following two SARS-CoV-2 vaccinations, not only SARS-CoV-2 spike protein IgG and IgA, but also neutralizing capacity and avidity of SARS-CoV-2 IgG were lower in anti-CD20-treated (n = 51) than in anti-CD20 therapy-naïve pwMS (n = 14) and in healthy controls (HC, n = 19). However, in all anti-CD20-treated pwMS vaccinated twice (n = 26) or infected with SARS-CoV-2 (n = 2), in whom SARS-CoV-2-specific T cells were measured, SARS-CoV-2-specific T cells were detectable, at levels similar to those of twice-vaccinated anti-CD20 therapy-naïve pwMS (n = 7) and HC (n = 19). SARS-CoV-2-S1 IgG levels (r = 0.42, p = 0.002), antibody avidity (r = 0.7, p < 0.001), and neutralizing capacity (r = 0.44, p = 0.03) increased with time between anti-CD20 infusion and second vaccination. Based on detection of SARS-CoV-2 antibodies, SARS-CoV-2 infections occurred in 4 out of 175 (2.3%) anti-CD20-treated pwMS, all of whom recovered fully. CONCLUSIONS: These findings should inform treatment decisions and SARS-CoV-2 vaccination management in pwMS.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , COVID-19 Vaccines , Humans , Immunoglobulin A , Immunoglobulin G/therapeutic use , Multiple Sclerosis/drug therapy , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , T-Lymphocytes , Vaccination
11.
JAMA Netw Open ; 5(5): e2211497, 2022 May 02.
Article in English | MEDLINE | ID: covidwho-1838112

ABSTRACT

Importance: B-cell-depleting monoclonal antibodies are widely used for treatment of multiple sclerosis but are associated with an impaired response to vaccines. Objective: To identify factors associated with a favorable vaccine response to tozinameran. Design, Setting, and Participants: This prospective cohort study was conducted in a specialized multiple sclerosis clinic at a university hospital from January 21 to December 1, 2021. Of 75 patients evaluated for participation who received a diagnosis of multiple sclerosis with planned or ongoing treatment with rituximab, 69 were included in the study, and data from 67 were analyzed. Exposures: Sex, age, number of previous rituximab infusions, accumulated dose of rituximab, previous COVID-19 infection, time since last rituximab treatment, CD19+ B-cell count before vaccination, CD4+ T-cell count, and CD8+ T-cell count were considered potential factors associated with the main outcome. Main Outcomes and Measures: Serological vaccine responses were measured by quantitation of anti-spike immunoglobulin G (IgG) antibodies, anti-receptor-binding domain (RBD) IgG antibodies, and their neutralizing capacities. Cellular responses to spike protein-derived SARS-CoV-2 peptide pools were assessed by counting interferon gamma spot-forming units in a FluoroSpot assay. Results: Among 60 patients with ongoing rituximab treatment (49 women [82%]; mean (SD) age, 43 [10] years), the median (range) disease duration was 9 (1-29) years, and the median (range) dose of rituximab was 2750 (500-10 000) mg during a median (range) time of 2.8 (0.5-8.3) years. The median (range) follow-up from the first vaccination dose was 7.3 (4.3-10.0) months. Vaccine responses were determined before vaccination with tozinameran and 6 weeks after vaccination. By using established cutoff values for anti-spike IgG (264 binding antibody units/mL) and anti-RBD IgG (506 binding antibody units/mL), the proportion of patients with a positive response increased with the number of B cells, which was the only factor associated with these outcomes. A cutoff for the B-cell count of at least 40/µL was associated with an optimal serological response. At this cutoff, 26 of 29 patients (90%) had positive test results for anti-spike IgG and 21 of 29 patients (72%) for anti-RBD IgG, and 27 of 29 patients (93%) developed antibodies with greater than 90% inhibition of angiotensin-converting enzyme 2. No factor associated with the cellular response was identified. Depending on the peptide pool, 21 of 25 patients (84%) to 22 of 25 patients (88%) developed a T-cell response with interferon gamma production at the B-cell count cutoff of at least 40/µL. Conclusions and Relevance: This cohort study found that for an optimal vaccine response from tozinameran, rituximab-treated patients with multiple sclerosis may be vaccinated as soon as possible, with rituximab treatment delayed until B-cell counts have reached at least 40/µL. An additional vaccination with tozinameran should be considered at that point.


Subject(s)
COVID-19 , Multiple Sclerosis , Adult , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Cohort Studies , Female , Humans , Immunoglobulin G , Interferon-gamma , Male , Multiple Sclerosis/drug therapy , Prospective Studies , Rituximab/therapeutic use , SARS-CoV-2 , Vaccination
12.
Indian J Ophthalmol ; 70(5): 1833-1836, 2022 05.
Article in English | MEDLINE | ID: covidwho-1835132

ABSTRACT

Multiple sclerosis and neuromyelitis optica spectrum disorder may be seen in the acute setting of coronavirus disease 2019 (COVID-19) infection or even post-recovery. Such patients may present with optic neuropathy along with weakness in the back and lower limbs. Ascending paralysis can present with respiratory distress in acute COVID-19 infection and may even prove to be fatal. We report a unique case of a 16-year-old female with past history of COVID-19 infection having optic neuropathy, and radioimaging showing demyelinating plaques in the central nervous system with spinal cord edema. Serology showed positivity for rheumatoid arthritis, and the patient was managed with steroids and rituximab.


Subject(s)
COVID-19 , Multiple Sclerosis , Neuromyelitis Optica , Adolescent , COVID-19/complications , Female , Humans , Neuromyelitis Optica/complications , Neuromyelitis Optica/diagnosis , Optic Nerve , Rituximab
13.
Neurol Neuroimmunol Neuroinflamm ; 9(4)2022 Jul.
Article in English | MEDLINE | ID: covidwho-1833441

ABSTRACT

OBJECTIVES: To evaluate whether a third vaccination shows an added effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T-cell responses in patients with multiple sclerosis treated with ocrelizumab or fingolimod. METHODS: This is a substudy of a prospective multicenter study on SARS-CoV-2 vaccination in patients with immune-mediated diseases. Patients with MS treated with ocrelizumab, fingolimod, and no disease-modifying therapies and healthy controls were included. The number of interferon (IFN)-γ secreting SARS-CoV-2-specific T cells at multiple time points before and after 3 SARS-CoV-2 vaccinations were evaluated. RESULTS: In ocrelizumab-treated patients (N = 24), IFN-γ-producing SARS-CoV-2-specific T-cell responses were induced after 2 vaccinations with median levels comparable to healthy controls (N = 12) and patients with MS without disease-modifying therapies (N = 10). A third vaccination in ocrelizumab-treated patients (N = 8) boosted T-cell responses that had declined after the second vaccination, but did not lead to higher overall T-cell responses as compared to immediately after a second vaccination. In fingolimod-treated patients, no SARS-CoV-2-specific T cells were detected after second (N = 12) and third (N = 9) vaccinations. DISCUSSION: In ocrelizumab-treated patients with MS, a third SARS-CoV-2 vaccination had no additive effect on the maximal T-cell response but did induce a boost response. In fingolimod-treated patients, no T-cell responses could be detected following both a second and third SARS-CoV-2 vaccination.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunity, Cellular , Multiple Sclerosis , T-Lymphocytes , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Fingolimod Hydrochloride/therapeutic use , Humans , Immunization, Secondary , Interferon-gamma , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Prospective Studies , SARS-CoV-2 , T-Lymphocytes/immunology , Vaccination
14.
BMC Neurol ; 22(1): 144, 2022 Apr 18.
Article in English | MEDLINE | ID: covidwho-1808348

ABSTRACT

BACKGROUND: As a chronic, disabling disease, multiple sclerosis (MS) has challenged healthcare systems in many ways. MS adversely affects patients' quality of life and self-efficacy and results in psychological stress. The present study was conducted to investigate the effect of peer education based on Pender's health promotion model on the quality of life, stress management, and self-efficacy of patients with MS in the south of Iran. METHODS: The present study was a randomized controlled clinical trial. A total of 90 patients were divided into group A intervention group 45 patients) and group B (control group 45 patients). The intervention was peer education based on Pender's health promotion model. Data were collected using the MS Quality of Life Scale, the Self-efficacy Scale, and the Stress Management Scale. Data analyses were conducted using SPSS version 22. To analyze the data, we used descriptive statistics. Thus, inferential statistics applied included Chi-square, independent-samples t-test, and Repeated measures (ANOVA). The significance level was considered p < 0.05. RESULTS: The quality of life, self-efficacy, and stress management mean scores of the intervention group as measured immediately and 3 months after intervention were significant (p < 0.05). As for the control group, however, the difference was not significant. CONCLUSION: Peer education based on Pender's health promotion model improves patients' quality of life, stress management, and self-efficacy with multiple sclerosis. Nursing managers and health system policymakers can use this educational approach for patients with other chronic diseases to enhance their quality of life and self-efficacy. TRIAL REGISTRATION: Iranian Registry of Clinical Trials: IRCT registration number: IRCT20190917044802N3 .


Subject(s)
Multiple Sclerosis , Quality of Life , Health Promotion , Humans , Iran/epidemiology , Multiple Sclerosis/therapy , Self Efficacy
16.
J Neurol ; 269(5): 2286-2292, 2022 May.
Article in English | MEDLINE | ID: covidwho-1802708

ABSTRACT

BACKGROUND: The majority of multiple sclerosis [MS] patients treated with fingolimod fail to develop a protective level of IgG humoral and adaptive cellular immune responses following full BNT162b2 SARS-CoV-2 vaccination. OBJECTIVE: To compare the efficacy of the third COVID-19 vaccine dose in vaccine non-responders fingolimod-treated MS patients. STUDY DESIGN: This is a prospective 3-month, single-center, randomized clinical trial. METHODS: Twenty relapsing MS patients who had been on fingolimod therapy ≥ 12 months and failed to develop humoral IgG immune response to 2-dose Pfizer BNT162b2 COVID-19 vaccination were randomized into two groups: fingolimod-continuation group and fingolimod-discontinuation group. Humoral and memory cellular immune responses were assessed within 1 and 3 months following the third Pfizer BNT162b2 vaccine dose and compared between the groups. RESULTS: A higher rate of patients in the fingolimod-discontinuation group [n = 8/10] compared to fingolimod-continuation group [n = 2/10] developed positive SARS-COV-2 IgG. Median IgG titer 1 month following the third dose was 202.3 BAU/ml vs. 26.4 BAU/ml, respectively, p = 0.022. The development of IgG humoral response correlated with absolute lymphocyte count. Specific SARS-COV-2 memory B cell and T cell immune responses were not detected in both groups, either at 1 month or 3 months following the third COVID-19 vaccine dose. CONCLUSIONS: Short period of fingolimod treatment discontinuation was associated with the development of humoral protection but not with adaptive cellular immunity.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Fingolimod Hydrochloride/therapeutic use , Humans , Immunity , Immunoglobulin G , Lymphocyte Count , Multiple Sclerosis/drug therapy , Prospective Studies , SARS-CoV-2
18.
Front Immunol ; 13: 868915, 2022.
Article in English | MEDLINE | ID: covidwho-1793012

ABSTRACT

Background: Immunomodulatory/immunosuppressive activity of multiple sclerosis (MS) disease modifying therapies (DMTs) might affect immune responses to SARS-CoV-2 exposure or vaccination in patients with MS (PwMS). We evaluated the effect of DMTs on humoral and cell-mediated immune responses to 2 and 3 vaccinations and the longevity of SARS-Cov-2 IgG levels in PwMS. Methods: 522 PwMS and 68 healthy controls vaccinated with BNT162b2-Pfizer mRNA vaccine against SARS-CoV-2, or recovering from COVID-19, were recruited in a nation-wide multi-center study. Blood was collected at 3 time-points: 2-16 weeks and ~6 months post 2nd vaccination and 1-16 weeks following 3rd vaccination. Serological responses were measured by quantifying IgG levels against the spike-receptor-binding-domain of SARS-CoV-2, and cellular responses (in a subgroup analysis) by quantifying IFNγ secretion in blood incubated with COVID-19 spike-antigen. Results: 75% PwMS were seropositive post 2nd or 3rd vaccination. IgG levels decreased by 82% within 6 months from vaccination (p<0.0001), but were boosted 10.3 fold by the 3rd vaccination (p<0.0001), and 1.8 fold compared to ≤3m post 2nd vaccination (p=0.025). Patients treated with most DMTs were seropositive post 2nd and 3rd vaccinations, however only 38% and 44% of ocrelizumab-treated patients and 54% and 46% of fingolimod-treated patients, respectively, were seropositive. Similarly, in COVID-19-recovered patients only 54% of ocrelizumab-treated, 75% of fingolimod-treated and 67% of cladribine-treated patients were seropositive. A time interval of ≥5 months between ocrelizumab infusion and vaccination was associated with higher IgG levels (p=0.039 post-2nd vaccination; p=0.036 post-3rd vaccination), and with higher proportions of seropositive patients. Most fingolimod- and ocrelizumab-treated patients responded similarly to 2nd and 3rd vaccination. IFNγ-T-cell responses were detected in 89% and 63% of PwMS post 2nd and 3rd vaccination, however in only 25% and 0% of fingolimod-treated patients, while in 100% and 86% of ocrelizumab-treated patients, respectively. Conclusion: PwMS treated with most DMTs developed humoral and T-cell responses following 2 and 3 mRNA SARS-CoV-2 vaccinations. Fingolimod- or ocrelizumab-treated patients had diminished humoral responses, and fingolimod compromised the cellular responses, with no improvement after a 3rd booster. Vaccination following >5 months since ocrelizumab infusion was associated with better sero-positivity. These findings may contribute to the development of treatment-stratified vaccination guidelines for PwMS.


Subject(s)
COVID-19 , Multiple Sclerosis , COVID-19/prevention & control , COVID-19 Vaccines , Fingolimod Hydrochloride/therapeutic use , Humans , Immunity, Cellular , Immunoglobulin G/therapeutic use , Israel , Multiple Sclerosis/drug therapy , RNA, Messenger/therapeutic use , SARS-CoV-2 , Vaccination , Vaccines, Synthetic
20.
Expert Rev Clin Immunol ; 18(5): 495-512, 2022 May.
Article in English | MEDLINE | ID: covidwho-1784113

ABSTRACT

INTRODUCTION: SARS-CoV-2 pandemic has led the scientific community to maximize efforts to prevent infections and disease severity in patients with multiple sclerosis (pwMS). We analyze the impact of immunotherapies on COVID-19 outcomes in pwMS, providing our interpretation of data. AREAS COVERED: Infections, hospitalizations, intensive care unit admissions, and death rates in COVID-19 pwMS are comparable to the general population. Severity of disability, MS clinical phenotype, age, and comorbidities, along with the use of intravenous methylprednisolone and anti-CD20 treatments, are risk factors for COVID-19 severity. Disease-modifying treatments (DMTs) can be safely started and continued during the pandemic. Benefit-risk evaluation is mandatory when managing second-line therapies to balance risk of worse COVID-19 outcomes and MS reactivation. COVID-19 vaccination is safe in MS, and its efficacy could be reduced in fingolimod- and ocrelizumab-treated patients. EXPERT OPINION: The rate of (re)-infection and outcomes with SARS-CoV-2 variants in pwMS and antiviral properties of DMTs need to be further explored. Data on COVID-19 in pregnant MS women, children, and elderly pwMS are limited. Evidence on long-term effects of infection is needed. Impact of emerging DMTs on COVID-19 should be investigated. More data and longer follow-up are needed to characterize long-term efficacy and safety profile of vaccinations in pwMS.


Subject(s)
COVID-19 , Multiple Sclerosis , Aged , COVID-19 Vaccines , Female , Humans , Multiple Sclerosis/drug therapy , SARS-CoV-2 , Vaccination
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