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2.
J Immunol ; 208(7): 1519-1524, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1742798

ABSTRACT

Multiple sclerosis (MS) is a demyelinating inflammatory disease of the CNS treated by diverse disease-modifying therapies that suppress the immune system. Severe acute respiratory syndrome coronavirus 2 mRNA vaccines have been very effective in immunocompetent individuals, but whether MS patients treated with modifying therapies are afforded the same protection is not known. This study determined that dimethyl fumarate caused a momentary reduction in anti-Spike (S)-specific Abs and CD8 T cell response. MS patients treated with B cell-depleting (anti-CD20) or sphingosine 1-phosphate receptor agonist (fingolimod) therapies lack significant S-specific Ab response. Whereas S-specific CD4 and CD8 T cell responses were largely compromised by fingolimod treatment, T cell responses were robustly generated in anti-CD20-treated MS patients, but with a reduced proportion of CD4+CXCR5+ circulating follicular Th cells. These data provide novel information regarding vaccine immune response in patients with autoimmunity useful to help improve vaccine effectiveness in these populations.


Subject(s)
COVID-19 , Multiple Sclerosis , COVID-19 Vaccines , Humans , Immunologic Memory , Multiple Sclerosis/drug therapy , SARS-CoV-2
3.
Clin Neurol Neurosurg ; 215: 107210, 2022 04.
Article in English | MEDLINE | ID: covidwho-1739619

ABSTRACT

OBJECTIVES: There are indications that SARS-CoV-2 can trigger new onset or relapses of neuro-immunological disease. We report a patient with relapsing remitting multiple sclerosis (RRMS) under disease-modifying therapy (DMT) who experienced a relapse of RRMS after mild COVID-19. CASE REPORT: The patient is a 27-year-old female with RRMS who developed a third exacerbation of RRMS under DMT two weeks after mild COVID-19. Compared to previous imaging findings, new studies revealed an increase in the lesion load and an enhancing lesion over two segments in the thoracic spine. The patient profited from steroids and replacement of her previous DMT. She tolerated the first SARS-CoV-2 vaccination without side effects 6 months after the SARS-CoV-2 infection. CONCLUSIONS: SARS-CoV-2 infections can be followed by exacerbation of MS and failure of DMT. More arguments in favour than against a causal relation can be raised. Neurologist should remain vigilant for new or relapsing neuro-immunological disease following SARS-CoV-2 infections.


Subject(s)
COVID-19 , Multiple Sclerosis , Adult , COVID-19 Vaccines , Female , Humans , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/drug therapy , Recurrence , SARS-CoV-2
5.
Mult Scler Relat Disord ; 58: 103486, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1712886

ABSTRACT

BACKGROUND: Disease-modifying therapy could weaken the immune system and decrease the immune response to vaccines. It is essential to know which vaccine is more protective against SARS-CoV-2 in the multiple sclerosis population. OBJECTIVE: To assess immune response after messenger RNA BNT162b2 (Pfizer/BioNTech) and inactivated Sinovac vaccines in people with multiple sclerosis (pwMS) treated with a disease-modifying therapy (DMT) compared to healthy controls. METHODS: This single-center cross-sectional study included 526 MS patients treated with DMT, 44 healthy controls, and 21 untreated patients with MS between May 2021 and September 2021. Serum samples were collected at least two weeks after the second dose of the vaccine. RESULTS: Participants vaccinated with BNT162b2 had a higher antibody titer than the Sinovac group (95%CI=1.023 - 1.473; p< .001). No significant difference between antibody titer of pwMS without treatment and HC was found [95%CI= -0.882; - 0.935 p > .99]. In 65 adults without DMT use (HC+pwMSwithout treatment), no seronegative cases were observed in any vaccine group. In patients treated with DMT, BNT162b2 was associated with a 16.3% greater absolute risk of seropositivity than Sinovac. CONCLUSION: The mRNA vaccine could be a preferred choice of protection against SARS-CoV-2 in pMS treated with DMT.


Subject(s)
COVID-19 , Multiple Sclerosis , Adult , Antibodies, Viral , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines , Cross-Sectional Studies , Humans , Multiple Sclerosis/drug therapy , RNA, Messenger , SARS-CoV-2 , Vaccines, Inactivated/therapeutic use , Vaccines, Synthetic
6.
JAMA Neurol ; 79(4): 399-404, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1711999

ABSTRACT

Importance: The SARS-CoV-2 variant B.1.1.529 (Omicron) escapes neutralizing antibodies elicited after COVID-19 vaccination, while T-cell responses might be better conserved. It is crucial to assess how a third vaccination modifies these responses, particularly for immunocompromised patients with readily impaired antibody responses. Objective: To determine T-cell responses to the Omicron spike protein in anti-CD20-treated patients with multiple sclerosis (MS) before and after a third messenger RNA COVID-19 vaccination. Design, Setting, and Participants: In this prospective cohort study conducted from March 2021 to November 2021 at the University Hospital Geneva, adults with MS receiving anti-CD20 treatment (ocrelizumab) were identified by their treating neurologists and enrolled in the study. A total of 20 patients received their third dose of messenger RNA COVID-19 vaccine and were included in this analysis. Interventions: Blood sampling before and 1 month after the third vaccine dose. Main Outcomes and Measures: Quantification of CD4 and CD8 (cytotoxic) T cells specific for the SARS-CoV-2 spike proteins of the vaccine strain as well as the Delta and Omicron variants, comparing frequencies before and after the third vaccine dose. Results: Of 20 included patients, 11 (55%) were male, and the median (IQR) age was 45.8 (37.8-53.3) years. Spike-specific CD4 and CD8 T-cell memory against all variants were maintained in 9 to 12 patients 6 months after their second vaccination, albeit at lower median frequencies against the Delta and Omicron variants compared with the vaccine strain (CD8 T cells: Delta, 83.0%; 95% CI, 73.6-114.5; Omicron, 78.9%; 95% CI, 59.4-100.0; CD4 T cells: Delta, 72.2%; 95% CI, 67.4-90.5; Omicron, 62.5%; 95% CI, 51.0-89.0). A third dose enhanced the number of responders to all variants (11 to 15 patients) and significantly increased CD8 T-cell responses, but the frequencies of Omicron-specific CD8 T cells remained 71.1% (95% CI, 41.6-96.2) of the responses specific to the vaccine strain. Conclusions and Relevance: In this cohort study of patients with MS treated with ocrelizumab, there were robust T-cell responses recognizing spike proteins from the Delta and Omicron variants, suggesting that COVID-19 vaccination in patients taking B-cell-depleting drugs may protect them against serious complications from COVID-19 infection. T-cell response rates increased after the third dose, demonstrating the importance of a booster dose for this population.


Subject(s)
COVID-19 , Multiple Sclerosis , Adult , Antibodies, Monoclonal, Humanized , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Cohort Studies , Humans , Male , Middle Aged , Multiple Sclerosis/drug therapy , Prospective Studies , RNA, Messenger , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/therapeutic use
7.
Mult Scler Relat Disord ; 59: 103554, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1708531

ABSTRACT

BACKGROUND: Vaccination against SARS CoV-2 results in excellent personal protection against a severe course of COVID19. In People with Multiple Sclerosis (PwMS) vaccination efficacy may be reduced by immunomodulatory medications. OBJECTIVE: To assess the vaccination induced cellular and humoral immune response in PwMS receiving disease modifying therapies. METHODS: In a monocentric observational study on PwMS and patients with Neuromyelitis optica we quantified the cellular and humoral immune responses to SARS CoV-2. RESULTS: PwMS receiving glatiramer acetate, Interferon-ß, Dimethylfumarate, Cladribine or Natalizumab had intact humoral and cellular immune responses following vaccination against SARS CoV-2. B-cell depleting therapies reduced B-cell responses but did not affect T cell responses. Sphingosin-1-Phospate (S1P) inhibitors strongly reduced humoral and cellular immune responses. There was a good agreement between the Interferon gamma release assay and the T-SPOT assay used to measure viral antigen induced T-cell responses. CONCLUSION: This study demonstrates that S1P inhibitors impair the cellular and humoral immune response in SARS CoV-2 vaccination, whereas patients receiving B-cell depleting therapies mount an intact cellular immune response. These data can support clinicians in counselling their PwMS and NMOSD patients during the COVID 19 pandemic.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , COVID-19/prevention & control , Humans , Immunity, Cellular , Immunity, Humoral , Multiple Sclerosis/drug therapy , Vaccination
9.
J Neurol ; 269(3): 1316-1334, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1703834

ABSTRACT

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease affecting the central nervous system (CNS), often characterized by the accumulation of irreversible clinical disability over time. During last years, there has been a dramatic evolution in several key concepts of immune pathophysiology of MS and in the treatment of this disease. The demonstration of the strong efficacy and good safety profile of selective B-cell-depleting therapies (such as anti-CD20 monoclonal antibodies) has significantly expanded the therapeutic scenario for both relapsing and progressive MS patients with the identification of a new therapeutic target. The key role of B cells in triggering MS disease has been also pointed out, determining a shift from the traditional view of MS activity as largely being 'T-cell mediated' to the notion that MS-related pathological processes involve bi-directional interactions between several immune cell types, including B cells, both in the periphery and in the CNS. This review provides an updated overview of the involvement of B cells in the immune pathophysiology and pathology of MS. We summarize the rationale regarding the use of anti-CD20 therapies and the results of the main randomized controlled trials and observational studies investigating the efficacy and safety profile of rituximab, ocrelizumab, ofatumumab and ublituximab. Suggestions regarding vaccinations and management of MS patients during COVID-19 pandemic with anti-CD20 therapies are also discussed. Finally, therapies under investigation and future perspectives of anti-CD20 therapies are taken into consideration.


Subject(s)
COVID-19 , Multiple Sclerosis , Neurodegenerative Diseases , Humans , Multiple Sclerosis/drug therapy , Pandemics , SARS-CoV-2
10.
Eur J Neurol ; 29(5): 1538-1544, 2022 May.
Article in English | MEDLINE | ID: covidwho-1691579

ABSTRACT

BACKGROUND AND PURPOSE: SARS-CoV2 vaccination is recommended for patients with multiple sclerosis (pwMS), but response may be limited by disease-modifying-treatments (DMTs). The aim of this study was to compare the rates of humoral immune response and safety of SARS-CoV-2 vaccines in pwMS and healthy controls (HCs). METHODS: In this multicenter prospective study on 456 pwMS and 116 HCs, SARS-CoV-2-IgG response was measured 3 months after the first vaccine dose. The primary endpoint was defined as proportion of patients developing antibodies (seroconversion). Secondary endpoints included antibody level, safety and efficacy. RESULTS: Compared to 97.4% in HCs, seroconversion occurred in 96.7% (88/91) untreated pwMS, 97.1% of patients (135/139) on immunomodulatory DMTs and 61.1% (138/226; p < 0.001) on immunosuppressive DMTs. Seroconversion was lowest in patients on antiCD20 monoclonal antibodies (CD20 mAbs; 52.6%) followed by sphingosine-1-phosphate-receptor-modulators (S1PMs; 63.6%). In the S1PM subgroup, seroconversion increased with lymphocyte count (odds ratio [OR] 1.31 per 0.1 G/L; p = 0.035). In pwMS on CD20 mAbs, B-cell depletion decreased seroconversion (OR 0.52; p = 0.038), whereas time since last DMT did not. Safety of SARS-CoV-2 vaccines in pwMS was excellent. CONCLUSIONS: Humoral response to SARS-CoV2 vaccines in pwMS is generally excellent. While reduced by immunosuppressive DMTs, most importantly by B-cell-depleting CD20 mAbs and S1PMs, seroconversion is still expected in the majority of patients. SARS-CoV2 vaccination should be offered to every MS patient.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , Austria , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Humans , Immunity, Humoral , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Prospective Studies , RNA, Viral/therapeutic use , SARS-CoV-2
11.
Ideggyogy Sz ; 74(11-12): 413-424, 2021 Nov 30.
Article in Hungarian | MEDLINE | ID: covidwho-1689683

ABSTRACT

Multiple sclerosis (MS) is typically a disease of young adults. Childhood MS can be defined in patients under 18 years of age, although some authors set the limit un-der the age of 16 formerly known as "early-onset multiple sclerosis" or "juvenile multiple sclerosis", seen in 3-5% of all MS patients. Nowadays, owing to ever-evolving, better diagnostic tools and well-traced, strictly defined diagnostic criteria, childhood MS is showing an increasing incidence worldwide (0.05-2.85/100 000). MS is characterized by recurrent episodes of the central nervous system with demyelination separated in space and time. In childhood almost exclusively the relapsing-remitting (RR) type of MS occurs. Based on experience in adults, the goal in the pediatric population is also the early diagnosis, to initiate adequate DMT as soon as possible and to achieve symptom relief and good quality of life. Based on efficacy and safety studies in the adult population, inter-feron ß-1a and glatiramer acetate were first approved by the FDA and EMA for the treatment of childhood MS also. The increased relapse rate and rapid progression of childhood MS and unfavorable therapeutic response to nearly 45% of the first DMT necessitated the testing of more effective and second-line drugs in the population under 18 years of age (PARADIGMS, CONNECT). Although natalizumab was reported to be effective and well-tolerated in highly active RRMS in childhood, evidence based studies were not yet available when our patients' treatment started. In this article, we report on the successful treatment of three active RRMS patients with individually authorized off-label use of natalizumab.


Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Adolescent , Child , Glatiramer Acetate/therapeutic use , Humans , Multiple Sclerosis/diagnosis , Multiple Sclerosis/drug therapy , Natalizumab/therapeutic use , Quality of Life , Young Adult
12.
Mult Scler Relat Disord ; 57: 103345, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1683457

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
13.
Arq Neuropsiquiatr ; 79(11): 1049-1061, 2021 11.
Article in English | MEDLINE | ID: covidwho-1674093

ABSTRACT

The Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases. The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.


Subject(s)
COVID-19 , Multiple Sclerosis , Neurology , Central Nervous System , Humans , Multiple Sclerosis/drug therapy , SARS-CoV-2 , Vaccination
14.
Neurology ; 98(5): e541-e554, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1673960

ABSTRACT

BACKGROUND AND OBJECTIVES: To evaluate the immune-specific response after full severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination of patients with multiple sclerosis (MS) treated with different disease-modifying drugs by the detection of both serologic and T-cell responses. METHODS: Healthcare workers (HCWs) and patients with MS, having completed the 2-dose schedule of an mRNA-based vaccine against SARS-CoV-2 in the past 2-4 weeks, were enrolled from 2 parallel prospective studies conducted in Rome, Italy, at the National Institute for Infectious diseases Spallanzani-IRCSS and San Camillo Forlanini Hospital. Serologic response was evaluated by quantifying the region-binding domain (RBD) and neutralizing antibodies. Cell-mediated response was analyzed by a whole-blood test quantifying interferon (IFN)-γ response to spike peptides. Cells responding to spike stimulation were identified by fluorescence-activated cell sorting analysis. RESULTS: We prospectively enrolled 186 vaccinated individuals: 78 HCWs and 108 patients with MS. Twenty-eight patients with MS were treated with IFN-ß, 35 with fingolimod, 20 with cladribine, and 25 with ocrelizumab. A lower anti-RBD antibody response rate was found in patients treated with ocrelizumab (40%, p < 0.0001) and fingolimod (85.7%, p = 0.0023) compared to HCWs and patients treated with cladribine or IFN-ß. Anti-RBD antibody median titer was lower in patients treated with ocrelizumab (p < 0.0001), fingolimod (p < 0.0001), and cladribine (p = 0.010) compared to HCWs and IFN-ß-treated patients. Serum neutralizing activity was present in all the HCWs tested and in only a minority of the fingolimod-treated patients (16.6%). T-cell-specific response was detected in the majority of patients with MS (62%), albeit with significantly lower IFN-γ levels compared to HCWs. The lowest frequency of T-cell response was found in fingolimod-treated patients (14.3%). T-cell-specific response correlated with lymphocyte count and anti-RBD antibody titer (ρ = 0.554, p < 0.0001 and ρ = 0.255, p = 0.0078 respectively). IFN-γ T-cell response was mediated by both CD4+ and CD8+ T cells. DISCUSSION: mRNA vaccines induce both humoral and cell-mediated specific immune responses against spike peptides in all HCWs and in the majority of patients with MS. These results carry relevant implications for managing vaccinations, suggesting promoting vaccination in all treated patients with MS. CLASSIFICATION OF EVIDENCE: This study provides Class III data that SARS-CoV-2 mRNA vaccination induces both humoral and cell-mediated specific immune responses against viral spike proteins in a majority of patients with MS.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , CD8-Positive T-Lymphocytes , COVID-19 Vaccines , Humans , Immunity , Multiple Sclerosis/drug therapy , Prospective Studies , RNA, Messenger , SARS-CoV-2 , Vaccination
15.
Mult Scler Relat Disord ; 59: 103682, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1670926

ABSTRACT

OBJECTIVES: To determine anti-SARS-Cov2 antibodies and T-cell immunity in convalescent people with multiple sclerosis (pwMS) and/or pwMS vaccinated against Covid-19, depending on the disease modifying therapy, and in comparison to healthy controls (HC). METHODS: 75 participants were enrolled: Group 1-29 (38.7%) COVID-19 convalescent participants; Group 2-34 (45.3%) COVID-19 vaccinated; Group 3-12 (16.0%) COVID-19 convalescent participants who were later vaccinated against COVID-19. Cellular immunity was evaluated by determination of number of CD4+ and CD8+ cells secreting TNFα, IFNγ, and IL2 after stimulation with SARS-CoV-2 peptides. RESULTS: pwMS treated with ocrelizumab were less likely to develop humoral immunity after COVID-19 recovery or vaccination. No difference was observed in the cellular immunity in all studied parameters between pwMS treated with ocrelizumab compared to HC or pwMS who were treatment naïve or on first line therapies. These findings were consistent in convalescent, vaccinated, and convalescent+vaccinated participants. COVID-19 vaccinated convalescent pwMS on ocrelizumab compared to COVID-19 convalescent HC who were vaccinated did not show statistically difference in the rate of seroconversion nor titers of SARS-CoV-2 antibodies. CONCLUSION: Presence of cellular immunity in pwMS on B-cell depleting therapies is reassuring, as at least partial protection from more severe COVID-19 outcomes can be expected.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , COVID-19/prevention & control , Humans , Immunity, Cellular/physiology , Immunity, Humoral/immunology , Multiple Sclerosis/drug therapy , SARS-CoV-2/chemistry , SARS-CoV-2/immunology
16.
J Neurol Sci ; 434: 120155, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1654796

ABSTRACT

BACKGROUND: As immunity against SARS-COV-2 wanes following first and second doses of vaccination, a third dose is administered in several countries around the world. Similarly to the first doses, risks related to vaccination and humoral immune response in patients with multiple sclerosis (MS) need to be assessed. OBJECTIVE: Characterize safety and humoral immune response following the third dose of COVID-19 vaccination in a large cohort of MS patients. METHODS: We assessed the safety of the third dose of the BNT162b2-COVID-19 mRNA vaccination in adult MS patients and evaluated SARS-CoV-2 IgG response. RESULTS: Two hundred and eleven adult MS patients received a third dose of BNT162b2 COVID-19 vaccination. Median follow up time was 66 days from vaccine administration (IQR 54-84). The frequency of any adverse event was 54.5%, with the most common reported adverse events being fatigue, local pain at the injection site, fever and muscle or joint pain. Transient increase in MS symptoms was reported in 3.8% of patients, none of them requiring treatment. The rate of acute relapses treated with IV steroids was 3.3%. In a sub-group of 55 patients, 20 untreated and 35 treated with vaccination-safe disease-modifying treatments, SARS-CoV-2 IgG levels increased 21-fold (median ± SD 21.6 ± 53.05). CONCLUSIONS: The third dose of COVID-19-BNT162b2 vaccine proved safe for MS patients, with no increased risk of relapse activity. Untreated patients and patients treated with vaccination-safe disease-modifying treatments show significant increase in SARS-CoV-2 IgG levels following the third dose of vaccination.


Subject(s)
COVID-19 , Multiple Sclerosis , Adult , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Multiple Sclerosis/drug therapy , SARS-CoV-2 , Vaccination/adverse effects
17.
Mult Scler Relat Disord ; 59: 103560, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1650508

ABSTRACT

BACKGROUND: Antibody responses to SARS-CoV-2 vaccination are impaired in people with multiple sclerosis (MS) under anti-CD20 therapies. It is however unclear, whether patients who received the basic immunization prior to anti-B cell medication start respond to the COVID-19 booster dose, once B cells are depleted. AIM: To investigate the humoral response to recall antigen by COVID-19 booster vaccines in people with MS (pwMS), who recently started an anti-CD20 therapy compared to people with long-term B cell depletion. METHODS: We enrolled 15 pwMS who had received booster vaccination on anti-CD20 therapy. Of these, 11 had established anti-CD20 medications and were therefore vaccinated during a continuous state of B cell depletion (CD20-vaccine cohort). Four pwMS had received the basic immunization prior to anti-CD20 therapy commencement and only the booster dose (vaccine-CD20-vaccine cohort) under conditions of B cell depletion. We assessed SARS-CoV-2 specific antibody responses after booster vaccination among both groups and evaluated accompanying B cell numbers and proportions from the peripheral circulation. RESULTS: The booster dose of SARS-CoV-2 vaccination elicited measurable antibody responses in 18% of individuals from the CD20-vaccine cohort compared to 100% from the vaccine-CD20-vaccine cohort. Antibody-levels were significantly higher among patients from the vaccine-CD20-vaccine cohort compared to the CD20-vaccine cohort (mean 951.25 ± 1137.96 BAU/ml, vs mean 12.36 ± 11.94 BAU/ml; mean difference 938 BAU/ml (95% CI: 249-1629 BAU/ml), p <0.0001). Among the vaccine-CD20-vaccine cohort, the booster immunization led to augmentation of spike antibody levels in 75% despite concomitant B cell depletion, and values increased by 3.8 - 9.4-fold compared to basic immunization. We observed no correlation of B cell kinetics and SARS-CoV-2 antibody levels. CONCLUSION: Our study suggests that antibody production to recall COVID-19 antigens is preserved in pwMS despite concomitant anti-CD20 therapy. If corroborated in bigger cohorts, this could have implications in the management of individuals about to start B cell medications.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , COVID-19 Vaccines , Cell Count , Humans , Multiple Sclerosis/drug therapy , Pilot Projects , SARS-CoV-2
18.
Neurol Neuroimmunol Neuroinflamm ; 9(2)2022 03.
Article in English | MEDLINE | ID: covidwho-1643219

ABSTRACT

BACKGROUND AND OBJECTIVES: Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR). METHODS: A case-control (1:2) study was set up. Cases included PwMS with a confirmed diagnosis of COVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score-matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administered DMT, previous DMT sequences, or the place where the last treatment was administered. RESULTS: A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p < 0.02) with a higher risk of contracting COVID-19. Patients receiving natalizumab as last DMT (OR [95% CI]: 2.38 [1.66-3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16-2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34-2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home. DISCUSSION: This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective.


Subject(s)
COVID-19/epidemiology , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/epidemiology , Adult , Age Factors , Case-Control Studies , Dimethyl Fumarate/therapeutic use , Female , Fingolimod Hydrochloride/therapeutic use , Glatiramer Acetate/therapeutic use , Humans , Interferon-beta/therapeutic use , Italy/epidemiology , Male , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Chronic Progressive/drug therapy , Multiple Sclerosis, Chronic Progressive/epidemiology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Natalizumab/therapeutic use , Odds Ratio , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Time Factors
19.
Mult Scler Relat Disord ; 58: 103524, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1638541

ABSTRACT

BACKGROUND: The impact of disease-modifying treatments on humoral response induced by inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is understudied. METHODS: We recruited 34 persons with multiple sclerosis (MS) under fingolimod treatment and 25 healthy individuals. Anti-SARS-CoV-2 spike IgG indices were measured by ELISA in sera of participants after CoronaVac vaccinations. RESULTS: Persons with MS displayed significantly lower antibody levels and seropositivity prevalence. Persons with MS with longer fingolimod treatment durations displayed lower anti-SARS-CoV-2 indices. CONCLUSION: Our results support previous findings regarding humoral response impairing effect of fingolimod after vaccinations. Patients under fingolimod treatment may require closer monitoring for COVID-19.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , Antibody Formation , COVID-19/prevention & control , Fingolimod Hydrochloride/therapeutic use , Humans , Multiple Sclerosis/drug therapy , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination , Vaccines, Inactivated
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