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1.
Curr Opin Neurol ; 34(3): 286-294, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1895869

ABSTRACT

PURPOSE OF REVIEW: Using highly effective (HE) compounds right from the beginning of disease-modifying immunotherapy (DMT) in people with multiple sclerosis (pwMS) has gained popularity among clinicians and pwMS alike. We discuss the most recent evidence supporting this approach, and whether any of the associated risks should stop us adopting it as a default strategy. RECENT FINDINGS: With the addition of injectable ofatumumab, and the two oral sphingosine one phosphate modulators siponimod and ozanimod, ten HE DMTs are now available for pwMS, though variation in licensing status and cost may limit their use in some healthcare environments. Real World evidence based on large MS registry data suggests the superiority of early HE DMT over a slow treatment escalation approach; delaying HE DMT leads to more rapid and often irreversible disability accrual. Mechanistically, B-cell depletion, particularly memory B-cell suppression, is a common denominator closely associated with DMT efficacy. SUMMARY: The concept that HE DMTs are necessarily associated with a high risk of adverse effects, is no longer supported by the evidence. The rather predictable and manageable risk profile of most HE DMTs should lower the threshold for clinicians to discuss such treatment with pwMS as a first line approach.


Subject(s)
Multiple Sclerosis , Administration, Oral , Humans , Immunologic Factors/therapeutic use , Immunotherapy , Multiple Sclerosis/drug therapy , Treatment Outcome
2.
Neurol Sci ; 42(9): 3523-3526, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1269165

ABSTRACT

OBJECTIVES: Several concerns regard the immunogenicity of SARS-CoV-2 vaccines in people with multiple sclerosis (pwMS), since the majority of them is treated with immunomodulating/immunosuppressive disease modifying therapies. Here we report the first data on the humoral response to mRNA SARS-CoV-2 vaccine in a case series of 4 pwMS treated with ocrelizumab (OCR) as compared to a group of healthy subjects (HS). METHODS: We collected serum samples at 0, 14, 21 days after the first dose and 7 days after the second dose of BNT162b2-mRNA-Covid-19 vaccine from 55 health-care workers and 4 relapsing pwMS on OCR, with no history of Covid-19 infection. Sera were tested using the LIAISON®SARS-CoV-2 TrimericS-IgG assay (DiaSorin-S.p.A.) for the detection of IgG antibodies to SARS-CoV-2 spike protein. The anti-spike IgGtiters were expressed in Binding Antibody Units (BAU), an international standard unit. RESULTS: At baseline all subjects were negative for anti-spike IgG. Seven days after the second dose of vaccine all HS mounted a significant humoral response (geometric mean 2010.4 BAU/mL C.I. 95% 1512.7-2672) while the 4 pwMS showed a lower response (range <4.81-175 BAU/mL). DISCUSSION: Humoral response to BNT162b2-mRNA-vaccine in pwMS treated with OCR was clearly blunted. Further data are urgently needed to confirm and expand these preliminary results and to develop strategies to optimize the response to SARSCoV-2 vaccines in pwMS on OCR.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Monoclonal, Humanized , COVID-19 Vaccines , Humans , Immunogenicity, Vaccine , Multiple Sclerosis/drug therapy , RNA, Messenger , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
3.
Rev Neurol ; 72(11): 397-406, 2021 06 01.
Article in English, Spanish | MEDLINE | ID: covidwho-1248580

ABSTRACT

INTRODUCTION: For more than a decade, following the ECTRIMS Congress, the Post-ECTRIMS Meeting has been held in Spain, where neurologists with expertise in multiple sclerosis (MS) from all over the country meet to review the most relevant latest developments presented at the ECTRIMS congress (on this occasion held together with ACTRIMS). AIM: This article, published in two parts, summarises the presentations that took place at the Post-ECTRIMS Meeting, held online on 16 and 17 October 2020. DEVELOPMENT: This first part includes the latest results regarding the impact of the environment and lifestyle on risk of MS and its clinical course, and the role of epigenetics and genetic factors on these processes. Findings from preclinical and clinical research on the lymphocyte subtypes identified and the involvement of lymphoid follicles and meningeal involvement in the disease are discussed. Changes in brain structure are addressed at the microscopic and macroscopic levels, including results from high-resolution imaging techniques. The latest advances on biomarkers for the diagnosis and prognosis of MS, and on the involvement of the microbiome in these patients are also reported. Finally, results from patient registries on the impact of COVID-19 in MS patients are outlined. CONCLUSIONS: There have been new data on MS risk factors, the impact of MS at the cellular and structural level, the role of the microbiome in the disease, biomarkers, and the relationship between COVID-19 and MS.


TITLE: XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (I).Introducción. Desde hace más de una década, tras el congreso ECTRIMS, se celebra en España la reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) de toda España se reúnen para revisar las principales novedades presentadas en el ECTRIMS (en esta ocasión, celebrado junto con el ACTRIMS). Objetivo. En el presente artículo, publicado en dos partes, se resumen las ponencias que tuvieron lugar en la reunión Post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 de forma virtual. Desarrollo. En esta primera parte se incluyen los últimos resultados acerca del impacto del ambiente y el estilo de vida sobre el riesgo de EM y su curso clínico, y el papel de la epigenética y los factores genéticos sobre estos procesos. Se discuten los hallazgos en investigación preclínica y clínica sobre los subtipos de linfocitos identificados, y la implicación de los folículos linfoides y la afectación meníngea en la enfermedad. Los cambios en la estructura cerebral se abordan a nivel microscópico y macroscópico, incluyendo resultados de técnicas de imagen de alta resolución. También se presentan los últimos avances sobre biomarcadores para el diagnóstico y el pronóstico de la EM, y sobre la afectación del microbioma en estos pacientes. Por último, se esbozan los resultados de registros de pacientes sobre el impacto de la COVID-19 en los pacientes con EM. Conclusiones. Ha habido nuevos datos sobre factores de riesgo de la EM, impacto de la EM a nivel celular y estructural, papel del microbioma en la enfermedad, biomarcadores y la relación entre COVID-19 y EM.


Subject(s)
COVID-19/epidemiology , Multiple Sclerosis , Biomarkers , Central Nervous System/diagnostic imaging , Comorbidity , Environmental Exposure , Epigenesis, Genetic , Europe , Gray Matter/pathology , Humans , Life Style , Lymphocyte Subsets/immunology , Lymphoid Tissue/pathology , Meninges/pathology , Microbiota , Multiple Sclerosis/epidemiology , Multiple Sclerosis/genetics , Multiple Sclerosis/microbiology , Multiple Sclerosis/pathology , Neuroglia/pathology , Neurology/trends , Neurons/pathology , Remyelination
4.
Mult Scler Relat Disord ; 53: 103047, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1244795

ABSTRACT

BACKGROUND: The COVID-19 pandemic caused a global confinement of more than 2 months in Spain. As a result, the general population has significantly decreased their physical activity levels. The consequences of this abrupt, sedentary lifestyle in Spanish people with Multiple Sclerosis (pwMS) were unknown. Our aim was to examine the impact of COVID-19 home confinement on neuromuscular performance, functional capacity, physical self-perception, and anxiety in pwMS. METHODS: Eighteen pwMS (8:10 men/women, age: 43.41±10.88 years, Expanded Disability Status Scale: 2.85±1.34) participated in the study. Rate of force development (RFD) and maximal voluntary isometric contraction during knee extension in both legs, Timed-Up and Go test (TUG), sit-to-stand test, 6 min walk test, 10 m walk test, Physical-Self Perception Questionnaire (PSPQ) and State-Train Anxiety Inventory (STAI) were performed just before and after home confinement. RESULTS: A non-significant moderate effect (p = 0.07; ES = -0.48) was observed in the time in the sit-to-stand test compared to pre-home confinement. There was a significant increase in the time in TUG (p = 0.02; ES = -0.67). The PSQP score decreased (p = 0.01; ES = 0.79) and STAI-state increased (p = 0.01; ES = -0.65) following home confinement. CONCLUSION: Home confinement had an impact on functional capacity, physical self-perception and state anxiety. However, neuromuscular performance was not altered after home confinement.


Subject(s)
COVID-19 , Multiple Sclerosis , Adult , Female , Humans , Male , Middle Aged , Multiple Sclerosis/epidemiology , Pandemics , Physical Functional Performance , SARS-CoV-2
5.
Acta Neurol Scand ; 144(3): 229-235, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1240997

ABSTRACT

The COVID-19 pandemic has brought challenges for healthcare management of patients with multiple sclerosis (MS). Concerns regarding vulnerability to infections and disease-modifying therapies (DMTs) and their complications have been raised. Recent published guidelines on the use of DMTs in relation to COVID-19 in MS patients have been diverse between countries with lack of evidence-based facts. In Sweden, there exists a particular interest in anti-CD20 therapy as a possible risk factor for severe COVID-19 due to the large number of rituximab-treated patients off-label in the country. Rapid responses from the Swedish MS Association (SMSS) and the Swedish MS registry (SMSreg) have resulted in national guidelines on DMT use for MS patients and implementation of a COVID-19 module in the SMSreg. Recently updated guidelines also included recommendations on COVID-19 vaccination with regard to the different DMTs. Social distancing policies forced implementation of telemedicine consultation to replace in-person consultations as part of regular MS health care. Patient-reported outcome measures (PROMs) in SMSreg have been useful in this respect. This paper reports our experiences on the progress of national MS health care during the COVID-19 pandemic, in addition to offering an overview of the present scientific context.


Subject(s)
COVID-19/epidemiology , Multiple Sclerosis/epidemiology , Multiple Sclerosis/therapy , COVID-19/drug therapy , COVID-19 Vaccines , Humans , Pandemics , Physical Distancing , Rituximab/therapeutic use , Sweden/epidemiology , Telemedicine
6.
Mult Scler Relat Disord ; 52: 103028, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1233550

ABSTRACT

BACKGROUND: Some people with multiple sclerosis (pwMS) are at increased risk of severe Coronavirus disease 19 (COVID-19) and should be rapidly vaccinated. However, vaccine supplies are limited, and there are concerns about side-effects, particularly with the ChAdOx1nCoV-19 (AstraZeneca) vaccine. OBJECTIVES: To report our first experience of pwMS receiving the AstraZeneca vaccine. METHODS: Service evaluation. pwMS using the MS service at Barts Health NHS Trust were sent questionnaires to report symptoms following vaccination. RESULTS: Thirty-three responses were returned, 29/33 pwMS received a first dose of AstraZeneca vaccine, the remaining four received a first dose of BioNTech/Pfizer vaccine. All but two patients (94%) reported any symptoms including a sore arm (70%), flu-like symptoms (64%), fever (21%), fatigue (27%), and headache (21%). In more than 2/3 patients, symptoms lasted up to 48 hours, and with the exception of two pwMS reporting symptom duration of 10 and 12 days, respectively, symptoms in the remainder resolved within seven days. No severe adverse effects occurred. CONCLUSIONS: pwMS report transient symptoms following AstraZeneca vaccination, characteristics of which were similar to those reported in the non-MS population. Symptoms may be more pronounced in pwMS due to the temperature-dependent delay in impulse propagation (Uhthoff's phenomenon) due to demyelination.


Subject(s)
COVID-19 Vaccines , COVID-19 , Multiple Sclerosis , COVID-19/therapy , Humans , Immunization, Passive , Multiple Sclerosis/drug therapy , SARS-CoV-2 , Vaccination
7.
Mult Scler Relat Disord ; 52: 102939, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1233549

ABSTRACT

BACKGROUND: Infections can trigger exacerbations of multiple sclerosis (MS). The effects of the coronavirus disease 2019 (COVID-19) on MS are not known. The aim of this study was to understand the impact of COVID-19 on new and pre-existing symptoms of MS. METHODS: The COVID-19 and MS study is an ongoing community-based, prospective cohort study conducted as part of the United Kingdom MS Register. People with MS and COVID-19 were invited by email to complete a questionnaire about their MS symptoms during the infection. An MS exacerbation was defined as developing new MS symptoms and/or worsening of pre-existing MS symptoms. RESULTS: Fifty-seven percent (230/404) of participants had an MS exacerbation during their infection; 82 developed new MS symptoms, 207 experienced worsened pre-existing MS symptoms, and 59 reported both. Disease modifying therapies (DMTs) reduced the likelihood of developing new MS symptoms during the infection (OR 0.556, 95%CI 0.316-0.978). Participants with a higher pre-COVID-19 webEDSS (web-based Expanded Disability Status Scale) score (OR 1.251, 95%CI 1.060-1.478) and longer MS duration (OR 1.042, 95%CI 1.009-1.076) were more likely to experience worsening of their pre-existing MS symptoms during the infection. CONCLUSION: COVID-19 infection was associated with exacerbation of MS. DMTs reduced the chance of developing new MS symptoms during the infection.


Subject(s)
COVID-19 , Multiple Sclerosis , Humans , Immunologic Factors , Prospective Studies , SARS-CoV-2 , United Kingdom
8.
J Diet Suppl ; : 1-35, 2021 May 12.
Article in English | MEDLINE | ID: covidwho-1225581

ABSTRACT

Overall mental health depends in part on the blood-brain barrier, which regulates nutrient transfer in-and-out of the brain and its central nervous system. Lactoferrin, an innate metal-transport protein, synthesized in the substantia nigra, particularly in dopaminergic neurons and activated microglia is vital for brain physiology. Lactoferrin rapidly crosses the blood-brain barrier via receptor-mediated transcytosis and accumulates in the brain capillary endothelial cells. Lactoferrin receptors are additionally present on glioma cells, brain micro-vessels, and neurons. As a regulator of neuro-redox, microglial lactoferrin is critical for protection/repair of neurons and healthy brain function. Iron imbalance and oxidative stress are common among patients with neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, dementia, depression, and multiple sclerosis. As an endogenous iron-chelator, lactoferrin prevents iron accumulation and dopamine depletion in Parkinson's disease patients. Oral lactoferrin supplementation could modulate the p-Akt/PTEN pathway, reduce Aß deposition, and ameliorate cognitive decline in Alzheimer's disease. Novel lactoferrin-based nano-therapeutics have emerged as effective drug-delivery systems for clinical management of neurodegenerative disorders. Recent emergence of the Coronavirus disease-2019 (COVID-19) pandemic, initially considered a respiratory illness, demonstrated a broader virulence spectrum with the ability to cross the blood-brain barrier and inflict a plethora of neuropathological manifestations in the brain - the Neuro-COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are widely reported in Parkinson's disease, Alzheimer's disease, dementia, and multiple sclerosis patients with aggravated clinical outcomes. Lactoferrin, credited with several neuroprotective benefits in the brain could serve as a potential adjuvant in the clinical management of Neuro-COVID-19.

9.
Mult Scler Relat Disord ; 52: 102983, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1213442

ABSTRACT

Since the recent approval of vaccines against COVID-19, efficacy concerns emerged for MS patients treated with immunosuppressive drugs. We report our experience in four patients, under cladribine (two) or under ocrelizumab (two) treatment, all with low lymphocyte count, three of them vaccinated after 3 months from the last dose with good immune response, one (under ocrelizumab) after 2 months, without developing an appropriate title of antibodies. This experience suggests that the discriminant for the response to the vaccine is not the lymphocyte count but the timing of the vaccination.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Monoclonal, Humanized , COVID-19 Vaccines , Cladribine , Humans , SARS-CoV-2
10.
Mult Scler Relat Disord ; 52: 102968, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1188913

ABSTRACT

BACKGROUND: The pandemic of the new type of corona virus infection 2019 [Covid-19] also affect people with Multiple Sclerosis (pwMS). Currently, the accumulating information on the effects of the infection regarding the demographic and clinical characteristics of the disease, as well as outcomes within different DMTs¸ enable us to have better practices on the management of the Covid-19 infection in pwMS. OBJECTIVE: To investigate the incidence of coronavirus disease 2019 (Covid-19) and to reveal the relationship between the demographic-clinical and therapeutic features and the outcome of Covid-19 infection in a multi-center national cohort of pwMS. METHODS: The Turkish Neurological Society-MS Study Group in association with the Italian MuSC-19 Study Group initiated this study. A web-based electronic Case Report Form (eCRF) of Study-MuSC-19 were used to collect the data. The demographic data and MS histories of the patients were obtained from the file tracking forms of the relevant clinics. RESULTS: 309 MS patients with confirmed Covid-19 infection were included in this study. Two hundred nineteen (219) were females (70.9%). The mean age was 36.9, ranging from 18 to 66, 194 of them (62.8%) were under 40. The clinical phenotype was relapsing-remitting in 277 (89.6%) and progressive in 32 (10.4%). Disease duration ranged from 0.2 years to 31.4 years. The median EDSS was 1.5, ranging from 0 to 8.5. The EDSS score was<= 1 in 134 (43%) of the patients. 91.6% of the patients were on a DMT, Fingolimod was the most frequently used drug (22.0%), followed by Interferon (20.1%). The comorbidity rate is 11.7%. We were not able to detect any significant association of DMTs with Covid-19 severity. CONCLUSION: The Turkish MS-Covid-19 cohort had confirmed that pwMS are not at risk of having a more severe COVID-19 outcome irrespective of the DMT that they are treated. In addition, due to being a younger population with less comorbidities most had a mild disease further highlight that the only associated risk factors for having a moderate to severe COVID-19 course are similar with the general population such as having comorbid conditions and being older.


Subject(s)
COVID-19 , Multiple Sclerosis , Adult , Cohort Studies , Female , Fingolimod Hydrochloride , Humans , SARS-CoV-2
11.
J Neurol ; 268(11): 3975-3979, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1182249

ABSTRACT

During the COVID-19 pandemic, concerns raised regarding the use of immunosuppressants in multiple sclerosis, even if current data do not support an increased risk of infection. Although fingolimod can be temporarily suspended during COVID-19, the benefit-risk balance of suspension can be challenging. Till now, no adverse events have been described after the resumption of fingolimod, following a previous discontinuation. We report the occurrence of atrioventricular block following fingolimod restart. Fingolimod acts on sphingosine-1-phosphate-axis, a pathway that is altered with COVID-19 and hypoxic conditions. Herein we discuss how these metabolic changes may have influenced fingolimod pharmacology leading to a cardiac event.


Subject(s)
Atrioventricular Block , COVID-19 , Atrioventricular Block/chemically induced , Fingolimod Hydrochloride/adverse effects , Humans , Lysophospholipids , Pandemics , SARS-CoV-2 , Sphingosine/analogs & derivatives
12.
Mult Scler Relat Disord ; 51: 102908, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1164244

ABSTRACT

BACKGROUND: The SARS-CoV-2 pandemic impact on people with Multiple Sclerosis (pwMS) continues to worry. The disease modifying therapies in pwMS can add a more severe risk of infection when compared to the general population. Alemtuzumab is an anti-CD52 monoclonal antibody and it is one of the most immunosuppressive drugs used in Multiple Sclerosis (MS). CASE DESCRIPTION: We present a case of Covid-19 infection that occurred in a 24-year-old woman with MS and treated with alemtuzumab. The infection occurred 4 months after administration of the first course of alemtuzumab and had a benign course with subsequent development of antibodies. Furthermore, we present a brief review of the literature on similar published cases. DISCUSSION: We reviewed 17 articles concerning COVID-19 infection in MS patients in treatment with Alemtuzumab. In our case and all screened cases no severe course of disease was noted and no fatality was observed. Systematic compilation of this observation comforts clinicians about the course of Covid-19 infection despite alemtuzumab immunosuppressive treatment CONCLUSIONS: The risk of serious COVID-19 disease in MS patients treated with alemtuzumab is unknown. Physicians need to monitor carefully pwMS treated with alemtuzumab and to consider COVID-19 infection related relapse in the MS patients. Further research is recommended to evaluate the beneficial-risk profile of alemtuzumab in pandemic era.


Subject(s)
COVID-19 , Multiple Sclerosis , Adult , Alemtuzumab/therapeutic use , Female , Humans , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Pandemics , SARS-CoV-2 , Young Adult
13.
Arch Pharm (Weinheim) ; 354(4): e2000378, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1162498

ABSTRACT

Many diseases as well as acute conditions can lead to fatigue, which can be either temporary or chronic in nature. Acute fatigue develops frequently after physical exercise or after alcohol hangover, whereas microbial infections such as influenza or COVID-19 and chronic diseases like Parkinson's disease or multiple sclerosis are often associated with chronic fatigue. Oxidative stress and a resulting disturbance of mitochondrial function are likely to be common denominators for many forms of fatigue, and antioxidant treatments have been shown to be effective in alleviating the symptoms of fatigue. In this study, we review the role of reactive oxygen and nitrogen species in fatigue and the antioxidant effects of the intake of molecular hydrogen. We propose that molecular hydrogen is well suited for the treatment of temporary and chronic forms of oxidative stress-associated fatigue.


Subject(s)
COVID-19 , Fatigue , Hydrogen , Oxidative Stress , Antioxidants/metabolism , Antioxidants/pharmacology , COVID-19/metabolism , COVID-19/physiopathology , Fatigue/etiology , Fatigue/metabolism , Fatigue/therapy , Humans , Hydrogen/metabolism , Hydrogen/pharmacology , Nitrogen , Oxidative Stress/drug effects , Oxidative Stress/physiology , Quantitative Structure-Activity Relationship , Reactive Oxygen Species , SARS-CoV-2
14.
Mult Scler Relat Disord ; 51: 102928, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1157625

ABSTRACT

BACKGROUND: The current coronavirus disease (COVID-19) pandemic makes it difficult to obtain physical therapy in rehabilitation centres, particularly for persons with multiple sclerosis (pwMS), who are a population at high risk, since viral infections may contribute to MS exacerbations and relapses. Active video games could be a way to maintain physical therapy at home as part of the rehabilitation. The aim of this review is to summarise the current best evidence for the effectiveness of home-based active video games on gait and balance, user compliance, feasibility and safety for pwMS. METHODS: We searched for studies in five databases (PubMed, Scopus, Cochrane, CINAHL and Science direct) up to October 2020. Selection of studies, extraction of data and methodological quality assessment through the PEDro scale were made independently by two authors and discussed with a third author. RESULTS: Nine studies were included in this systematic review. We found significant improvements in balance; results were mixed concerning mobility, physical activity and gait. Home-based active video games are feasible and safe, with good compliance and adherence. The methodological quality of the studies was moderate (PEDro scale: 5.3 ± 2). CONCLUSION: Overall, home-based active video games were found safe and effective improving static and dynamic balance in pwMS. Compliance was good, probably because it is a motivating and enjoyable training. Active video games can be a relevant alternative for physical rehabilitation at home in pwMS. Future studies should follow more rigorous methodological standards (larger sample sizes, more randomised controlled trials) to improve the quality of evidence and include cost-effectiveness in the analysis.


Subject(s)
COVID-19 , Multiple Sclerosis , Video Games , Gait , Humans , Multiple Sclerosis/therapy , Quality of Life , SARS-CoV-2
15.
J Clin Med ; 10(6)2021 Mar 16.
Article in English | MEDLINE | ID: covidwho-1136516

ABSTRACT

Physical disability impacts psychosocial wellbeing in people with multiple sclerosis. However, the role of physical activity in this context is still debated. By taking advantage of a previous survey, conducted online from 22 April to 7 May 2020, we performed a post-hoc analysis with the aim to assess the associations between disability, physical exercise, and mental health in multiple sclerosis. We retrieved the following data: (i) sociodemographic information, (ii) changes in lifestyle (including exercise), (iii) physical disability, as measured with the Patient-Determined Disease Steps scale, and (iv) anxiety feelings and depressive symptoms assessed via the items included in the Quality of Life in Neurological Disorders measurement system. Examination of the interaction plot showed that the effect of disability on depression, but not on anxious symptoms, was significant for all levels of physical exercise (low: b = 1.22, 95% C.I. 0.85, 1.58, p < 0.001; moderate: b = 0.95, 95% C.I. 0.66, 1.24, p < 0.001; and high: b = 0.68, 95% C.I. 0.24, 1.13, p = 0.003). Based on these data, we can conclude that disability significantly impacted depression during the COVID-19 pandemic, with physical activity playing a moderating role. Our results suggest that favoring exercise in multiple sclerosis (MS) would ameliorate psychological wellbeing regardless of the level of physical disability.

16.
Mult Scler Relat Disord ; 51: 102886, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1118600

ABSTRACT

BACKGROUND: There is no data regarding COVID-19 in Multiple Sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients in Latin America. OBJECTIVE: The objective of this study was to describe the clinical characteristics and outcomes of patients included in RELACOEM, a LATAM registry of MS and NMOSD patients infected with COVID-19. METHODS: RELACOEM is a longitudinal, strictly observational registry of MS and NMOSD patients who suffer COVID-19 and Dengue in LATAM. Inclusion criteria to the registry were either: (1) a biologically confirmed COVID-19 diagnosis based on a positive result of a COVID-19 polymerase chain reaction (PCR) test on a nasopharyngeal swab; or (2) COVID-19-typical symptoms (triad of cough, fever, and asthenia) in an epidemic zone of COVID-19. Descriptive statistics were performed on demographic and clinical variables. The cohort was later stratified for MS and NMOSD and univariate and multivariate logistic regression analysis was performed to identify variables associated with hospitalizations/intensive critical units (ICU) admission. RESULTS: 145 patients were included in the registry from 15 countries and 51 treating physicians. A total of 129 (89%) were MS patients and 16 (11%) NMOSD. 81.4% patients had confirmed COVID-19 and 18.6% were suspected cases. 23 (15.8%) patients were hospitalized, 9 (6.2%) required ICU and 5 (3.4 %) died due to COVID-19. In MS patients, greater age (OR 1.17, 95% CI 1.05 - 1.25) and disease duration (OR 1.39, 95%CI 1.14-1.69) were associated with hospitalization/ICU. In NMOSD patients, a greater age (54.3 vs. 36 years, p=<0.001), increased EDSS (5.5 vs 2.9, p=0.0012) and disease duration (18.5 vs. 10.3 years, p=0.001) were significantly associated with hospitalization/ICU. CONCLUSION: we found that in MS patients, age and disease duration was associated with hospitalization and ICU admission requirement, while age, disease duration and EDSS was associated in NMOSD.


Subject(s)
COVID-19 , Multiple Sclerosis , Neuromyelitis Optica , COVID-19 Testing , Humans , Latin America/epidemiology , Multiple Sclerosis/complications , Multiple Sclerosis/epidemiology , Neuromyelitis Optica/epidemiology , SARS-CoV-2
17.
Int J Mol Sci ; 22(4)2021 Feb 11.
Article in English | MEDLINE | ID: covidwho-1079664

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global challenge. Currently, there is some information on the consequences of COVID-19 infection in multiple sclerosis (MS) patients, as it is a newly discovered coronavirus, but its far-reaching effects on participation in neurodegenerative diseases seem to be significant. Recent cases reports showed that SARS-CoV-2 may be responsible for initiating the demyelination process in people who previously had no symptoms associated with any nervous system disorders. It is presently known that infection of SARS-CoV-2 evokes cytokine storm syndrome, which may be one of the factors leading to the acute cerebrovascular disease. One of the substantial problems is the coexistence of cerebrovascular disease and MS in an individual's life span. Epidemiological studies showed an enhanced risk of death rate from vascular disabilities in MS patients of approximately 30%. It has been demonstrated that patients with severe SARS-CoV-2 infection usually show increased levels of D-dimer, fibrinogen, C-reactive protein (CRP), and overactivation of blood platelets, which are essential elements of prothrombotic events. In this review, the latest knowledge gathered during an ongoing pandemic of SARS-CoV-2 infection on the neurodegeneration processes in MS is discussed.


Subject(s)
COVID-19/complications , Multiple Sclerosis/complications , Neurodegenerative Diseases/etiology , Animals , COVID-19/pathology , COVID-19/virology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/pathology , Cytokine Release Syndrome/virology , Humans , Multiple Sclerosis/pathology , Multiple Sclerosis/virology , Neurodegenerative Diseases/pathology , Neurodegenerative Diseases/virology , SARS-CoV-2/isolation & purification , Thrombosis/etiology , Thrombosis/pathology
18.
Ann Neurol ; 89(4): 780-789, 2021 04.
Article in English | MEDLINE | ID: covidwho-1070695

ABSTRACT

OBJECTIVE: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). METHODS: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. RESULTS: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. INTERPRETATION: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists. ANN NEUROL 2021;89:780-789.


Subject(s)
COVID-19/physiopathology , Hospitalization/statistics & numerical data , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , COVID-19/mortality , Dimethyl Fumarate/therapeutic use , Female , Fingolimod Hydrochloride/therapeutic use , Humans , Immunologic Factors/therapeutic use , Intensive Care Units/statistics & numerical data , Interferons/therapeutic use , Male , Middle Aged , Mortality , Multiple Sclerosis/complications , Natalizumab/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Young Adult
19.
Vaccines (Basel) ; 9(2)2021 Jan 28.
Article in English | MEDLINE | ID: covidwho-1055124

ABSTRACT

Several concerns have been raised about the use of immunodepleting agents including alemtuzumab, cladribine and CD20-depleting antibodies in people with multiple sclerosis (pwMS) during the coronavirus disease (COVID) 2019 pandemic. As the end of the pandemic is not yet in sight, vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) may be an elegant strategy to overcome the potential hazards associated with initiating and continuing treatment with immune-depleting agents. In this review, we summarize the immunological effects of immune-depleting therapy and underlying considerations for the hitherto existing recommendations that suggest a restricted use of immune-deleting therapies during the pandemic. Moreover, we critically discuss open questions regarding vaccination in general and against SARS-CoV-2 in pwMS.

20.
QJM ; 114(10): 691-697, 2021 Dec 20.
Article in English | MEDLINE | ID: covidwho-1041817

ABSTRACT

Beta interferons (IFN-ß) are pleiotropic cytokines with antiviral properties. They play important roles in the pathogenesis of multiple sclerosis (MS), an incurable immune-mediated disorder of the central nervous system. The clinical expression of MS is heterogeneous, with relapses of neuroinflammation and with disability accrual in considerable part unrelated to the attacks. The injectable recombinant IFN-ß preparations are the first approved disease-modifying treatments for MS. They have moderate efficacy in reducing the frequency of relapses, but good long-term cost-efficacy and safety profiles, so are still widely used. They have some tolerability and adherence issues, partly mitigated in recent years by the introduction of a PEGylated formulation and use of 'smart' autoinjector devices. Their general impact on long-term disability is modest but could be further improved by developing accurate tools for identifying the patient profile of best responders to IFN-ß. Here, we present the IFN-ß-based immunomodulatory therapeutic approaches in MS, highlighting their place in the current coronavirus disease (COVID-19) pandemic. The potential role of IFN-ß in the treatment of COVID-19 is also briefly discussed.


Subject(s)
COVID-19 , Immunotherapy , Interferon-beta/therapeutic use , Multiple Sclerosis , COVID-19/drug therapy , Humans , Multiple Sclerosis/drug therapy , Pandemics
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