Research COVID-19 and its Outcomes in Multiple Sclerosis Patients

Background: Coronavirus Disease 2019 (COVID-19) is a highly contagious disease that resulted in 4533645 deaths until September first, 2021. Multiple Sclerosis (MS) patients receive immunosuppressive drugs. Thus, there is a concern that these drugs will reduce the patient's immune system resistance against COVID19. Objective(s): This study aimed to evaluate the epidemiology of COVID19 and its impact on MS patients in our university hospital in Tehran City, Iran. Material(s) and Method(s): A cross-sectional study was conducted based on hospital-based registry data from May 2020 to March 2021. Among more than 500 registered MS patients in Imam Khomeini Hospital in Tehran City, Iran, referring within our study period, 84 patients reported SARS-COV2 infection. The diagnosis of MS was confirmed by the McDonald criteria. Moreover, the diagnosis of COVID-19 in MS patients was established by the real-time-PCR technique and chest computed tomography. Result(s): Out of 84 MS patients with SARS-COV2 infection, 55(65.5%) were women, and their mean age was 37.48 years. The most commonly used medications by MS patients were Rituximab 20 (26.3%) and Dimethyl Fumarate 14(18.4%). Totally, 9(10.8%) of the patients needed to be hospitalized due to COVID-19, with a mean hospitalization duration of 5.88 days. A total of 1 (1.2%) death was reported. Conclusion(s): Compared to the healthy population, COVID-19 is not more serious in MS patients. Most MS patients with COVID-19 infection were not hospitalized and continued their medication during the infection.Copyright © 2022 The Authors. This is an open access article under the CC-By-NC license. All Rights Reserved.

Working with Individuals with Multiple Sclerosis During the New Normal

This chapter is a discussion on working with individuals with multiple sclerosis (MS) during the new normal that has been occasioned by the ongoing coronavirus disease-19 (COVID-19) pandemic. Due to the pandemic, many jobs have been lost and people with disabilities have faced significantly higher rates of unemployment than have those without disabilities. This chapter provides insights and strategies to help facilitate and promote new directions for serving those with MS regarding topics such as remote employment and service delivery for individuals with MS, redesigning workspaces for safe working conditions, and insights into new accommodation requirements/strategies in the new normal based on the existing legal frameworks. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Quality of life and mental health in multiple sclerosis patients during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic had a profound impact on mental health symptoms and quality of life (QoL) in the general population due to necessary public health restrictions such as social distancing. The psychosocial effect of the pandemic on vulnerable groups such as people living with Multiple Sclerosis (PwMS) has been scarcely explored in countries with additional socioeconomical burdens such as access to healthcare disparities METHODS: A questionnaire exploring sociodemographic variables, quality of life, mental health determinants and sleep quality was applied to 92 PwMS to explore changes prior and during the pandemic regarding these domains RESULTS: 58.8% of the subjects were female, median age was 37.1 (± 8.5) years and relapsing-remitting MS was the predominant clinical subtype (83.5%). Unemployment rate significantly increased during the pandemic (12.3% vs 27.8%; p= 0.001). Only 46.4% received medical follow-up care during the pandemic. QoL was affected predominantly due to limitations in instrumented activities of daily life (IADL). Neuropsychiatric symptoms, requiring healthcare during the pandemic, anxiety prior to the pandemic and restricted IADL were predictors of MS-related physical impact worsening, while decreased physical/emotional wellbeing selfcare, neuropsychiatric symptoms, bad sleep quality, anxiety prior to the pandemic and restricted non-instrumental ADL predicted aggravation of MS-related psychological impact measured by the MSIS-29. Curiously, specific items regarding anxiety were more prevalent prior to the pandemic (anxious mood; p=0.02, helplessness; p=0.01), sleep problems; p=0.001 and cardiovascular symptoms; p=0.001, nevertheless, stability was observed for most items. Importantly, 77.3% of PwMS reported at least one neuropsychiatric symptom CONCLUSION: The deleterious effects of the COVID-19 pandemic on psychosocial wellbeing in PwMS, QoL and mental health outcomes are frequently overseen in vulnerable populations such as PwMS. Albeit the limitations of this study, our results may help implement policies that prevent negative outcomes on psychosocial wellbeing due to public health measures (e.g., social distancing) in MS and other neurological diseases that inexorably need constant follow-up.

Neurological Complications Following COVID-19 Vaccination.

PURPOSE OF REVIEW: A variety of neurological complications have been reported following the widespread use of the COVID-19 vaccines which may lead to vaccine hesitancy and serve as a major barrier to the public health aim of achieving protective herd immunity by vaccination. In this article, we review the available evidence regarding these neurological adverse events reported, to provide clarity regarding the same so that unfounded fears maybe put to rest. RECENT FINDINGS: There is a greater than expected occurrence of severe neurological adverse events such as cortical sinus venous thrombosis, Bell's palsy, transverse myelitis, and Guillain-Barré syndromes along with other common effects such as headaches following different kinds of COVID-19 vaccination. Precipitation of new onset demyelinating brain lesions with or without detection of specific antibodies and worsening of pre-existing neurological disorders (like epilepsy, multiple sclerosis) are also a matter of great concern though no conclusive evidence implicating the vaccines is available as of now. The COVID-19 pandemic is far from being over. Till such time that a truly effective anti-viral drug is discovered, or an appropriate therapeutic strategy is developed, COVID-appropriate behavior and highly effective mass vaccination remain the only weapons in our armamentarium to fight this deadly disease. As often occurs with most therapeutic means for the treatment and prevention of any disease, vaccination against COVID-19 has its hazards. These range from the most trivial ones like fever, local pain and myalgias to several potentially serious cardiac and neurological complications. The latter group includes conditions like cerebral venous thrombosis (curiously often with thrombocytopenia), transverse myelitis and acute inflammatory demyelinating polyneuropathy amongst others. Fortunately, the number of reported patients with any of these serious complications is far too low for the total number of people vaccinated. Hence, the current evidence suggests that the benefits of vaccination far outweigh the risk of these events in majority of the patients. As of now, available evidence also does not recommend withholding vaccination in patients with pre-existing neurological disorders like epilepsy and MS, though adenoviral vaccines should be avoided in those with history of thrombotic events.

COVID-19 and its outcomes in multiple sclerosis patients

Background: Coronavirus Disease 2019 (COVID-19) is a highly contagious disease that resulted in 4533645 deaths until September first, 2021. Multiple Sclerosis (MS) patients receive immunosuppressive drugs. Thus, there is a concern that these drugs will reduce the patient's immune system resistance against COVID19. Objective(s): This study aimed to evaluate the epidemiology of COVID19 and its impact on MS patients in our university hospital in Tehran City, Iran. Material(s) and Method(s): A cross-sectional study was conducted based on hospital-based registry data from May 2020 to March 2021. Among more than 500 registered MS patients in Imam Khomeini Hospital in Tehran City, Iran, referring within our study period, 84 patients reported SARS-COV2 infection. The diagnosis of MS was confirmed by the McDonald criteria. Moreover, the diagnosis of COVID-19 in MS patients was established by the real-time-PCR technique and chest computed tomography. Result(s): Out of 84 MS patients with SARS-COV2 infection, 55(65.5%) were women, and their mean age was 37.48 years. The most commonly used medications by MS patients were Rituximab 20 (26.3%) and Dimethyl Fumarate 14(18.4%). Totally, 9(10.8%) of the patients needed to be hospitalized due to COVID-19, with a mean hospitalization duration of 5.88 days. A total of 1 (1.2%) death was reported. Conclusion(s): Compared to the healthy population, COVID-19 is not more serious in MS patients. Most MS patients with COVID- 19 infection were not hospitalized and continued their medication during the infection.

Clinical onset of CNS demyelinating disease after COVID-19 vaccination: denovo disease?

BACKGROUND: Clinical onset of multiple sclerosis (MSpostvacc) and myelin-oligodendrocyte-glycoprotein-antibody-associated disease (MOGADpostvacc) has been reported in association with SARS-CoV-2-vaccination. There is uncertainty as to whether this is causality (denovo disease) or temporal coincidence (manifestation of a preexisting, subclinical neuroinflammation). OBJECTIVES: Comparing the clinical characteristics of MSpostvacc-patients versus patients with MS (PwMS) whose clinical onset occurred independently of vaccination (MSreference). METHODS: Consecutive patients with clinical onset ≤30 days after SARS-CoV-2-vaccination were included. Clinical data, cerebrospinal fluid (CSF) parameters and magnetic resonance imaging (MRI) as well as optical coherence tomography (OCT) data were compared to an age- and sex-matched MSreference-cohort. RESULTS: We identified 5 MSpostvacc and 1 MOGADpostvacc patients who developed their clinical onset ≤ 30 days after SARS-CoV-2-vaccination. Clinical characteristics, CSF, MRI and OCT parameters from MSpostvacc patients were comparable to the MSreference cohort and showed evidence of preexisting subclinical CNS disease. The single case with MOGADpostvacc clearly differed from PwMS in higher CSF cell counts, remission of MRI lesions during follow-up, and absence of oligoclonal bands. CONCLUSIONS: Our case series indicates that MSpostvacc patients showed a rather typical initial manifestation in temporal association with SARS-CoV-2-vaccination and harbored preexisting subclinical neuroinflammation. This argues against the denovo development of MS in this cohort.

Response to COVID-19 booster vaccinations in seronegative people with multiple sclerosis.

BACKGROUND: People with MS treated with anti-CD20 therapies and fingolimod often have attenuated responses to initial COVID-19 vaccination. However, uncertainties remain about the benefit of a 3rd (booster) COVID-19 vaccine in this group. METHODS: PwMS without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2-12 weeks following COVID-19 vaccine 3. Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. RESULTS: Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There was no association between laboratory evidence of prior COVID-19 and seroconversion following vaccine 3. CONCLUSIONS: Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine.

Review Article: Psychological Distress in Patients With Multiple Sclerosis and Epilepsy in the COVID-19 Pandemic: A Systematic Review

Background: The COVID-19 pandemic can cause various anxiety, fear, and tension in society. The negative impact of the pandemic is not limited to physical health problems. It can generate serious consequences, such as anxiety, depression, and stress, especially neurological diseases. Objectives: The present study investigated depression, anxiety, and stress in patients with MS and epilepsy during the COVID-19 pandemic. Materials & Methods: In this study, the keywords depression, anxiety, stress, multiple sclerosis, epilepsy, and COVID-19 in the title and of articles published in 2020 (May) and 2021 (July) in reputable international scientific databases, including Google Scholar, PubMed, Scopus, EMBASE, and PsycINFO were searched. The PRISMA checklist was used to review and control the quality of articles. Results: Overall, 394 English articles were retrieved. Finally, 27 final articles were selected for comprehensive review and data extraction. The obtained results suggested that patients with MS and epilepsy experienced depression, anxiety, stress, fear, poor sleep quality, mental fatigue, and poor quality of life during the COVID-19 pandemic. Quarantine has limited patients’ access to medication and treatment, resulting in increased seizures and disease severity. Conclusion: The COVID-19 pandemic reduced patients’ mental health with MS and epilepsy. The psychological consequences of the outbreak of COVID-19 might be associated with patients with MS and epilepsy for years;thus, it is necessary to adopt psychological interventions to reduce psychological distress in these patients © 2018 The Authors. This is an open access article under the CC-By-NC license

Research Paper: COVID-19 and its Outcomes in Multiple Sclerosis Patients

Background: Coronavirus Disease 2019 (COVID-19) is a highly contagious disease that resulted in 4533645 deaths until September first, 2021. Multiple Sclerosis (MS) patients receive immunosuppressive drugs. Thus, there is a concern that these drugs will reduce the patient's immune system resistance against COVID19. Objectives: This study aimed to evaluate the epidemiology of COVID19 and its impact on MS patients in our university hospital in Tehran City, Iran. Materials & Methods: A cross-sectional study was conducted based on hospital-based registry data from May 2020 to March 2021. Among more than 500 registered MS patients in Imam Khomeini Hospital in Tehran City, Iran, referring within our study period, 84 patients reported SARS-COV2 infection. The diagnosis of MS was confirmed by the McDonald criteria. Moreover, the diagnosis of COVID-19 in MS patients was established by the real-time-PCR technique and chest computed tomography. Results: Out of 84 MS patients with SARS-COV2 infection, 55(65.5%) were women, and their mean age was 37.48 years. The most commonly used medications by MS patients were Rituximab 20 (26.3%) and Dimethyl Fumarate 14(18.4%). Totally, 9(10.8%) of the patients needed to be hospitalized due to COVID-19, with a mean hospitalization duration of 5.88 days. A total of 1 (1.2%) death was reported. Conclusion: Compared to the healthy population, COVID-19 is not more serious in MS patients. Most MS patients with COVID-19 infection were not hospitalized and continued their medication during the infection. © 2022 The Authors. This is an open access article under the CC-By-NC license. All Rights Reserved.

The Multiple Sclerosis Data Alliance Catalogue: Enabling Web-Based Discovery of Metadata from Real-World Multiple Sclerosis Data Sources.

BACKGROUND: One of the major objectives of the Multiple Sclerosis Data Alliance (MSDA) is to enable better discovery of multiple sclerosis (MS) real-world data (RWD). METHODS: We implemented the MSDA Catalogue, which is available worldwide. The current version of the MSDA Catalogue collects descriptive information on governance, purpose, inclusion criteria, procedures for data quality control, and how and which data are collected, including the use of e-health technologies and data on collection of COVID-19 variables. The current cataloguing procedure is performed in several manual steps, securing an effective catalogue. RESULTS: Herein we summarize the status of the MSDA Catalogue as of January 6, 2021. To date, 38 data sources across five continents are included in the MSDA Catalogue. These data sources differ in purpose, maturity, and variables collected, but this landscaping effort shows that there is substantial alignment on some domains. The MSDA Catalogue shows that personal data and basic disease data are the most collected categories of variables, whereas data on fatigue measurements and cognition scales are the least collected in MS registries/cohorts. CONCLUSIONS: The Web-based MSDA Catalogue provides strategic overview and allows authorized end users to browse metadata profiles of data cohorts and data sources. There are many existing and arising RWD sources in MS. Detailed cataloguing of MS RWD is a first and useful step toward reducing the time needed to discover MS RWD sets and promoting collaboration.

The Effects of Vitamin D on Immune System and Inflammatory Diseases.

Immune cells, including dendritic cells, macrophages, and T and B cells, express the vitamin D receptor and 1α-hydroxylase. In vitro studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, has an anti-inflammatory effect. Recent epidemiological evidence has indicated a significant association between vitamin D deficiency and an increased incidence, or aggravation, of infectious diseases and inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, the impact of vitamin D on treatment and prevention, particularly in infectious diseases such as the 2019 coronavirus disease (COVID-19), remains controversial. Here, we review recent evidence associated with the relationship between vitamin D and inflammatory diseases and describe the underlying immunomodulatory effect of vitamin D.

The Immunological Therapeutic Strategies for Controlling Multiple Sclerosis: Considerations during the COVID-19 Pandemic.

A growing body of evidence initially suggested that patients with multiple sclerosis (MS) might be more susceptible to coronavirus disease 2019 (COVID-19). Moreover, it was speculated that patients with MS treated with immunosuppressive drugs might be at risk to develop a severe diseases course after infection with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2). However, the recently published data have shown that MS patients do not have a higher risk for severe COVID-19. Although there is no indication that patients with MS and immunomodulatory/immunosuppressive therapy are generally at a higher risk of severe COVID-19, it is currently being emphasized that the hazards of poorly treated MS may outweigh the putative COVID-19 dangers. In this review, we discuss the challenges and considerations for MS patients in the COVID-19 pandemic.

Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders.

Over recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner. Firstly, MSCs were successfully isolated from human bone marrow (BM), but in the next steps, they were also extracted from other sources, mostly from the umbilical cord (UC) and adipose tissue (AT). The International Society for Cellular Therapy (ISCT) has suggested minimum criteria to identify and characterize MSCs as follows: plastic adherence, surface expression of CD73, D90, CD105 in the lack of expression of CD14, CD34, CD45, and human leucocyte antigen-DR (HLA-DR), and also the capability to differentiate to multiple cell types including adipocyte, chondrocyte, or osteoblast in vitro depends on culture conditions. However, these distinct properties, including self-renewability, multipotency, and easy accessibility are just one side of the coin; another side is their huge secretome which is comprised of hundreds of mediators, cytokines, and signaling molecules and can effectively modulate the inflammatory responses and control the infiltration process that finally leads to a regulated tissue repair/healing or regeneration process. MSC-mediated immunomodulation is a direct result of a harmonic synergy of MSC-released signaling molecules (i.e., mediators, cytokines, and chemokines), the reaction of immune cells and other target cells to those molecules, and also feedback in the MSC-molecule-target cell axis. These features make MSCs a respectable and eligible therapeutic candidate to be evaluated in immune-mediated disorders, such as graft versus host diseases (GVHD), multiple sclerosis (MS), Crohn's disease (CD), and osteoarthritis (OA), and even in immune-dysregulating infectious diseases such as the novel coronavirus disease 2019 (COVID-19). This paper discussed the therapeutic applications of MSC secretome and its biomedical aspects related to immune-mediated conditions. Sources for MSC extraction, their migration and homing properties, therapeutic molecules released by MSCs, and the pathways and molecular mechanisms possibly involved in the exceptional immunoregulatory competence of MSCs were discussed. Besides, the novel discoveries and recent findings on immunomodulatory plasticity of MSCs, clinical applications, and the methods required for their use as an effective therapeutic option in patients with immune-mediated/immune-dysregulating diseases were highlighted.

The impact of SARS-CoV2 on the anxiety levels of subjects and on the anxiety and depression levels of their parents.

BACKGROUND: The Severe Acute Respiratory Syndrome-CoV2 outbreak was announced a pandemic by the World Health Organization on March 11th, 2020. Both the pandemic itself and the restrictions were thought to create some psychological problems especially in patients with chronic illnesses such as Multiple Sclerosis (MS). This study was conducted to evaluate the impact of SARS-CoV2 pandemic on daily lives of children with MS, and the anxiety status of these patients and anxiety - depression status of their parents. METHODS: This study was performed on a group of pediatric MS patients aged 8-18 years in Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, and Child Neurology Department. Thirty patients with MS and their 30 parents were enrolled to the study. The control group consisted of 49 healthy, age- and sex-matched children and their 49 parents. The patients (and their parents) were asked to complete a web-based survey evaluating access to health care and other changes in daily life between March 11th, 2020 and June 1st, 2020. The State-Trait Anxiety Inventory (STAI) [which is composed of two parts; S-anxiety (STAI-S) and T-anxiety (STAI-T)] was administrated to the patients and healthy controls and the results were compared between the two groups to assess their anxiety levels. The Hospital Anxiety and Depression Scale (HAD) [which is composed of two parts; HAD-anxiety (HAD-A) and HAD-depression (HAD-D)] was also given to all parents. The results of the HAD tests were compared between the two groups statistically. RESULTS: The results of the web-based survey showed that 4 of 9 (44.4%) patients, who had a regular workout program, left the program and 13 (43.3%) patients put on weight during the pandemic. Twenty-two patients (73.3%) could not get direct exposure to sunlight because of the curfew. Therefore, approximately half of the patients started to take vitamin D supplement. Most of the patients (80%) thought that they had higher risk and believed that they would have severe symptoms compared to healthy people. Twenty one (70%) patients disrupted their regular health checks and the most frequent causes were identified as closure of policlinics to routine patient care (33%) and concerns of getting SARS-CoV2 infection (26,6%). Two of 3 patients who had an MS attack did not go to the doctor during this period. The mean STAI-S scores in MS patients were significantly higher compared to the healthy controls (p=<0.001). The level of S-anxiety in all patients was higher compared to the cut off value.The mean HAD A score was found to be significantly higher in them compared to the parents of healthy individuals (p = 0.001). CONCLUSION: Our results showed that children with MS had negative changes in daily life and high anxiety levels during the pandemic. Since MS patients have also psychiatric comorbidities, they may need psychosocial support especially in this period. Besides, establishment of separate health centers to be used during pandemics for children with chronic illnesses such as MS may be recommended to facilitate access to health care.

Disease-Modifying Therapies During the COVID-19 Outbreak: A Narrative Review of International and National Recommendations.

BACKGROUND: Managing multiple sclerosis (MS) during the novel coronavirus disease 2019 (COVID-19) pandemic is a challenge due to the lack of evidence from clinical studies. Disease-modifying therapies (DMTs) may affect the immune response and subsequently alter the risk of COVID-19 infections. METHODS: A literature search was conducted on the MEDLINE, Embase, and Cochrane databases. A focused Google search was also performed. Recommendations regarding the use of DMTs during the COVID-19 outbreak from national and international MS/neurology societies were identified and reviewed. RESULTS: The review included 16 recommendations from international and national MS organizations. All recommendations are based on expert opinions. The recommendations regarding DMT initiation and management during this outbreak are summarized. Moreover, the experts' views about the risk of COVID-19 infection with each DMT are discussed. CONCLUSIONS: There is significant agreement among most experts' recommendations from a variety of sources based on collective clinical experience. However, the recommendations will likely evolve because sufficient clinical data are limited. Several ongoing registries will help provide information for future recommendations.

Recovery from COVID-19 in a B-cell-depleted multiple sclerosis patient.

Approximately 200,000 multiple sclerosis (MS) patients worldwide receive B-cell-depleting immunotherapy with rituximab (anti-CD20), which eliminates the ability to generate an antibody response to new infections. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies might help viral clearance, these patients could be at risk of severe complications if infected. Here, we report on an MS patient who had received rituximab for ~3 years. The patient was examined 5 days before the onset of coronavirus disease 2019 (COVID-19) symptoms and was admitted to the hospital 2 days after. She recovered 14 days after symptom onset despite having a 0% B lymphocyte count and not developing SARS-CoV-2 immunoglobulin G (IgG) antibodies.