Immunoadsorption as maintenance therapy for refractory neuromyelitis optica spectrum disorder.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system, affecting mainly optic nerves and spinal cord. NMOSD pathophysiology is associated with anti-aquaporin-4 (AQP4) immunoglobulin G (IgG) autoantibodies. Rapid extracorporeal elimination of autoantibodies with apheresis techniques, such as immunoadsorption (IA), was proven to be an effective treatment of NMOSD attacks. Data on the long-term use of IA to prevent attacks or progression of NMOSD are lacking. Objectives: The aim of this study was to evaluate efficacy and safety of maintenance IA for preventing recurrence of NMOSD attacks in patients refractory to other immunotherapies. Design: Case study. Methods: Retrospective analysis of two female patients with severe NMOSD refractory to conventional immunotherapies was performed. Both patients had responded to tryptophan IA (Tr-IA) as attack therapy and subsequently were treated with biweekly maintenance Tr-IA. Results: Patient 1 (AQP4-IgG seropositive, age 42 years) had 1.38 attacks of optic neuritis per year within 10.1 years before commencing regular Tr-IA. With maintenance Tr-IA for 3.1 years, one mild attack occurred, which was responsive to steroid pulse therapy. Expanded Disability Status Scale (EDSS) was stable at 5.0. Visual function score of the last eye improved from 3 to 1. Patient 2 (AQP4-IgG seronegative, age 43 years) experienced 1.7 attacks per year, mainly acute myelitis and optic neuritis, during the period of 10.0 years before the start of Tr-IA. During regular Tr-IA treatment, no further NMOSD attack occurred. The patient was clinically stable without any additional immunosuppressive treatment for 5.3 years. EDSS improved from 6.0 to 5.0, and the ambulation score from 7 to 1. Tolerability of Tr-IA was good in both patients. No serious adverse events occurred during long-term clinical trajectories. Conclusion: Tr-IA was well tolerated as maintenance treatment and resulted in clinical stabilization of two patients with highly active NMOSD, who were refractory to standard drug therapy.

Association between infections, the microbiome, vaccination, and neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a devastating antibody-mediated condition of the central nervous system. As in other autoimmune diseases, there is considerable evidence to suggest that NMOSD arises from complex interactions between genetic susceptibility and environmental factors. However, whether factors like aquaporin-4-Antibody production initiate NMOSD attacks, currently remains unclear, and requires further investigation. Infectious diseases have also been proposed as possible environmental factors associated with NMOSD onset or relapses, some of which are more common in Asia and Latin America than in Europe and North America, in parallel with the higher incidence of NMOSD in these geographic locations. In this review, we examine current evidence on specific infections and vaccines associated with NMOSD onset and/or attacks, as well as the most recent data on gut microbiome composition and SARS-CoV-2 infection in NMOSD patients.

Microorganisms in Pathogenesis and Management of Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system with astrocytopathy characteristics. Antibodies against aquaporin-4 water channels which are mainly located in astrocyte podocytes play an important role in NMOSD pathogenesis. Like other autoimmune disorders, it seems that both genetic and environmental factors are involved in NMOSD risk, but the role of environmental risk factors is more significant. Infections are known to be an effective factor not only in the incidence but also in the exacerbation of autoimmune diseases. In this chapter, the roles of microorganisms in two categories of viruses and bacteria in the pathogenesis and management of NMOSD patients are discussed. In this regard the relation between infection with tuberculosis, Helicobacter pylori, Epstein-Barr virus, SARS-CoV-2, varicella-zoster virus, dengue virus, cytomegalovirus, herpes simplex virus 2 and Zika virus, as well as gut microbiome and NMOSD occurrence are mentioned. On the other hand, susceptibility of NMOSD patients for developing infectious diseases due to receiving immunosuppressive drugs and the role of infection in NMOSD attack and disease exacerbation are outlined. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Serum negative neuromyelitis optica spectrum disorder after vaxzevria vaccination: A case report

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease, targeting the central nervous system, rarely associated with vaccination. Case report: We report a case of a 47 year-old healthy woman who presented, ten days after the first dose of SARS-CoV-2 Vaccine AstraZeneca (Vaxzevria), with back pain, tetraplegia, urinary retention, dysarthria and dysphagia. The patient was diagnosed NMOSD. She underwent intravenous-corticosteroids, vein-Immunoglobulin and plasma-exchange without significant improvement . Conclusion(s): The absence of any possible related conditions, the temporal relation with anti-SARS-CoV-2 vaccination, suggest that, in our case, NMOSD may be due to the cross reaction from Vaxzevria.Copyright © 2021 The Author(s)

Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder: Onset Following Acute COVID-19 Infection, a Case Series.

BACKGROUND AND OBJECTIVES: Acute COVID-19 infection has been associated with neurological involvement. We report a case series of newly diagnosed patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) developed in a short period of time after acute COVID-19 infection. METHODS: New MS patients developing initial symptoms shortly after an acute COVID-19 infection were diagnosed based on the 2017 McDonald Criteria [Garcia-Ramos et al. in Cells, 2021]. The patients diagnosed with NMOSD met the 2015 International Panel criteria for the diagnosis of NMOSD (IPDN) [Thompson et al. in Lancet Neurol 17:162-173, 2018]. RESULTS FROM THE MS PATIENT GROUP: Ten patients were included who had developed initial MS symptoms after COVID-19 infection. Gender distribution was equal (50% male). The mean age was 28 (range 17-39) years. Average time to neurological presentation was between 2 and 6 weeks following acute COVID-19 infection. Partial transverse myelitis was the initial presentation in 40% of the cases, and 60% of patients had spinal cord lesions present at the moment of diagnosis. All patients showed enhancing lesions on brain magnetic resonance imaging (MRI). The presence of cerebrospinal fluid (CSF) oligoclonal bands was found in all six tested cases. The majority of patients (80%) were unvaccinated for COVID-19. The two vaccinated patients had received two doses of the monovalent COVID-19 messenger ribonucleic acid (mRNA) (Pfizer Biotech) vaccine and no booster, a year prior to contracting COVID-19. RESULTS FROM THE NMOSD GROUP: Two patients with NMOSD were included. Positive aquoporin-4 protein antibody (AQP-4 Ab) was detected in serum in both cases [one Enzyme Linked immunosorbent assay (ELISA) and one cell based]. Both patients had mild COVID-19 infection prior to presentation, initial neurologic symptoms presented between 3 and 6 weeks after COVID-19 infection. Neither patients were vaccinated. Both responded partially to steroids, one developed a relapse 40 days after diagnosis. CONCLUSION: COVID-19 infection has been linked to several neurological and immune-driven conditions. This study suggests that in susceptible individuals, acute COVID-19 infection may act as a trigger for developing MS and NMOSD.

First manifestation of AQP4-IgG-positive neuromyelitis optica spectrum disorder following the COVID-19 mRNA vaccine BNT162b2.

BNT162b2 is one of the effective COVID-19 vaccines. However, some researchers have also reported some neurological adverse events after the vaccination. Here, we present a case of a 52-year-old female who developed aquaporin (AQP) 4-IgG-positive neuromyelitis optica spectrum disorder (NMOSD) 14 days after the first dose of BNT162b2. She experienced the neck pain, weakness of the left arm and leg, numbness of the left hand, and impaired temperature sensation of the right leg. MRI showed T2WI hyperintense lesions in the area postrema and cervical spinal cord ranging from C1 to C6 level and Gd-enhanced lesions from C3 to C5 level; especially left lateral column was predominantly enhanced. Cell-based assays showed anti-AQP4 antibody (AQP4Ab) was positive. We diagnosed AQP4-IgG-positive NMOSD. After high-dose glucocorticoid therapy, she is showing improved symptoms. The present case was characterized by the findings that a Gd-enhanced lesion in the cervical cord localized dominantly at the left lateral column, consistent with the side of the shoulder where the vaccine was injected. Many studies suggested that AQP4-IgG-positive NMOSD development has multistep mechanisms following the blood-brain barrier (BBB) breakdown. We suspected that immune responses following vaccination lead to BBB disruptions. Through the limitedly damaged BBB, the plasma cells producing AQP4Abs might be recruited to CNS, and AQP4Abs might bind to the cervical cord and the area postrema. A population-based study revealed that neurological events following COVID-19 vaccination were less likely to be observed than COVID-19 infectious symptoms. Considering rare adverse events, clinicians need to observe any changes in patient condition.

Long-term safety of satralizumab in neuromyelitis optica spectrum disorder (NMOSD) from SAkuraSky and SAkuraStar.

BACKGROUND: This analysis evaluated long-term safety findings from the SAkuraSky and SAkuraStar studies with satralizumab in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: SAkuraSky (satralizumab in combination with baseline immunosuppressive therapy; IST) and SAkuraStar (satralizumab monotherapy) are international, multicenter, randomized, placebo-controlled, phase 3 studies consisting of a double-blind (DB) period followed by an open-label extension (OLE). The overall satralizumab treatment (OST) period safety population comprised patients receiving ≥1 dose of satralizumab in the DB and/or OLE periods (cut-off date: 22 February 2021). Safety was evaluated in the DB and OST periods. RESULTS: In the SAkuraSky DB period, patients received satralizumab (n = 41) or placebo (n = 42) in addition to stable baseline IST; 75 patients were included in the OST population. In the SAkuraStar DB period, 63 patients received satralizumab monotherapy and 32 received placebo; 91 patients were included in the OST population. Median treatment exposure in the OST period was 4.4 years (range 0.1-7.0) in SAkuraSky and 4.0 years (range 0.1-6.1) in SAkuraStar. Rates of adverse events (AEs per 100 patient-years) and serious AEs in the OST period were comparable with satralizumab and placebo in the DB periods of both studies. Similarly, overall rates of infections and serious infections were consistent between the OST and DB periods with satralizumab, with no increase in rates of infections or serious infections over time. In the OST periods, longer exposure to satralizumab was not associated with a higher risk of severe (grade ≥3) laboratory changes versus the DB periods. No deaths or anaphylactic reactions to treatment with satralizumab were reported during the OST periods of both studies. CONCLUSION: The safety profile of satralizumab as a monotherapy or in combination with IST was maintained in the OLE, and no new safety concerns versus the DB period were observed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02028884 (SAkuraSky) and NCT02073279 (SAkuraStar).

Onset of various CNS inflammatory demyelination diseases following COVID-19 vaccinations.

BACKGROUND: Since the start of COVID-19 vaccination worldwide, there have been several reports of inflammatory demyelinating diseases of the central nervous system (CNS-IDDs) following vaccination. METHODS: We prospectively collected cases of new-onset CNS-IDDs with a temporal relationship between disease onset and COVID-19 vaccination and investigated their proportion among newly registered cases of CNS-IDD over the past year. RESULTS: Among 117 cases, 10 (8.5%) had their first disease manifestation within one month following COVID-19 vaccination: 2 multiple sclerosis, 2 neuromyelitis optica spectrum disorder, 3 MOG antibody-associated disease, and 3 unclassified CNS-IDDs. CONCLUSION: This observation suggests that COVID-19 vaccination may trigger the onset of various CNS-IDDs in susceptible individuals.

The risk of infections for multiple sclerosis and neuromyelitis optica spectrum disorder disease-modifying treatments: Eighth European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop Review. April 2021.

Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.

Fulminant neuromyelitis optica spectrum disorder (NMOSD) following COVID-19 vaccination: A need for reconsideration?

During the coronavirus disease 2019 (COVID-19) pandemic, mass vaccination was a beneficial strategy in many countries. Nevertheless, reports of serious complications such as postvaccination neuromyelitis optica spectrum disorder (NMOSD) raised concerns about the safety of vaccines. Anamnart and colleagues explained postvaccination NMOSD following different vaccines, including COVID-19. To emphasize the message of this article, in this letter, we present a unique case of postvaccination NMOSD with a fulminant and fatal course, which may show a plausible relationship between COVID-19 vaccination and triggering anti-aquaporin-4 antibody (AQP4-Ab).

A Case Presenting with Neuromyelitis Optica Spectrum Disorder and Infectious Polyradiculitis Following BNT162b2 Vaccination and COVID-19.

A 37-year-old woman presented with paraparesis and paresthesia in both legs 19 and 3 days after BNT162b2 vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, respectively. Cerebrospinal fluid (CSF) analysis, nerve conduction study, electromyography, magnetic resonance imaging, and autoantibody tests were performed. Neurological examination showed hyperesthesia below the T7 level and markedly impaired bilateral leg weakness with absent deep tendon reflexes on the knees and ankles. CSF examination revealed polymorphonuclear dominant pleocytosis and elevated total protein levels. Enhancement of the pia mater in the lumbar spinal cord and positive sharp waves in the lumbar paraspinal muscles indicated infectious polyradiculitis. In contrast, a high signal intensity of intramedullary spinal cord on a T2-weighted image from C1 to conus medullaris and positive anti-aquaporin-4 antibody confirmed neuromyelitis optica spectrum disorder (NMOSD). The patient received intravenous methylprednisolone, antiviral agents, and antibiotics, followed by a tapering dose of oral prednisolone and azathioprine. Two months after treatment, she was ambulatory without assistance. The dual pathomechanism of NMOSD triggered by coronavirus disease 2019 (COVID-19) vaccination and polyradiculitis caused by SARS-CoV-2 infection may have caused atypical clinical findings in our patient. Therefore, physicians should remain alert and avoid overlooking the possibilities of diverse mechanisms associated with neurological manifestations after SARS-CoV-2 infection and COVID-19 vaccination.

Autoimmune/Inflammatory Syndrome induced by Adjuvants (ASIA): Neuromyelitis Optica Spectrum Disorder after BBIBP-Cor-V vaccine, case report

Background : Recently the term Autoimmune/Inflammatory Syndrome induced by Adjuvants has been proposed to describe different clinical conditions, among them post-vaccinal phenomena like demyelinating diseases. Objective : We aim to add knowledge on the possible association of vaccines and the development of demyelinating diseases. Case report : We present the case of a 38-year-old female that developed a brainstem syndrome after vaccination with COVID-19 BBIBP-CorV Sinopharm Vaccine. The final diagnosis after extensive work-out was Neuromyelitis Optica spectrum disorder with positive Aquaporin 4 positive antibodies;and long-term treatment with Rituximab was initiated. Conclusion : Since we are facing a large-scale vaccination, professionals should be aware of the presence of demyelinating diseases as adverse events for COVID-19 vaccine.

COVID-19 and Autoimmune Demyelinating Diseases

This chapter addresses COVID-19 in the context of patients with demyelinating disorders of the central nervous system (CNS). Multiple sclerosis (MS) is the most common CNS demyelinating disease, and SARS-CoV-2 infection in patients with MS and other autoimmune demyelinating CNS disorders causes numerous concerns. As with other infectious diseases, COVID-19 may exacerbate pathology in patients with MS. Standard therapies for MS and immunosuppressive treatments for other CNS autoimmune disorders may pose unique risks during severe COVID-19. However, preliminary findings on SARS-CoV-2 infection suggest that some MS therapies may limit the aggressive immune response underlying severe COVID-19 complications. Furthermore, infection with SARS-CoV-2 may have the potential to trigger postinfection autoimmune disorders. Here we review the current understanding of COVID-19 in patients with MS and other CNS disorders and the impact of immunomodulatory therapies on these patients. © 2021 Elsevier Inc. All rights reserved.

Post COVID-19 infection neuromyelitis optica spectrum disorder (NMOSD): A case report-based systematic review.

BACKGROUND: One of the rare neuroinflammatory disorders is Neuromyelitis optica spectrum disorder (NMOSD) which involves the central nervous system (CNS), and develops by various etiologies. There is evident that viral infections could cause neurological disorders. In this regard, novel coronavirus (COVID-19) triggers NMOSD, based on reports. We performed this systematic review to evaluate NMOSD patients following COVID-19 infection. METHODS: We collected 345 studies from PubMed (Medline), Embase, Scopus, and Web of Science databases from inception to 20 October 2021, and our inclusion criteria were English case reports/case series. Other types of Coronaviridae virus studies, review articles, articles written in any language other than English were excluded as well. RESULTS: 11 case reports were selected from 345 studies and data was extracted according to inclusion criteria. In all cases, NMOSD was reported following COVID-19 infection, and various symptoms such as blurring or loss of vision, weakness, and numbness were common, and the COVID-19 infection was confirmed by different tests such as PCR test, immunoglobulin assay and chest imaging. CONCLUSION: Review regarding case reports showed that NMOSD is conceivable following COVID-19.

Bilateral Acute Optic Perineuritis Associated With COVID-19 in a Patient With Seronegative Myelin Oligodendrocyte Glycoprotein (MOG) Antibody.

Severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) may cause various neuro-ophthalmologic manifestations including optic perineuritis. Optic perineuritis is a rare form of orbital inflammatory disease in which optic nerve sheath is inflamed and nonspecific fibrotic thickening with classic radiological finding is a perineural enhancement of optic nerve sheath. A 45-year-old gentleman with known diabetes mellitus, hypertension and dyslipidemia was admitted with a critically ill COVID-19 infection. During the recovery period, the patient developed sudden onset of painless loss of vision. MRI head and orbit with gadolinium was suggestive of optic perineuritis. Other secondary causes of autoimmune or vasculitis myelin oligodendrocyte glycoprotein (MOG) antibody disease and other common central nervous system (CNS) infection were excluded. The patient had dramatic response with steroids. This is the first rare case report of COVID-19-related optic perineuritis in critically ill COVID-19 patients with seronegative MOG antibody. Optic perineuritis is a rare orbital inflammatory disease and underlying mechanisms may arise from systemic response to COVID-19 infection as well as direct effects of the virus via angiotensin-converting enzyme 2 (ACE-2) receptors on ocular tissues. Optic perineuritis is a rare disease with inflammation restricted to the optic nerve sheath. Neuroimaging of the brain and orbit is the most important modality of choice for visualizing optic nerve sheath and optic nerve. Delay in the diagnosis of COVID-19-related optic perineuritis, may result in permanent optic nerve injury and irreversible vision loss.

COVID-19 susceptibility and outcomes among patients with neuromyelitis optica spectrum disorder (NMOSD): A systematic review and meta-analysis.

BACKGROUND: We conducted this systematic review and meta-analysis to assess the risk of coronavirus disease (COVID-19), clinical features and outcome among patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase from December 1, 2019, to July 2, 2021. The gray literature including the references of original studies, review studies, conference abstracts, and WHO COVID-19 database was also searched. We included any type of studies that reported NMOSD patients with COVID-19, prevalence of COVID-19 among NMOSD patients or the infection outcome (hospitalization, intensive care unit [ICU] admission, or mortality). RESULTS: Out of 540 records, a total of 23 studies (19 published articles and 4 conference abstracts) including 112 NMOSD patients with COVID-19 met the inclusion criteria. Nine studies reporting risk of COVID-19 and nine studies on outcome were included in a quantitative synthesis. The pooled prevalence of COVID-19 was 1.2% (95% CI: 0.001%-0.030%; I2 = 92%, p< 0.001), with hospitalization of 33.7% (95% CI: 23.3-44.8%; I2 = 9.1%, p = 0.360) with 52.9% on rituximab treatment. ICU admission was 15.4% (95% CI: 7.6%-24.7%; I2 = 20.7%, p = 0.272) and mortality was 3.3% (95% CI: 0-9.7%; I2 = 21.3%, p = 0.253). Thirty-eight patients (48.7%) reported at least one comorbidity. The mean age of the included patients was 40.8 (10.63) years, female/male ratio was 3.35:1. The most common COVID-19 symptom was fever (54.5%), followed by fatigue/asthenia (42.9%), headache (41.6%), and cough (40.3%). Four patients developed neurological worsening. The Begg's and Egger's tests showed no evidence of publication bias. CONCLUSION: The analysis suggests that comorbidity and treatment with rituximab may be risk factors for COVID-19 infection in NMOSD patients.

Post COVID-19 vaccination neuromyelitis optica spectrum disorder: Case report & MRI findings.

There are rising concerns among the medical community and the public regarding the side effects of different vaccines developed throughout the world and their short and long-term effects, particularly COVID19 vaccines. Most notably, post-vaccination demyelinating diseases such as acute disseminated encephalomyelitis, transverse myelitis, and multiple sclerosis relapses have been reported. We present a case of a 32-year-old male who presented with a 2 weeks history of acute confusional state and imbalance 1 week after receiving the second dose of COVID19 vaccination. MRI findings showed typical distribution of neuromyelitis optica spectrum disorder and the patient was positive for AQP4 IgG. The pathogenesis behind developing neuromyelitis optica and vaccines is still unknown. Few case reports have been reported of post-vaccination neuromyelitis optica spectrum disorder but to our knowledge, this would be the first case published of neuromyelitis optica following exposure to COVID19 vaccine.

Multiple sclerosis, neuromyelitis optica spectrum disorder and COVID-19: A pandemic year in Czechia.

BACKGROUND: When the novel coronavirus disease 2019 (COVID-19) appeared, concerns about its course in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) arose. This study aimed to evaluate the incidence, severity and risk factors of the more severe COVID-19 course among MS and NMOSD patients. METHODS: From March 1, 2020, to February 28, 2021, 12 MS centres, representing 70% of the Czech MS and NMOSD population, reported laboratory-confirmed COVID-19 cases via the Czech nationwide register of MS and NMOSD patients (ReMuS). The main outcome was COVID-19 severity assessed on an 8-point scale with a cut-off at 4 (radiologically confirmed pneumonia) according to the World Health Organisation´s (WHO) COVID-19 severity assessment. RESULTS: We identified 958 MS and 13 NMOSD patients, 50 MS and 4 NMOSD patients had pneumonia, 3 MS and 2 NMOSD patients died. The incidence of COVID-19 among patients with MS seems to be similar to the general Czech population. A multivariate logistic regression determined that higher body mass index (BMI [OR 1.07, 95% CI, 1.00-1.14]), older age (OR per 10 years 2.01, 95% CI, 1.41-2.91), high-dose glucocorticoid treatment during the 2 months before COVID-19 onset (OR 2.83, 95% CI, 0.10-7.48) and anti-CD20 therapy (OR 7.04, 95% CI, 3.10-15.87) were independent variables associated with pneumonia in MS patients. Increase odds of pneumonia in anti-CD20 treated MS patients compared to patients with other disease-modifying therapy (same age, sex, BMI, high-dose glucocorticoid treatment during the 2 months before COVID-19 onset, presence of pulmonary comorbidity) were confirmed by propensity score matching (OR 8.90, 95% CI, 3.04-33.24). Reports on COVID-19 infection in patients with NMOSD are scarce, however, data available up to now suggest a high risk of a more severe COVID-19 course as well as a higher mortality rate among NMOSD patients. In our cohort, 4 NMOSD patients (30.77%) had the more severe COVID-19 course and 2 patients (15.39%) died. CONCLUSION: The majority of MS patients had a mild COVID-19 course contrary to NMOSD patients, however, higher BMI and age, anti-CD20 therapy and high-dose glucocorticoid treatment during the 2 months before COVID-19 onset were associated with pneumonia. Based on this study, we have already started an early administration of anti-SARS-CoV-2 monoclonal antibodies and preferential vaccination in the risk group of patients.

COVID-19 and disease-modifying therapies in patients with demyelinating diseases of the central nervous system: A systematic review.

INTRODUCTION: The Coronavirus disease-19 (COVID-19) pandemic continues to expand across the world. This pandemic has had a significant impact on patients with chronic diseases. Among patients with demyelinating diseases of the central nervous system (CNS), such as Multiple Sclerosis (MS) or Neuromyelitis Optica Spectrum Disorder (NMOSD), concerns remain about the potential impact of COVID-19 on these patients given their treatment with immunosuppressive or immunomodulatory therapies. In this study, we review the existing literature investigating the impact of disease-modifying therapies(DMT) on COVID-19 risks in this group of patients. METHOD: For this systematic review, we searched PubMed from January 1, 2020, to December 3, 2020. The following keywords were used: "COVID-19" AND "Multiple Sclerosis" OR "Neuromyelitis Optica." Articles evaluating COVID-19 in patients with demyelinating diseases of CNS were included. This study evaluates the different aspects of the DMTs in these patients during the COVID-19 era. RESULTS AND CONCLUSION: A total of 262 articles were found. After eliminating duplicates and unrelated research papers, a total of 84 articles met the final inclusion criteria in our study. Overall, the experiences of 2493 MS patients and 37 NMOSD patients with COVID-19 were included in this review. Among them, 46(1.8%) MS patients died(the global death-to-case ratio of Covid-19 was reported about 2.1%). Among DMTs, Rituximab had the highest mortality rate (4%). Despite controversies, especially concerning anti-CD20 monoclonal antibody therapies, a relation between DMT-use and COVID-19 disease- course was not found in many studies. This observation reinforces the recommendation of not stopping current DMTs. Other variables such as age, higher expanded disability status scale (EDSS) scores, cardiac comorbidities, and obesity were independent risk factors for severe COVID-19. Despite the risks of infection, most patients were willing to continue their DMT during the pandemic because of more significant concern about the risk of relapse or worsening MS symptoms. After the infection, an immune response's attenuation was seen in the patients on Fingolimod and anti-CD20 monoclonal antibodies. This may be a critical finding in future vaccinations.