Safety and Monitoring of the treatment with Disease-Modifying Therapies for Multiple Sclerosis.

BACKGROUND: Disease-Modifying Therapies (DMTs) for Multiple Sclerosis (MS) are widely used given their proven efficacy in the relapsing form of the disease, while recently Siponimod and Ocrelizumab have been approved for the progressive forms of the disease. Currently, 22 Disease-modifying drugs are approved by the FDA, while in 2012, only nine were in the market. From March 2019 until August 2020, six new drugs were approved. This rapid development of new DMTs highlights the need to update our knowledge about their short and long-term safety. OBJECTIVE: This review summarizes the available safety data for all the Disease-Modifying Therapies for Multiple Sclerosis and presents the monitoring plan before and during the treatment. METHODS: A literature search was conducted in PUBMED and COCHRANE databases. Also, we manually searched key journals and abstracts from major annual meetings of Neurology, references of relevant reviews, and relative articles. We prioritized systematic reviews, large randomized controlled trials (RCTs), prospective cohort studies, and other observational studies. Special attention was paid to guidelines and papers focusing on the safety and monitoring of DMTs. Data for oral (Sphingosine 1-phosphate (S1P) receptor modulators, Fumarates, Teriflunomide, Cladribine), injectables (Interferons, Glatiramer acetate, Ofatumumab), and infusion therapies (Natalizumab, Ocrelizumab, Alemtuzumab) are presented.

Spike Ab seroconversion following SARS-CoV-2 vaccination in Australian people with Multiple Sclerosis

Background: SARS-CoV-2 antibody responses after COVID-19 vaccination are attenuated in people living with MS on high efficacy DMTs such as Fingolimod and Ocrelizumab. Uncertainties on how to manage vaccination schedule and DMT administration persist. Furthermore, data on effects of newer related DMTs like Siponimod and Ofatumumab are limited. Objective(s): We aimed to determine the seroprevalance of Spike antibody and the longevity of antibody mediatedimmune protection after COVID-19 vaccination in MS patients. Method(s): Spike IgG antibodies against Wuhan SARS CoV-2 were assessed in sera (n=520) of MS patients collected pre-vaccination (baseline n= 304), 1 month post second dose (n=172), 6 months post second dose (n=23) and 1 month post third dose (n=21). Demographic and clinical information including age, gender, DMT treatment and timing of COVID-19 vaccination were collected from 160 of these MS patients. Result(s): 151/172 sera at 1 month post second dose, 20/23 sera at 6 months post second dose, and 15/21 sera at 1 month post third dose were positive for Spike antibodies. Seropositive patients were treated on Alemtuzumab;n=3, Cladribine;n=32, Dimethyl fumarate;n=8, Fingolimod;n=16, IFN;n =4, Ocrelizumab;n=14, Ofatumumab;n=4, Natalizumab;n=11, Siponimod;n=1 and Teriflunomide;n=1. Out of the 21 patients who did not seroconvert at a month post second dose, treatment information was available in 12 patients. n=9 were treated by Ocrelizumab and n=2 were treated by Cladribine and n=1 was treated by Fingolimod, confirming certain DMTs prevent seroconversion. Out of the 151 patients that did seroconvert, 120 had titers that were comparable to controls (healthy general population) and 31 had reduced titres. Treatment information was available in 21/31 of these patients. Interestingly, 9/21 were on Ocrelizumab, 8/21 were on Fingolimod, 2/21 were on Ofatumumab, 1/21 was on Natalizumab and 1/21 was on Siponimod. This finding confirmed that certain DMTs such as Fingolimod, Ocrelizumab, Ofatumumab and Siponimod cause a reduction in post-vaccination Spike antibody titers in MS patients in comparison to general population. Expectedly, 304/304 sera were negative at baseline. Conclusion(s): Some High efficacy DMTs reduce Spike Ab titers or even prevent seroconversion. To maximize vaccine-mediated immune protection against COVID-19, timing of DMT administration and vaccine schedule may need intricate co-ordination in people living with MS.

IRON METABOLISM DISORDERS AND THEIR PHARMACOLOGICAL CORRECTION

The main pathological conditions characterized by disturbances of iron metabolism have been analyzed, including anemias, hemochromatosis, inflammatory, autoimmune and neurodegenerative disorders, chronic renal insufficiency, infectious diseases (including COVID-19), etc. Strategies of their pharmacological correction and risks of common adverse effects development are considered for the potential targets of pharmacotherapy and possible groups of medications including inhibitors of prolyl-4-hydroxylase, inhibitors of bone morphogenetic proteins (BMP 6), ferroportin and hepcidin activity, inhibitors of hypoxia-inducible factor (HIF-1a) and divalent metal transporter (DMT-1). Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

Immune responses following COVID-19 infection in multiple sclerosis patients using immunomodulatory therapy.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has quickly become a global pandemic. Most multiple sclerosis (MS) patients use disease-modifying treatments (DMTs), such as immunomodulators or immunosuppressants. By targeting different types of immune cells, DMTs affect cellular and/or humoral immunity. The potential effects of DMTs on the long-term immune response to COVID-19 is not fully known. Between 16.04.2020 and 15.07.2020, a total of 34 people, 17 of whom were diagnosed with MS according to the 2010 McDonald diagnostic criteria and a control group of 17 individuals who did not have a known systemic disease who were matched according to age, gender, and COVID-19 disease severity, where all received COVID-19 diagnosis with SARS-CoV-2 PCR positivity in nasopharyngeal swab test and immune responses were measured (SARS-CoV-2 IgM and IgG antibody levels COVID 19 ELISA kit), were included in our study. Demographic data of MS patients and the control group, SARS-CoV-2 immune responses, antibody titers and disease year of MS patients, EDSS scores, disease type, and disease duration were determined. All patients were symptomatic for COVID-19. COVID-19 disease severity was divided into three groups as mild, moderate, and severe according to the clinical condition of the patient. Demographic data of MS patients and the control group, SARS-CoV-2 immune responses, antibody titers and disease year of MS patients, EDSS scores, disease type, and disease duration were determined. All patients were symptomatic for COVID-19. COVID-19 disease severity was divided into three groups as mild, moderate, and severe according to the clinical condition of the patient. According to our study results, IgG-type long-term immune responses were lower in MS patients using DMTs than in the healthy population. We hope that our study will provide insight into the COVID-19 vaccine immune responses.

Cross-sectional analysis of the humoral response after SARS-CoV-2 vaccination in Sardinian multiple sclerosis patients, a follow-up study.

Monitoring immune responses to SARS-CoV-2 vaccination and its clinical efficacy over time in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs) help to establish the optimal strategies to ensure adequate COVID-19 protection without compromising disease control offered by DMTs. Following our previous observations on the humoral response one month after two doses of BNT162b2 vaccine (T1) in MS patients differently treated, here we present a cross-sectional and longitudinal follow-up analysis six months following vaccination (T2, n=662) and one month following the first booster (T3, n=185). Consistent with results at T1, humoral responses were decreased in MS patients treated with fingolimod and anti-CD20 therapies compared with untreated patients also at the time points considered here (T2 and T3). Interestingly, a strong upregulation one month after the booster was observed in patients under every DMTs analyzed, including those treated with fingolimod and anti-CD20 therapies. Although patients taking these latter therapies had a higher rate of COVID-19 infection five months after the first booster, only mild symptoms that did not require hospitalization were reported for all the DMTs analyzed here. Based on these findings we anticipate that additional vaccine booster shots will likely further improve immune responses and COVID-19 protection in MS patients treated with any DMT.

Biopolymeric sustainable materials and their emerging applications

Advancements in polymer science and engineering have helped the scientific community to shift its attention towards the use of environmentally benign materials for reducing the environmental impact of conventional synthetic plastics. Biopolymers are environmentally benign, chemically versatile, sustainable, biocompatible, biodegradable, inherently functional, and ecofriendly materials that exhibit tremendous potential for a wide range of applications including food, electronics, agriculture, textile, biomedical, and cosmetics. This review also inspires the researchers toward more consumption of biopolymer-based composite materials as an alternative to synthetic composite materials. Herein, an overview of the latest knowledge of different natural- and synthetic-based biodegradable polymers and their fiber-reinforced composites is presented. The review discusses different degradation mechanisms of biopolymer-based composites as well as their sustainability aspects. This review also elucidates current challenges, future opportunities, and emerging applications of biopolymeric sustainable composites in numerous engineering fields. Finally, this review proposes biopolymeric sustainable materials as a propitious solution to the contemporary environmental crisis. © 2022 Elsevier Ltd.

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.

Seroprevalence of SARS-CoV-2 in a Cohort of Patients with Multiple Sclerosis under Disease-Modifying Therapies.

BACKGROUND: Disease-modifying therapies (DMTs) used to treat multiple sclerosis (MS) alter the immune system and therefore increase the risk of infection. There is growing concern about the impact of COVID-19 on patients with MS (pwMS), especially those treated with DMTs. METHODS: This is a single-center prospective observational study based on data from the Esclerosis Múltiple y COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data and SARS-CoV-2 serology, and symptoms of COVID-19 in pwMS treated with any DTM were extracted. The relationship among demographics, MS status, DMT, and COVID-19 was evaluated. RESULTS: A total of 259 pwMS were included. The administration of interferon was significantly associated with the presence of SARS-CoV-2 antibodies (26.4% vs. 10.7%, p = 0.006). Although patients taking interferon were significantly older (49.1 vs. 43.5, p = 0.003), the association of interferon with the presence of SARS-CoV-2 antibodies was still significant in the multivariate analysis (OR 2.99 (1.38; 6.36), p = 0.006). CONCLUSIONS: According to our data, pwMS present a higher risk of COVID-19 infection compared with results obtained from the general population. There is no evidence of a worse COVID-19 outcome in pwMS. DMTs did not significantly change the frequency of COVID-19, except for interferon; however, these findings must be interpreted with caution given the small sample of pwMS taking each DMT.

COVID-19 Vaccination in Multiple Sclerosis and Inflammatory Diseases: Effects from Disease-Modifying Therapy, Long-Term Seroprevalence and Breakthrough Infections.

BACKGROUND: To determine the effect of disease-modifying therapies (DMT) on humoral postvaccine seroconversion, long-term humoral response, and breakthrough COVID-19 infections in persons with multiple sclerosis (PwMS) and other neuroinflammatory disorders. METHODS: A total of 757 PwMS and other neuroinflammatory disorders were recruited in two MS centers and vaccinated with one of the FDA-approved vaccines (BNT162b2, mRNA-1273, Ad26.COV2.S). The primary outcomes are the rate of humoral postvaccine seroconversion and anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) immunoglobulin G (IgG) differences between patients on different DMTs. Secondary measures include breakthrough infections and humoral response after six months. Other outcomes include differences in vaccine response between SARS-CoV-2 vaccines and the effects of age and comorbidities on the vaccine response. RESULTS: A total of 465 (68.4%) PwMS and 55 (74.3%) patients with neuroinflammatory diseases were seropositive at 4-12 weeks after vaccination. A significant difference in seroconversion based on the DMT used at the time of vaccination (p < 0.001) was observed, with the lowest rates seen in patients treated with anti-CD20 antibodies (23.2%) and sphingosine-1-phosphate modulators (S1P) (30.8%). In seropositive patients, there was a significant decrease in anti-SARS IgG from mean 20.0 to 4.7 at six months (p = 0.004). Thirty-nine patients had breakthrough infection, but only two seronegative patients required hospitalization. mRNA vaccines resulted in significantly greater seroconversion compared to Ad26.COV2.S (p < 0.001). Older age and presence of cardiovascular comorbidities were associated with lower anti-SARS IgG (p = 0.021 and p = 0.003, respectively) Conclusions: PwMS and neuroinflammatory disorders treated with anti-CD20 and S1P medications have lower humoral response after anti-SARS-CoV-2 vaccination, even after booster dose. Waning of the humoral response puts vaccinated PwMS at a greater risk of COVID-19 breakthrough.

The humoral response to SARS-COV-2 vaccines in MS patients: A case series exploring the impact of DMT, lymphocyte count, immunoglobulins, and vaccine type.

BACKGROUND & OBJECTIVES: Certain disease modifying therapies may negatively impact the humoral response to SARS-CoV-2 vaccines. Many MS related clinical, demographic, and immunological characteristics can also affect vaccine response but those have not been fully explored. This study aimed to investigate potential correlations between clinical, demographic, and immunological variables in MS patients to post-vaccination spike protein antibody positivity rates and levels. METHODS: Patients with MS and related neuroimmunological disorders who requested verification of the immune response to the SARS-COV-2 vaccine were tested for the spike protein antibody from January to October 2021. We performed an exploratory analysis to compare patients with positive versus negative spike protein antibody. RESULTS: Fifty patients (mean age 53 ±12, 78% females) were included. There were 29 patients with positive post-vaccination spike protein antibody (58%) and 21 with negative antibody (42%). Patients with negative antibody were more likely to have been on B-cell therapy (86% vs 31%, P=.001) while positive patients were more likely to have been on a fumarate (31% vs 4.8%, P=.03). Thirty percent of positive patients on fumarate therapy had mild lymphopenia. No differences existed between groups in gender, age, race, disease phenotype, vaccine brand, and lymphocyte counts. Among patients on B-cell therapy, 33% had a positive spike protein antibody. There was an association between detectable CD19 cells at time of vaccination and positive humoral response to vaccination (P=0.049). There was no relationship between subgroups in terms of vaccine timing relative to B-cell therapy dose. Hypogammaglobulinemia was not associated with seroconversion rates, however it was associated with decreased quantitative spike protein antibody levels (p=0.045). DISCUSSION: B-cell therapy is associated with a negative humoral response to SARS-COV-2 vaccines. Patients on B-cell depleting therapy with detectable CD19 counts at the time of vaccination were associated with a positive humoral response. There was no relationship between hypogammaglobinemia and seroconversion rate, however it was associated with decreased spike protein antibody levels. The fumarates are associated with positive humoral response even in the presence of mild lymphopenia.

Prescription trends of disease-modifying treatments for multiple sclerosis in Iran over the past 30 years.

BACKGROUND: Iran, as a middle income country, is one of the places with high and rising prevalence of multiple sclerosis (MS). Regarding the substantial economic burden, reviewing the trend in prescribed disease modifying treatments (DMTs) could be of help. Here we studied the DMT information of nearly 14000 MS cases and its trends change for 30 years to improve health services to patients. METHODS: The population base of this descriptive-analytical (cross-sectional) study consisted of all MS patients in the nationwide MS registry of Iran (NMSRI), up to August 1, 2021. Registrars from 15 provinces, 24 cities, 13 hospitals,8 MS associations, 16 private offices, and 7 clinics had entered the data. RESULTS: Overall, 14316 cases were enrolled. The majority (76.1%) were female. The youngest and eldest patients were 5 and 78 years old, respectively. Diagnosis delay was under one year in most cases (median: 0, IQR: 0 - 1). Most (61.4%) had RRMS. Generally, platform injectables (IFN beta, glatiramer acetate) were the most used DMTs until 2010. It seems that introduction of newer agents (antiCD20s and oral DMTs) resulted in a decrease in the use of former drugs since around 2015. Some unusual practices are prominent such as using not approved DMTs for PPMS over the years, or administering high efficacy drugs like natalizumab for CIS. The results indicate the remaining popularity of first line injectable DMTs in female and pediatric patients. DISCUSSION: Mean age (SD) at onset in our study (29 ± 8.8) is near the statistics in Asia and Oceania (28 ± 0.7). Concerns about COVID-19 had a noticeable impact on administering high efficacy drugs like rituximab and fingolimod. However, in male patients this approach has not been the case. It may be related to more aggressive disease course in this group. The other possible explanation could be planning for pregnancy in female cases. The popularity of platform injectable drugs in pediatric MS may be related to its favorable safety profile over the years. Another point in this group, is the superiority of rituximab over other highly efficient medications.

Immunology of COVID-19 and disease-modifying therapies: The good, the bad and the unknown.

OBJECTIVE: The outbreak of the SARS-CoV-2 pandemic, caused by a previously unknown infectious agent, posed unprecedented challenges to healthcare systems and unmasked their vulnerability and limitations worldwide. Patients with long-term immunomodulatory/suppressive therapies, as well as their physicians, were and are concerned about balancing the risk of infection and effects of disease-modifying therapy. Over the last few months, knowledge regarding SARS-CoV-2 has been growing tremendously, and the first experiences of infections in patients with multiple sclerosis (MS) have been reported. METHODS: This review summarizes the currently still limited knowledge about SARS-CoV-2 immunology and the commonly agreed modes of action of approved drugs in immune-mediated diseases of the central nervous system (MS and neuromyelitis optica spectrum disorder). Specifically, we discuss whether immunosuppressive/immunomodulatory drugs may increase the risk of SARS-CoV-2 infection and, conversely, may decrease the severity of a COVID-19 disease course. RESULTS: At present, it can be recommended in general that none of those therapies with a definite indication needs to be stopped per se. A possibly increased risk of infection for most medications is accompanied by the possibility to reduce the severity of COVID-19. CONCLUSIONS: Despite the knowledge gain over the last few months, current evidence remains limited, and, thus, further clinical vigilance and systematic documentation is essential.

Multiple sclerosis patients and COVID-19.

Coronavirus disease 2019 (COVID-19) is now a major issue for all fields of medicine. Due to the higher mortality rate among patients with chronic diseases, it has also caused concern in patients with multiple sclerosis (MS), who in addition are often receiving immunosuppressive drugs. The aim of this article is to discuss what is currently known about the severity of COVID-19 in MS patients.

The effect of the Safer at Home order on the frequency of DUI breath alcohol tests in Los Angeles County.

With Los Angeles County having a population size of just over 10 million and an additional 471,000 people who commute into Los Angeles County for employment, many drivers are at risk of being injured or killed in an alcohol-impaired driving collision. On March 19, 2020, the County of Los Angeles issued the Safer at Home order as a result of the COVID-19 pandemic. This curtailed driving and decreased the number of breath alcohol tests that were conducted in Los Angeles County. The number of breath tests conducted in January-February of 2019 and 2020 and March-April of 2019 and 2020 were evaluated using Fisher's exact test and analysis of variance. There was a statistically significant decrease in the overall number of breath tests conducted in Los Angeles County in March-April of 2020. There was also a significant decrease in the number of collisions where DUI was a factor. Accounting for changes in traffic volumes, the number of breath tests per vehicle miles driven also decreased significantly. Since the Safer at Home order closed all non-essential services such as bars and restaurants, there is indirect data on the relative contribution of liquor-serving establishments, and to some extent large social gatherings, to the incidence of drunk driving. Taking into account traffic volume, it was determined that the odds of encountering an intoxicated driver decreased by approximately 23% during the Safer at Home period. This information could help policy-makers determine the likely effectiveness of various countermeasures to prevent drunk driving.

Safety of disease-modifying treatments in SARS-CoV-2 antibody-positive multiple sclerosis patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) raises particular concerns for people with multiple sclerosis (PwMS) on disease-modifying treatments (DMTs), and for physicians caring for them. The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on PwMS receiving DMTs that inhibit immune cell trafficking, such as natalizumab (NTZ) and fingolimod (FTY), remains to be determined, as do the possible effects of these drugs on both the infection and the related disease. AIMS: To describe self-reported COVID-19 symptoms and disease severity in PwMS on NTZ or FTY who received serology confirmation of SARS-CoV-2 infection. METHODS: From 27th April to 3rd May 2020, telephone interviews were conducted with 140 PwMS under treatment with NTZ or FTY in order to collect structured data on multiple sclerosis (MS) and COVID-19. The patients, all followed at our center, were classified as symptomatic, paucisymptomatic or asymptomatic on the basis of their self-reported clinical characteristics. COVID-19 severity was rated on a 7-point ordinal scale. In addition, in the period 4th May to 3rd June 2020 SARS-CoV-2 serology testing, using the Roche SARS-CoV-2 IgG assay (ElecsysⓇ), was performed in 104/140 (74.2%) of the interviewed PwMS (50 treated with NTZ and 54 with FTY). RESULTS: 14/104 (13.4%) PwMS on NTZ or FTY had anti-SARS-CoV-2 antibodies: 8 met the criteria for asymptomatic, 3 for paucisymptomatic and 3 for symptomatic COVID-19 (COVID-19 severity score lower than 3). None of them required hospitalization or showed severe COVID-19 complications. CONCLUSIONS: Despite the relatively high SARS CoV-2 seroprevalence found in this sample of PwMS, all the positive cases showed either no or only mild COVID-19 symptoms. These reassuring findings indicate a lack of COVID-19 complications in PwMS on DMTs and support the hypothesis that it is safe to maintain ongoing treatment with these drugs in the current setting.

A case series and literature review of multiple sclerosis and COVID-19: Clinical characteristics, outcomes and a brief review of immunotherapies.

BACKGROUND: In view of the emerging coronavirus pandemic, the demand for knowledge about the impact of SARS-CoV-2 on people with Multiple Sclerosis (MS) continues to grow. Patients receiving disease modifying therapy (DMT) for MS have a higher background risk of infection-related health care utilization when compared to the general population. Therefore, there is a need of evidence-based recommendations to reduce the risk of infection and also managing MS patients with SARS-CoV-2. CASE DESCRIPTION: We present three patients with history of Multiple Sclerosis (MS) on DMTs presenting with worsening MS symptoms likely pseudo exacerbation who were diagnosed with COVID-19. DISCUSSION: An extensive review of 7 articles was performed, in addition to a brief review on DMTs use in MS patients with COVID-19. In our cases, all patients were on DMT and severe course of disease was noted in 2 cases. No fatality was observed. CONCLUSIONS: This review provides a base on the clinical characteristics, outcomes and the roles of DMTs in MS patients suffering from n-cov-2. Physicians need to be vigilant about considering COVID-19 infection related relapse in the MS patients, especially in this COVID-19 pandemic era and look for pseudo-exacerbation. As most cases are found to have mild course and full recovery on DMTs, further research is needed to formulate evidence-based guidelines. This review will particularly be helpful for the researchers and registries to collect future data on MS and COVID-19.

Effects of Antimalarial Drugs on Neuroinflammation-Potential Use for Treatment of COVID-19-Related Neurologic Complications.

The SARS-CoV-2 virus that is the cause of coronavirus disease 2019 (COVID-19) affects not only peripheral organs such as the lungs and blood vessels, but also the central nervous system (CNS)-as seen by effects on smell, taste, seizures, stroke, neuropathological findings and possibly, loss of control of respiration resulting in silent hypoxemia. COVID-19 induces an inflammatory response and, in severe cases, a cytokine storm that can damage the CNS. Antimalarials have unique properties that distinguish them from other anti-inflammatory drugs. (A) They are very lipophilic, which enhances their ability to cross the blood-brain barrier (BBB). Hence, they have the potential to act not only in the periphery but also in the CNS, and could be a useful addition to our limited armamentarium against the SARS-CoV-2 virus. (B) They are non-selective inhibitors of phospholipase A2 isoforms, including cytosolic phospholipase A2 (cPLA2). The latter is not only activated by cytokines but itself generates arachidonic acid, which is metabolized by cyclooxygenase (COX) to pro-inflammatory eicosanoids. Free radicals are produced in this process, which can lead to oxidative damage to the CNS. There are at least 4 ways that antimalarials could be useful in combating COVID-19. (1) They inhibit PLA2. (2) They are basic molecules capable of affecting the pH of lysosomes and inhibiting the activity of lysosomal enzymes. (3) They may affect the expression and Fe2+/H+ symporter activity of iron transporters such as divalent metal transporter 1 (DMT1), hence reducing iron accumulation in tissues and iron-catalysed free radical formation. (4) They could affect viral replication. The latter may be related to their effect on inhibition of PLA2 isoforms. Inhibition of cPLA2 impairs an early step of coronavirus replication in cell culture. In addition, a secretory PLA2 (sPLA2) isoform, PLA2G2D, has been shown to be essential for the lethality of SARS-CoV in mice. It is important to take note of what ongoing clinical trials on chloroquine and hydroxychloroquine can eventually tell us about the use of antimalarials and other anti-inflammatory agents, not only for the treatment of COVID-19, but also for neurovascular disorders such as stroke and vascular dementia.

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.

Mild clinical manifestations of SARS-CoV-2 related pneumonia in two patients with multiple sclerosis under treatment with ocrelizumab.

BACKGROUND: Recently SARS-CoV-2 has spread worldwide causing a pandemic. Little is known about disease severity in immunocompromised hosts and people receiving disease modifying therapies (DMTs). In the last decades DMTs have been widely employed, and ocrelizumab represents one of the newest therapies for the relapsing remitting and progressive forms of multiple sclerosis (MS). OBJECTIVES: to describe SARS-CoV-2 related pneumonia in two MS patients under ocrelizumab treatment. METHODS: Case series. RESULTS: Patients showed a mild clinical course of SARS-CoV-2 related pneumonia without complications or sequelae. CONCLUSION: Ocrelizumab treatment is not necessarily associated to increased severity in MS patients with SARS-CoV-2 infection.