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The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic.

ABSTRACT: BACKGROUND:SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE:To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS:Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm and vascular pathology appears to contribute to the damage in ARDS. IMPLICATIONS:In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.

SUBMITTER: Baker D

PROVIDER: S-EPMC7214323 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic.

Baker David D Amor Sandra S Kang Angray S AS Schmierer Klaus K Giovannoni Gavin G

Multiple sclerosis and related disorders 20200512

<h4>Background</h4>SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS.<h4>Objective</h4>To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this imp ...[more]

PMID: 32464584

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Project description:BackgroundDisease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity and have the potential to increase the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and alter its clinical course. We assessed these risks in patients with MS (PwMS).ObjectiveThe objective of this study was to describe the overall risk of coronavirus disease 2019 (COVID-19) infection, severe disease course, and potential population-level predictors of COVID-19 infection in PwMS, and to provide a context using a cohort of patients with systemic lupus erythematosus (SLE). In addition, the association of different MS DMTs with the incidence and clinical course of COVID-19 was evaluated. Safety data from the Biogen Global Safety Database are also presented on reported cases of COVID-19 in patients treated with Biogen MS therapies.MethodsThe IBM® Explorys electronic health record database of > 72,000,000 patients from US healthcare networks identified patients with MS or SLE, with and without polymerase chain reaction-confirmed COVID-19. COVID-19 cumulative incidence, hospitalization, and deaths among DMT classes were compared using logistic regression (adjusted for age, sex, body mass index, comorbidities, and race/ethnicity). As a secondary data source to assess safety data, COVID-19 reports for Biogen MS therapies were extracted and described from Biogen's Global Safety Database.Results30,478 PwMS with an open DMT prescription were identified within Explorys; 344 were COVID-19 positive. The most significant risk factors for acquiring COVID-19 were comorbidity score ≥ 1, body mass index ≥ 30, and Black/African ancestry. Similar risk factors were also identified for patients with SLE. Patients with MS were less likely to develop COVID-19 when treated with interferons (0.61%) and glatiramer acetate (0.51%), vs all other MS DMTs (both p < 0.001); anti-CD20 therapy was associated with the highest risk (3.45%; p < 0.0001). In the Biogen Global Safety Database, we identified 1217 patients who were COVID-19 positive treated with intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel fumarate, or fampridine.ConclusionsComorbidities, obesity, and Black/African ancestry, but not age, were associated with a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were associated with a reduced COVID-19 risk, whereas anti-CD20 therapies were associated with an increased risk, within the treated MS cohort. COVID-19 safety reports for patients receiving Biogen MS therapies were consistent with the Explorys database and MS literature, illustrating the replicability and power of this approach.

Project description:The coronavirus 2019 (COVID-19) pandemic is expected to linger. Decisions regarding initiation or continuation of disease-modifying therapy for multiple sclerosis have to consider the potential relevance to the pandemic. Understanding the mechanism of action and the possible idiosyncratic effects of each therapeutic agent on the immune system is imperative during this special time. The infectious side-effect profile as well as the route and frequency of administration of each therapeutic agent should be carefully considered when selecting a new treatment or deciding on risk mitigation strategies for existing therapy. More importantly, the impact of each agent on the future severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) vaccine should be carefully considered in treatment decisions. Moreover, some multiple sclerosis therapies may have beneficial antiviral effects against SARS-CoV-2 while others may have beneficial immune-modulating effects against the cytokine storm and hyperinflammatory phase of the disease. Conventional injectables have a favorable immune profile without an increased exposure risk and therefore may be suitable for mild multiple sclerosis during the pandemic. However, moderate and highly active multiple sclerosis will continue to require treatment with oral or intravenous high-potency agents but a number of risk mitigation strategies may have to be implemented. Immune-modulating therapies such as the fumerates, sphinogosine-1P modulators, and natalizumab may be anecdotally preferred over cell-depleting immunosuppressants during the pandemic from the immune profile standpoint. Within the cell-depleting agents, selective (ocrelizumab) or preferential (cladribine) depletion of B cells may be relatively safer than non-selective depletion of lymphocytes and innate immune cells (alemtuzumab). Patients who develop severe iatrogenic or idiosyncratic lymphopenia should be advised to maintain social distancing even in areas where lockdown has been removed or ameliorated. Patients with iatrogenic hypogammaglobulinemia may require prophylactic intravenous immunoglobulin therapy in certain situations. When the future SARS-CoV-2 vaccine becomes available, patients with multiple sclerosis should be advised that certain therapies may interfere with mounting a protective immune response to the vaccine and that serological confirmation of a response may be required after vaccination. They should also be aware that most multiple sclerosis therapies are incompatible with live vaccines if a live SARS-CoV-2 vaccine is developed. In this article, we review and compare disease-modifying therapies in terms of their effect on the immune system, published infection rates, potential impact on SARS-CoV-2 susceptibility, and vaccine-related implications. We propose risk mitigation strategies and practical approaches to disease-modifying therapy during the COVID-19 pandemic.

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in late 2019 and Covid-19, a disease caused by SARS-CoV-2 became a pandemic in March 2020. As the pandemic still unfolds, uncertainty circles around the impact of SARS-CoV-2 infection on patients with chronic diseases, including autoimmune diseases such as multiple sclerosis (MS). To diminish the risk of SARS-CoV-2 infection and lessen the impact of the Covid-19 pandemic on the healthcare of MS patients, it is essential to understand knowledge, attitudes, and various behavioral practices related to Covid-19 among MS patients. Therefore, this study aimed to look at the behavioral practices related to Covid-19 among patients with MS. A total of 176 MS patients diagnosed at least one year before the survey were conveniently sampled online in Saudi Arabia and their data collected using a structured interview questionnaire in electronic Google form. We determined the reliability of the questionnaire by measuring its internal consistency in a pilot sample of 30 participants. Overall, more than 80% of participants had good knowledge and attitudes towards Covid-19. However, this did not correlate well with the impact on healthcare (r = 0.06). Our study revealed that 46% of participants were anxious about taking their medication, and 32% of participants missed their hospital appointments. Furthermore, 15% of the participants had a relapse but did not go to the hospital because of the pandemic, 15.9% stopped their DMTs, and 35.2% missed drug infusions or refills. Our study revealed overall good knowledge and attitudes related to Covid-19 among MS patients. However, the healthcare impact was considerable, as 32% of the participants missed their hospital appointments, and another 15% had a relapse. This highlights the significance of the impact of the Covid-19 pandemic on the healthcare of patients with MS. Measures to mitigate the effect of the pandemic on healthcare service delivery to patients with MS, such as telemedicine, should be strongly encouraged.

Project description:Objective: The coronavirus disease 2019 (COVID-19) has radically changed the world in a few weeks. Italy has been one of the first and most affected countries with more than 30,000 deaths up to now. Public health measures as quarantine or national lockdown are necessary to limit the spread of infectious diseases, but it is unsurprising that depriving people of their liberty has negative psychological effects. This is especially the case for people with chronic diseases, including neurological conditions like multiple sclerosis (MS). People with MS (PwMS) have a higher burden of neuropsychiatric comorbidities and are known to undertake maladaptive coping strategies in stress conditions. The aim of the present study is to investigate the impact of COVID-19 pandemic lockdown on mental health of an Italian cohort of PwMS in comparison with healthy controls (HCs). Methods: A total of 60 PwMS and 50 HCs (chosen among patients' cohabitants) were asked to answer a Web-based survey. This survey inquired about the impact of COVID-19 on patient's quality of life, job, and daily routine. Mood, fatigue, and sleep quality were evaluated using the Beck Depression Inventory II (BDI-II), the Generalized Anxiety Disease 7 (GAD-7), the Fatigue Severity Scale (FSS), and the Pittsburgh Sleep Quality Index (PSQI). Results: Overall, patients had higher scores of BDI, FSS, and PSQI, and these differences were statistically significant (p < 0.05). When we looked at the subscores of the BDI, we detected a statistically significant difference for the neurovegetative part-that concerns with sleep, appetite, sex, and quality of sleep (p < 0.05). One out of five patients reported new symptoms or worsening of known symptom, in particular, sensory disturbances, and fatigue. However, no symptoms were severe enough to require hospitalization. When we looked for correlations among variables, we found that there was a significant relationship between unemployment and BDI total score, GAD-7, and PSQI in MS group. The presence of new symptoms or the worsening of symptoms positively related to FSS and to PSQI. Discussion: We identified that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had a significant impact on the psychological status of patients with MS. Compared with the general population, PwMS presented a higher burden of depressive symptoms, a worse sleep quality and perceived an increase in fatigue level, one of the most disabling symptoms of MS. The COVID-19 epidemic poses a challenge to psychological resilience. More studies are warranted to better understand the long-term consequences of the pandemic on mental health of vulnerable people during the disease outbreaks.

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The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic.

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The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic.

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