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1.
Mult Scler Relat Disord ; 63: 103921, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-2181738

ABSTRACT

BACKGROUND: Infections in people with multiple sclerosis (PwMS) may have a detrimental effect on disease progression, risk of hospitalization, and healthcare resource utilization (HRU). The infection risk and HRU costs may vary between disease-modifying therapies (DMTs); however, the individual risks and differences associated with DMTs are not well characterized. Some DMTs may increase the risk for infections in PwMS; however, previous studies have reported an intact humoral immune response in dimethyl fumarate (DMF)-treated patients. The objective was to compare infection-related HRU and healthcare costs (HCCs) between PwMS treated with DMF or ocrelizumab (OCR). METHODS: Eligible patients were identified from the Optum US claims database between April 2017 and September 2020 (DMF n = 1429; OCR n = 3170). Patients were followed from index date to first occurrence of: (1) end of study, (2) end of insurance eligibility, (3) discontinuation of index DMT, or (4) switch from index DMT to another DMT. Outcomes were annualized rate of infection encounters (defined as infection encounters [n] during follow-up window / days followed [n] × 365); annualized infection-related HCCs (defined as aggregated costs of infection encounters during follow-up window / days followed [n] × 365); location-specific infections, and overall infection-related events. Propensity score matching (PSM) 1:1 method was used; PS was calculated via logistic regression for probability of DMF treatment conditional on demographics and comorbidities. Mean differences (MD) were reported for infection encounter measures. RESULTS: After PSM, DMF and OCR cohorts (n = 1094 in each cohort) were balanced based on baseline characteristics (standardized MD of adjusted baseline characteristics <0.1). Mean (standard deviation) follow-up was 296 (244) days for DMF patients and 297 (243) for OCR patients. DMF patients experienced lower annualized rates of overall infection encounters vs OCR patients (MD -0.51 [95% confidence interval (CI): -0.92 to -0.11], p = 0.01). When stratified by type of infection encounter, DMF patients experienced significantly lower annualized rates of outpatient (MD [95% CI]: -0.44 [-0.80 to -0.08], p = 0.02) and inpatient/hospitalization infection encounters (-0.08 [-0.14 to -0.02], p<0.01) vs OCR patients. A trend towards a shorter duration of infection-related hospitalization in the DMF vs the OCR group was observed (MD [95% CI]: -2.20 [-4.73 to 0.26] days, p = 0.08). The most common infection types in both DMT groups were urinary tract infections, sepsis, and pneumonia. DMF patients experienced lower annualized infection-related HCCs (MD [95% CI]: -$3642 [-$6380 to -$904], p < 0.01) vs OCR patients, which were driven largely by infection-related hospitalization costs (-$3639 [-$6019 to -$1259], p < 0.01). CONCLUSION: DMF-treated patients PS-matched with OCR patients experienced lower annualized rates of infection encounters and lower infection-related HCCs.


Subject(s)
Dimethyl Fumarate , Multiple Sclerosis , Antibodies, Monoclonal, Humanized/adverse effects , Dimethyl Fumarate/therapeutic use , Health Care Costs , Humans , Multiple Sclerosis/chemically induced , Multiple Sclerosis/complications , Multiple Sclerosis/drug therapy , Retrospective Studies
2.
Mult Scler Relat Disord ; 66: 104072, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2015867

ABSTRACT

BACKGROUND: Interferon-ß, a disease-modifying therapy (DMT) for MS, may be associated with less severe COVID-19 in people with MS. RESULTS: Among 5,568 patients (83.4% confirmed COVID-19), interferon-treated patients had lower risk of severe COVID-19 compared to untreated, but not to glatiramer-acetate, dimethyl-fumarate, or pooled other DMTs. CONCLUSIONS: In comparison to other DMTs, we did not find evidence of protective effects of interferon-ß on the severity of COVID-19, though compared to the untreated, the course of COVID19 was milder among those on interferon-ß. This study does not support the use of interferon-ß as a treatment to reduce COVID-19 severity in MS.


Subject(s)
COVID-19 , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Acetates , Dimethyl Fumarate/therapeutic use , Glatiramer Acetate/therapeutic use , Humans , Immunosuppressive Agents/adverse effects , Interferon-beta/therapeutic use , Multiple Sclerosis/chemically induced , Multiple Sclerosis/complications , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Relapsing-Remitting/chemically induced
3.
Mult Scler Relat Disord ; 62: 103800, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1783664

ABSTRACT

BACKGROUND & OBJECTIVES: The persistence of the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Here, we present data regarding the decline of the SARS-CoV-2 BNT162b2 mRNA vaccine-induced humoral immune response in a monocentric cohort of MS patients. METHODS: 96 MS patients undergoing eight different DMTs, all without previous SARS-CoV-2 infection, were evaluated for anti-Spike IgG levels, 21 days (T1) and 5-6 months (T2) after the second SARS-CoV-2 BNT162b2 mRNA vaccine dose. The anti-Spike IgG titre from MS subjects was compared with 21 age- and sex-matched healthy controls (HC). RESULTS: When compared with SARS-CoV-2 IgG levels at T2 in HC, we observed comparable levels in interferon-ß 1a-, dimethyl fumarate-, teriflunomide- and natalizumab-treated MS subjects, but an impaired humoral response in MS subjects undergoing glatiramer acetate-, cladribine-, fingolimod- and ocrelizumab-treatments. Moreover, comparison between SARS-CoV-2 IgG Spike titre at T1 and T2 revealed a faster decline of the humoral response in patients undergoing dimethyl fumarate-, interferon-ß 1a- and glatiramer acetate-therapies, while those receiving teriflunomide and natalizumab showed higher persistence compared to healthy controls. CONCLUSION: The prominent decline in humoral response in MS subjects undergoing dimethyl fumarate-, interferon-ß 1a- and glatiramer acetate-therapies should be considered when formulating booster regimens as these subjects would benefit of early booster vaccinations.


Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Viral , COVID-19 Vaccines , Dimethyl Fumarate/therapeutic use , Glatiramer Acetate/therapeutic use , Humans , Immunoglobulin G/therapeutic use , Interferon beta-1a/therapeutic use , Multiple Sclerosis/drug therapy , Natalizumab/therapeutic use , SARS-CoV-2 , Vaccines, Synthetic
4.
Mult Scler Relat Disord ; 60: 103735, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1734831

ABSTRACT

BACKGROUND: The risk of SARS-CoV-2 infection and severity with disease modifying therapies (DMTs) in multiple sclerosis (MS) remains unclear, with some studies demonstrating increased risks of infection with B-cell-depleting (anti-CD20) therapies and severity, while others fail to observe an association. Most existing studies are limited by a reliance on 'numerator' data (i.e., COVID-19 cases) only. OBJECTIVE: To assess the risks of COVID-19 by DMT, this study aimed to assess both 'numerator' (patients with SARS-CoV-2 infection) and 'denominator' data (all patients treated with DMTs of interest) to determine if any DMTs impart an increased risk of SARS-CoV-2 infection or disease severity. METHODS: We systematically reviewed charts and queried patients during clinic encounters in the NYU MS Comprehensive Care Center (MSCCC) for evidence of COVID-19 in all patients who were on the most commonly used DMTs in our clinic (sphingosine-1-phosphate receptor (S1P) modulators (fingolimod/siponimod), rituximab, ocrelizumab, fumarates (dimethyl fumarate/diroximel fumarate), and natalizumab). COVID-19 status was determined by clinical symptoms (CDC case definition) and laboratory testing where available (SARS-CoV-2 PCR, SARS-CoV-2 IgG). Multivariable analyses were conducted to determine predictors of infection and severe disease (hospitalization or death) using SARS-CoV-2 infected individuals per DMT group and all individuals on a given DMT as denominator. RESULTS: We identified 1,439 MS patients on DMTs of interest, of which 230 had lab-confirmed (n = 173; 75.2%) or suspected (n = 57; 24.8%) COVID-19. Infection was most frequent in those on rituximab (35/138; 25.4%), followed by fumarates (39/217; 18.0%), S1P modulators (43/250; 17.2%), natalizumab (36/245; 14.7%), and ocrelizumab (77/589; 13.1%). There were 14 hospitalizations and 2 deaths. No DMT was found to be significantly associated with increased risk of SARS-CoV-2 infection. Rituximab was a predictor of severe SARS-CoV-2 infection among patients with SARS-CoV-2 infection (OR 6.7; 95% CI 1.1-41.7) but did not reach statistical significance when the entire patient population on DMT was used (OR 2.8; 95% CI 0.6-12.2). No other DMT was associated with an increased risk of severe COVID-19. CONCLUSIONS: Analysis of COVID-19 risk among all patients on the commonly used DMTs did not demonstrate increased risk of infection with any DMT. Rituximab was associated with increased risk for severe disease.


Subject(s)
COVID-19 , Multiple Sclerosis , Dimethyl Fumarate/therapeutic use , Humans , Multiple Sclerosis/complications , Multiple Sclerosis/drug therapy , Multiple Sclerosis/epidemiology , Natalizumab/therapeutic use , Rituximab/therapeutic use , SARS-CoV-2
5.
Neurol Neuroimmunol Neuroinflamm ; 9(2)2022 03.
Article in English | MEDLINE | ID: covidwho-1643219

ABSTRACT

BACKGROUND AND OBJECTIVES: Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR). METHODS: A case-control (1:2) study was set up. Cases included PwMS with a confirmed diagnosis of COVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score-matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administered DMT, previous DMT sequences, or the place where the last treatment was administered. RESULTS: A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p < 0.02) with a higher risk of contracting COVID-19. Patients receiving natalizumab as last DMT (OR [95% CI]: 2.38 [1.66-3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16-2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34-2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home. DISCUSSION: This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective.


Subject(s)
COVID-19/epidemiology , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/epidemiology , Adult , Age Factors , Case-Control Studies , Dimethyl Fumarate/therapeutic use , Female , Fingolimod Hydrochloride/therapeutic use , Glatiramer Acetate/therapeutic use , Humans , Interferon-beta/therapeutic use , Italy/epidemiology , Male , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Chronic Progressive/drug therapy , Multiple Sclerosis, Chronic Progressive/epidemiology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Natalizumab/therapeutic use , Odds Ratio , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Time Factors
6.
Neurology ; 97(19): e1870-e1885, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1523377

ABSTRACT

BACKGROUND AND OBJECTIVES: People with multiple sclerosis (MS) are a vulnerable group for severe coronavirus disease 2019 (COVID-19), particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. METHODS: Data from 12 data sources in 28 countries were aggregated (sources could include patients from 1-12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs) covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit (ICU) admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale (EDSS) score. RESULTS: Six hundred fifty-seven (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01-2.41; aOR 2.43, 95% CI 1.48-4.02) and ICU admission (aOR 2.30, 95% CI 0.98-5.39; aOR 3.93, 95% CI 1.56-9.89), although only rituximab was associated with higher risk of artificial ventilation (aOR 4.00, 95% CI 1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization (aOR 1.75, 95% CI 1.29-2.38; aOR 2.76, 95% CI 1.87-4.07) and ICU admission (aOR 2.55, 95% CI 1.49-4.36; aOR 4.32, 95% CI 2.27-8.23), but only rituximab was associated with artificial ventilation (aOR 6.15, 95% CI 3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization (aOR 1.86, 95% CI 1.13-3.07; aOR 2.88, 95% CI 1.68-4.92) and ICU admission (aOR 2.13, 95% CI 0.85-5.35; aOR 3.23, 95% CI 1.17-8.91), but only rituximab was associated with ventilation (aOR 5.52, 95% CI 1.71-17.84). Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity. DISCUSSION: Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19.


Subject(s)
COVID-19/complications , Hospitalization/statistics & numerical data , Multiple Sclerosis/complications , Multiple Sclerosis/drug therapy , Adolescent , Adult , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/pathology , COVID-19/physiopathology , Cross-Sectional Studies , Dimethyl Fumarate/adverse effects , Dimethyl Fumarate/therapeutic use , Female , Humans , Male , Middle Aged , Natalizumab/adverse effects , Natalizumab/therapeutic use , Respiration, Artificial/statistics & numerical data , Rituximab/adverse effects , Rituximab/therapeutic use , SARS-CoV-2 , Young Adult
7.
CNS Drugs ; 35(3): 317-330, 2021 03.
Article in English | MEDLINE | ID: covidwho-1141535

ABSTRACT

BACKGROUND: Disease-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). OBJECTIVE: The 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. METHODS: The 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. RESULTS: 30,478 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. CONCLUSIONS: Comorbidities, 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.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Adolescent , Adult , African Americans/statistics & numerical data , Aged , Aged, 80 and over , Alemtuzumab/therapeutic use , Azathioprine/therapeutic use , COVID-19/mortality , Cladribine/therapeutic use , Comorbidity , Crotonates/therapeutic use , Cyclophosphamide/therapeutic use , Cyclosporine/therapeutic use , Databases, Factual , Dimethyl Fumarate/therapeutic use , Female , Fingolimod Hydrochloride/therapeutic use , Humans , Hydroxybutyrates , Immunologic Factors/therapeutic use , Incidence , Interferon-beta/therapeutic use , Logistic Models , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , Male , Methotrexate/therapeutic use , Middle Aged , Mitoxantrone/therapeutic use , Multiple Sclerosis/epidemiology , Mycophenolic Acid/therapeutic use , Natalizumab/therapeutic use , Nitriles , Obesity/epidemiology , Risk Factors , Rituximab/therapeutic use , SARS-CoV-2 , Toluidines/therapeutic use , United States/epidemiology , Young Adult
9.
Ann Neurol ; 89(4): 780-789, 2021 04.
Article in English | MEDLINE | ID: covidwho-1070695

ABSTRACT

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


Subject(s)
COVID-19/physiopathology , Hospitalization/statistics & numerical data , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , COVID-19/mortality , Dimethyl Fumarate/therapeutic use , Female , Fingolimod Hydrochloride/therapeutic use , Humans , Immunologic Factors/therapeutic use , Intensive Care Units/statistics & numerical data , Interferons/therapeutic use , Male , Middle Aged , Mortality , Multiple Sclerosis/complications , Natalizumab/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Young Adult
11.
Biochemistry (Mosc) ; 85(7): 833-837, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-772260

ABSTRACT

Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages. Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the inflammatory cytokines in macrophages. Critically ill patients with COVID-19 infection often present signs of high oxidative stress and systemic inflammation - the leading causes of mortality. This article suggests rationale for the use of Nrf2 inducers to prevent development of an excessive inflammatory response in COVID-19 patients.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/metabolism , Cytokines/antagonists & inhibitors , Cytokines/metabolism , Molecular Targeted Therapy/methods , NF-E2-Related Factor 2/metabolism , Pneumonia, Viral/drug therapy , Pneumonia, Viral/metabolism , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , COVID-19 , Catechin/analogs & derivatives , Catechin/pharmacology , Catechin/therapeutic use , Coronavirus Infections/virology , Dimethyl Fumarate/pharmacology , Dimethyl Fumarate/therapeutic use , Female , Humans , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Inflammation/metabolism , Isothiocyanates/pharmacology , Isothiocyanates/therapeutic use , Male , Mice , Oxidative Stress/drug effects , Pandemics , Pneumonia, Viral/virology , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/virology , Resveratrol/pharmacology , Resveratrol/therapeutic use , SARS-CoV-2 , Signal Transduction/drug effects , Sulfoxides , Thiosulfates/pharmacology , Thiosulfates/therapeutic use
16.
Mult Scler Relat Disord ; 43: 102195, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-245403

ABSTRACT

OBJECTIVE: To determine whether the course of COVID-19 is more severe in patients with MS and if MS disease-modifying treatments (DMTs) affect the risk of contracting the disease. METHODS: In a cross-sectional survey, data were collected by sending a questionnaire to 2000 patients with a demyelinating disease through an online portal system. Collected data included the current MS DMT and patient-reported disability level, history of recent sick contact, recent fever, respiratory symptoms, diagnosis with COVID-19, and the disposition after the diagnosis. We defined a COVID-19-suspect group as patients having fever and cough or fever and shortness of breath, or a presumptive diagnosis based on suggestive chest computed tomography. We calculated the proportion of COVID-19-suspect patients and compared their demographics, clinical characteristics, and DMT categories with the rest of survey-responders, using univariable and multivariable models. RESULTS: Out of 712 patients, 34 (4.8%) fulfilled our criteria for being in the COVID-19-suspect group. Only two patients required hospitalization. No patient required intensive care. In a multivariable model, disease duration (p-value=0.017), DMT category (p-value=0.030), and history of sick contact (p-values<0.001) were associated with the risk of being in the COVID-19-suspect group. Being on B-cell depleting antibodies (as compared to non-cell depleting, non-cell trafficking inhibitor DMTs) was associated with a 2.6-fold increase in the risk of being in the COVID-19-suspect group. (RR: 3.55, 95%CI: 1.45, 8.68, p-value=0.005). CONCLUSIONS: The course of infection in patients with MS suspected of having COVID-19 was mild to moderate, and all patients had a full recovery. B-cell depleting antibodies may increase the susceptibility to contracting COVID-19.


Subject(s)
Coronavirus Infections/immunology , Immunocompromised Host/immunology , Immunologic Factors/therapeutic use , Multiple Sclerosis/drug therapy , Pneumonia, Viral/immunology , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , B-Lymphocytes/immunology , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Cough , Cross-Sectional Studies , Crotonates/therapeutic use , Dimethyl Fumarate/therapeutic use , Disease Susceptibility , Dyspnea , Epidemics , Female , Fever , Fingolimod Hydrochloride/therapeutic use , Glatiramer Acetate/therapeutic use , Hospitalization/statistics & numerical data , Humans , Hydroxybutyrates , Intensive Care Units/statistics & numerical data , Interferons/therapeutic use , Iran/epidemiology , Lung/diagnostic imaging , Lymphocyte Depletion , Male , Multiple Sclerosis/complications , Multiple Sclerosis, Chronic Progressive/drug therapy , Multiple Sclerosis, Chronic Progressive/epidemiology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Natalizumab/therapeutic use , Nitriles , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Rituximab/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Toluidines/therapeutic use , Tomography, X-Ray Computed
17.
Mult Scler Relat Disord ; 43: 102174, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-232477

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.


Subject(s)
Betacoronavirus/immunology , CD8-Positive T-Lymphocytes/immunology , Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Immunosuppressive Agents/therapeutic use , Lymphopenia/immunology , Multiple Sclerosis/therapy , Pneumonia, Viral/immunology , Alemtuzumab/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Viral/immunology , COVID-19 , Cladribine/therapeutic use , Crotonates/therapeutic use , Deprescriptions , Dimethyl Fumarate/therapeutic use , Fingolimod Hydrochloride/therapeutic use , Glatiramer Acetate/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Humans , Hydroxybutyrates , Immune Evasion/immunology , Immunity, Innate/immunology , Immunologic Factors/therapeutic use , Interferon-beta/therapeutic use , Macrophages/immunology , Monocytes/immunology , Natalizumab/therapeutic use , Nitriles , Pandemics , Respiratory Distress Syndrome/immunology , SARS-CoV-2 , Toluidines/therapeutic use
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