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1.
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
2.
Mult Scler Relat Disord ; 57: 103435, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1616671

ABSTRACT

OBJECTIVE: The aim of this study is to determine a development of humoral response after COVID-19 vaccination in persons with secondary progressive multiple sclerosis (pwSPMS) on siponimod, compared to healthy controls (HC). METHODS: In 13 pwSPMS taking siponimod and 11 HC, testing for SARS-CoV2 antibodies was performed after vaccination against COVID-19. RESULTS: pwSPMS taking siponimod had a significantly lower titer of SARS-CoV2 antibodies compared to healthy controls (19.4 (0-250) vs. 250 (250), p>0.001). Two (15.4%) pwSPMS on siponimod had unmeasurable titers of SARS-CoV2-2 antibodies, while all HC had positive titers. CONCLUSION: Although the results of this study are limited by a small sample size, results have consistently shown low titers of SARS-CoV-2 IgG after COVID-19 vaccinations in pwSPMS on siponimod.


Subject(s)
COVID-19 , Multiple Sclerosis, Chronic Progressive , Multiple Sclerosis , Antibodies, Viral , Azetidines , Benzyl Compounds , COVID-19 Vaccines , Humans , Immunity, Humoral , Multiple Sclerosis, Chronic Progressive/drug therapy , RNA, Viral , SARS-CoV-2 , Vaccination
3.
Neurol Neuroimmunol Neuroinflamm ; 8(5)2021 07.
Article in English | MEDLINE | ID: covidwho-1282284

ABSTRACT

OBJECTIVE: To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. METHODS: Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. RESULTS: Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. CONCLUSIONS: This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal disease.


Subject(s)
COVID-19/physiopathology , Immunocompromised Host , Immunosuppressive Agents/administration & dosage , Multiple Sclerosis, Chronic Progressive/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Registries , Severity of Illness Index , Adult , Age Factors , COVID-19/epidemiology , Comorbidity , Female , Humans , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Multiple Sclerosis, Chronic Progressive/epidemiology , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Neurology , Retrospective Studies , Risk Factors , Sex Factors , Societies, Medical , Spain
4.
Ann Clin Transl Neurol ; 8(2): 385-394, 2021 02.
Article in English | MEDLINE | ID: covidwho-995827

ABSTRACT

OBJECTIVE: Pivotal trial have shown that patients with multiple sclerosis (MS) receiving ocrelizumab had better outcomes. However, data on ocrelizumab in clinical practice are limited. The aim of this study was to evaluate the preliminary safety profile and effectiveness of ocrelizumab treatment for multiple sclerosis (MS) in a real-world clinical setting. METHODS: We conducted a retrospective study including consecutive patients from nine public hospitals in south-eastern Spain who received ocrelizumab after it was approved. RESULTS: A total of 228 MS patients were included (144 with relapsing-remitting MS [RRMS], 25 secondary progressive MS [SPMS], and 59 primary progressive MS [PPMS]). Median follow-up period was 12 months (range, 1-32). No evidence of disease activity (NEDA) status at year 1 was achieved in 91.2% of the relapsing MS (RMS) population, while disability progression was detected in 37.5% of the PPMS patients (median follow-up period, 19 months). The most common adverse events reported were infusion-related reactions and infections, with the most common infections being urinary tract infections followed by upper respiratory infections and COVID-19. INTERPRETATION: The preliminary results in our real-world setting show that ocrelizumab presented excellent results in suppressing disease activity with a favorable and consistent safety profile.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Immunologic Factors/therapeutic use , Multiple Sclerosis, Chronic Progressive/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Adult , Brain/diagnostic imaging , Disease Progression , Female , Humans , Injection Site Reaction , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis, Chronic Progressive/diagnostic imaging , Multiple Sclerosis, Chronic Progressive/physiopathology , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Retrospective Studies , Spain , Spinal Cord/diagnostic imaging , Treatment Outcome
5.
Mult Scler Relat Disord ; 48: 102704, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-988914

ABSTRACT

OBJECTIVE: To evaluate clinical and laboratory effects of delaying ocrelizumab infusions during the COVID-19 pandemics in people with multiple sclerosis (pwMS). METHODS: We have retrospectively searched our electronic database and identified 33 pwMS who had a delay in treatment due to COVID-19 pandemics. The following data were extracted: age, sex, multiple sclerosis (MS) phenotype: relapsing-remitting (RRMS) or primary progressive multiple sclerosis (PPMS), disease duration, Expanded Disability Status scale (EDSS), previous disease modifying therapy (DMT), number of ocrelizumab cycles prior to the lockdown, dates of first ocrelizumab infusion, last ocrelizumab infusion prior to the lockdown and delayed ocrelizumab infusion after the lockdown. Flow cytometry results, relapses and EDSS progression prior to the delayed ocrelizumab infusion after the lockdown were extracted. RESULTS: The mean time between two ocrelizumab infusion during the lockdown was 7.72±0.64 (range 6.07 to 8.92) months. The mean time between last ocrelizumab infusion and the lymphocyte sampling prior to post COVID infusion was 6.59±0.95 (range 5.18 to 8.49) months. In this period, none of the studied patients had a relapse. In a multivariable linear regression analysis, time from last ocrelizumab infusion to lymphocyte sampling prior to the next infusion was the only significant predictor for CD19+ B cells count, when corrected for the number of previous ocrelizumab cycles and MS phenotype (RRMS or PPMS) (B=7.981, 95% C.I. 3.277-12.686, p=0.002). CONCLUSIONS: We have not shown clinical consequences of delaying ocrelizumab due to COVID-19 pandemics. However, the delay in dosing of ocrelizumab was an independent predictor of repopulation of B cells.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19 , Immunologic Factors/administration & dosage , Multiple Sclerosis, Chronic Progressive/drug therapy , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Adult , Female , Humans , Male , Middle Aged , Multiple Sclerosis, Chronic Progressive/blood , Multiple Sclerosis, Chronic Progressive/immunology , Multiple Sclerosis, Relapsing-Remitting/blood , Multiple Sclerosis, Relapsing-Remitting/immunology , Retrospective Studies , Time Factors , Time-to-Treatment
6.
Mult Scler ; 26(10): 1261-1264, 2020 09.
Article in English | MEDLINE | ID: covidwho-696957

ABSTRACT

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


Subject(s)
B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , Coronavirus Infections/immunology , Immunity, Cellular/immunology , Killer Cells, Natural/immunology , Multiple Sclerosis, Chronic Progressive/drug therapy , Pneumonia, Viral/immunology , Rituximab/therapeutic use , Betacoronavirus , CD4-CD8 Ratio , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Disease Progression , Female , Humans , Lymphocyte Count , Middle Aged , Multiple Sclerosis, Chronic Progressive/complications , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , SARS-CoV-2
9.
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
11.
Mult Scler Relat Disord ; 42: 102120, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-101811

ABSTRACT

BACKGROUND: Coronavirus disease 19 (COVID-19) is a novel disease entity that is spreading throughout the world. It has been speculated that patients with comorbidities and elderly patients could be at high risk for respiratory insufficiency and death. Immunosuppression could expose infected patients to even higher risks of disease complications due to dampened immune response. However, it has been speculated that overactive immune response could drive clinical deterioration and, based on this hypothesis, several immunosuppressants are currently being tested as potential treatment for COVID-19. METHODS: In this paper we report on a patient that has been treated with ocrelizumab (a B-cell depleting monoclonal antibody) for primary progressive multiple sclerosis who developed COVID-19. RESULTS: Despite complete B cell depletion, patient symptoms abated few days after hospitalization, and he was discharged to home-quarantine. Phone interview follow-up confirmed that, after 14 days, no new symptoms occurred. DISCUSSION: This report supports the putative role of immunosuppressive therapy in COVID-19 affected patients.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Coronavirus Infections/physiopathology , Immunologic Factors/therapeutic use , Multiple Sclerosis, Chronic Progressive/drug therapy , Pneumonia, Viral/physiopathology , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Humans , Male , Middle Aged , Multiple Sclerosis, Chronic Progressive/complications , Pandemics , Pneumonia, Viral/complications , Protective Factors , SARS-CoV-2 , Severity of Illness Index
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