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Observational Study
. 2020 Sep 1;77(9):1079-1088.
doi: 10.1001/jamaneurol.2020.2581.

Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis

Céline Louapre  1 , Nicolas Collongues  2 , Bruno Stankoff  1   3 , Claire Giannesini  3 , Caroline Papeix  1 , Caroline Bensa  4 , Romain Deschamps  4 , Alain Créange  5 , Abir Wahab  5 , Jean Pelletier  6 , Olivier Heinzlef  7 , Pierre Labauge  8 , Laurent Guilloton  9 , Guido Ahle  10 , Mathilde Goudot  11 , Kevin Bigaut  2 , David-Axel Laplaud  12 , Sandra Vukusic  13 , Catherine Lubetzki  1 , Jérôme De Sèze  2 ; Covisep investigators; Fayçal Derouiche, Ayman Tourbah, Guillaume Mathey, Marie Théaudin, François Sellal, Marie-Hélène Dugay, Helene Zéphir, Patrick Vermersch, Françoise Durand-Dubief, Romain Françoise, Géraldine Androdias-Condemine, Julie Pique, Pékès Codjia, Caroline Tilikete, Véronique Marcaud, Christine Lebrun-Frenay, Mikael Cohen, Aurelian Ungureanu, Elisabeth Maillart, Ysoline Beigneux, Thomas Roux, Jean-Christophe Corvol, Amandine Bordet, Yanica Mathieu, Frédérique Le Breton, Dalia Dimitri Boulos, Olivier Gout, Antoine Guéguen, Antoine Moulignier, Marine Boudot, Audrey Chardain, Sarah Coulette, Eric Manchon, Samar S. Ayache, Thibault Moreau, Pierre-Yves Garcia, Deiva Kumaran, Giovanni Castelnovo, Eric Thouvenot, Frederic Taithe, Julien Poupart, Arnaud Kwiatkowski, Gilles Defer, Nathalie Derache, Pierre Branger, Damien Biotti, Jonathan Ciron, Christine Clerc, Mathieu Vaillant, Laurent Magy, Alexis Montcuquet, Philippe Kerschen, Marc Coustans, Anne-Marie Guennoc, Bruno Brochet, Jean-Christophe Ouallet, Aurélie Ruet, Cécile Dulau, Sandrine Wiertlewski, Eric Berger, Dan Buch, Bertrand Bourre, Maud Pallix-Guiot, Aude Maurousset, Bertrand Audoin, Audrey Rico, Adil Maarouf, Gilles Edan, Jérémie Papassin, Dorothée Videt
Affiliations
Observational Study

Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis

Céline Louapre et al. JAMA Neurol. .

Abstract

Importance: Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities.

Objective: To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity.

Design, setting, and participants: The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020.

Exposures: COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms.

Main outcomes and measures: The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes.

Results: A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01).

Conclusions and relevance: In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva and Merck Serono, outside the submitted work. Dr Collongues serves on scientific advisory boards for and has received honoraria from Biogen Idec, Merck Serono, Sanofi-Genzyme, Bayer Schering Pharma and Alexion Pharmaceutical, and personal fees and nonfinancial support from Roche, Biogen, Novartis, Sanofi, and MedDay outside the submitted work outside the submitted work. Dr Stankoff has received fees for advisory boards and lectures from Genzyme, Novartis, Teva, and Biogen and research support from Roche, Sanofi-Genzyme, and Merck-Serono outside the submitted work. Dr Papeix has received consulting and lecturing fees and travel grants from Biogen, Genzyme, Novartis, Merck, Roche, Sanofi, and Teva Pharma outside the submitted work. Dr Bensa has received consulting fees for advisory boards from Biogen, Novartis, Roche, and Sanofi Genzyme outside the submitted work. Dr Deschamps has received travel grants from Biogen outside the submitted work. Dr Créange has received departmental research grants from Biogen, GeNeuro, MedDay, Novartis, Octapharma, and Roche; completed expert testimony with Biogen, Novartis, GeNeuro, and Roche; and received grants and personal fees from MedDay outside the submitted work. Dr Wahab has received expert testimony fees from Sanofi-Genzyme and Roche and travel grants from Biogen and Roche outside the submitted work. Dr Pelletier has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, MedDay, and Merck Serono outside the submitted work. Dr Heinzlef has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, Merck Serono, and MedDay outside the submitted work. Dr Guilloton has received consulting or travel fees from Biogen, Merck Serono, Novartis, Sanofi, and Teva outside the submitted work. Dr Ahle has received consulting or travel fees from AbbVie, Biogen, Novartis, Roche, and Sanofi outside the submitted work and reported grants from Roche, Novartis, Biogen, and Sanofi during the conduct of the study. Dr Bigaut has received travel grants from Biogen Idec and Sanofi-Genzyme outside the submitted work. Dr Laplaud has received grants from the ARSEP Foundation and MedDay; personal fees from Biogen, Sanofi-Genzyme, Merck, Celgene, Roche, MedDay, and Teva; grants and personal fees from Novartis; and consulting and lecturing fees, travel grants, and unconditional research support from Biogen, Genzyme, Novartis, Merck Serono, Roche, Sanofi-Aventis, and Teva Pharma outside the submitted work. Dr Vukusic has received grants, personal fees and nonfinancial support from Biogen, Merck, Novartis, Sanofi-Genzyme, Roche, Teva, Celgene, and MedDay and grants from Novartis, Roche, Sanofi, and Teva outside the submitted work. Dr Lubetzki reports grants and personal fees from Biogen and personal fees from Merck-Serono, Roche, Rewind, and Ipsen outside the submitted work. Dr De Sèze has received consulting fees from Biogen, Roche, Novartis, Teva, Cellgen, Jansen, and Sanofi-Genzyme and contracted research from Novartis and Sanofi-Genzyme outside the submitted work.

Figures

Figure 1.
Figure 1.. Clinical Condition Rating at Nadir and Disease-Modifying Therapies in Patients With Multiple Sclerosis
A, Patients were grouped according to coronavirus disease 2019 (COVID-19) severity score (from 1 [not hospitalized with no limitations on activities] to 7 [death]). B, Patients were grouped according to disease-modifying therapy. Systemic immunosuppression risk was adapted from Brownlee et al. Other treatments used by patients with multiple sclerosis included mycophenolate mofetil (n = 3), cyclophosphamide (n = 1), and methotrexate (n = 1).
Figure 2.
Figure 2.. Characteristics of Patients Not Hospitalized for Coronavirus Disease 2019 (COVID-19) and Patients Who Were Hospitalized With or Died of COVID-19
A, Age. B, Expanded Disability Severity Scale (EDSS) score. C, Clinical course. The P values were obtained from Mann-Whitney U tests for age and EDSS group differences and χ2 tests for clinical course distribution differences.
Figure 3.
Figure 3.. Risk Factors of Severe Coronavirus Disease 2019 (COVID-19)
Severe COVID-19 was defined as a severity score of 3 or more. A, Univariate analysis. B, Multivariate analysis. Results are expressed as odds ratios (ORs) with 95% CIs. C, Cumulative variability (McFadden R2) of severe COVID-19 accounted for each variable retained in the multiple logistic regression model. Numbers of patients per category: men, 98; with 1 or more comorbidity, 113; with obesity, 24; with cardiac comorbidity, 23; with an Expanded Disability Severity Status (EDSS) score less than 3, 194; with an EDSS of 3 to 5.5, 75; with an EDSS of 6 or more, 69; without disease-modifying therapy, 63; receiving interferon or glatiramer acetate, 53; receiving teriflunomide, dimethylfumarate, natalizumab, or other drugs, 130; and receiving fingolimod, ocrelizumab, rituximab, cladribine, or alemtuzumab, 101. NA indicates not applicable.
Figure 4.
Figure 4.. Plot Associating Expanded Disability Severity Scale (EDSS) Score, Age, and Coronavirus Disease 2019 (COVID-19) Severity Score
Letters a to p refer to case reports of patients in need of mechanical ventilation or extracorporeal membrane oxygenation, or dead of COVID-19, as detailed in eTable 1 in the Supplement.
See this image and copyright information in PMC

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