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      Disease‐Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

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          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

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          Most cited references33

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          mice: Multivariate Imputation by Chained Equations inR

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            Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

            Summary Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.
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              Is Open Access

              Autoantibodies against type I IFNs in patients with life-threatening COVID-19

              The genetics underlying severe COVID-19 The immune system is complex and involves many genes, including those that encode cytokines known as interferons (IFNs). Individuals that lack specific IFNs can be more susceptible to infectious diseases. Furthermore, the autoantibody system dampens IFN response to prevent damage from pathogen-induced inflammation. Two studies now examine the likelihood that genetics affects the risk of severe coronavirus disease 2019 (COVID-19) through components of this system (see the Perspective by Beck and Aksentijevich). Q. Zhang et al. used a candidate gene approach and identified patients with severe COVID-19 who have mutations in genes involved in the regulation of type I and III IFN immunity. They found enrichment of these genes in patients and conclude that genetics may determine the clinical course of the infection. Bastard et al. identified individuals with high titers of neutralizing autoantibodies against type I IFN-α2 and IFN-ω in about 10% of patients with severe COVID-19 pneumonia. These autoantibodies were not found either in infected people who were asymptomatic or had milder phenotype or in healthy individuals. Together, these studies identify a means by which individuals at highest risk of life-threatening COVID-19 can be identified. Science, this issue p. eabd4570, p. eabd4585; see also p. 404

                Author and article information

                Contributors
                marco.salvetti@uniroma1.it
                Journal
                Ann Neurol
                Ann Neurol
                10.1002/(ISSN)1531-8249
                ANA
                Annals of Neurology
                John Wiley & Sons, Inc. (Hoboken, USA )
                0364-5134
                1531-8249
                09 February 2021
                April 2021
                : 89
                : 4 ( doiID: 10.1002/ana.v89.4 )
                : 780-789
                Affiliations
                [ 1 ] Department of Health Sciences University of Genoa Genoa Italy
                [ 2 ] IRCCS Ospedale Policlinico San Martino Genoa Italy
                [ 3 ] Centro Sclerosi Multipla ASST Spedali Civili di Brescia Montichiari Italy
                [ 4 ] Department of Neurology Multiple Sclerosis Center, IRCCS Ospedale San Raffaele Milan Italy
                [ 5 ] Department of Neurology and Multiple Sclerosis Center ASST Papa Giovanni XXIII Bergamo Italy
                [ 6 ] Multiple Sclerosis Center Ospedale Guglielmo da Saliceto Piacenza Italy
                [ 7 ] Department of Neurology, Regional Referral Multiple Sclerosis Center University Hospital San Luigi Orbassano Torino Italy
                [ 8 ] Department of Basic Medical Sciences, Neurosciences, and Sense Organs University of Bari Bari Italy
                [ 9 ] Research Department Italian Multiple Sclerosis Foundation Genoa Italy
                [ 10 ] Department of Advanced Medical and Surgical Sciences University of Campania Naples Italy
                [ 11 ] Institute of Experimental Neurology, IRCCS Ospedale San Raffaele Milan Italy
                [ 12 ] Department of Life Sciences University of Siena Siena Italy
                [ 13 ] Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia University of Catania Catania Italy
                [ 14 ] Centro Sclerosi Multipla Policlinico Catania, University of Catania Catania Italy
                [ 15 ] Department of Neuroscience, Mental Health, and Sensory Organs Sapienza University of Rome Rome Italy
                [ 16 ] Unit of Neurology, IRCCS Neuromed Pozzilli Italy
                Author notes
                [*] [* ] Address correspondence to Dr Salvetti, Dipartimento di Neuroscienze, Salute Mentale e Organi di Senso, AOU S. Andrea, via di Grottarossa 1035‐1039, 00189‐Rome, Italy. E‐mail: marco.salvetti@ 123456uniroma1.it

                Author information
                https://orcid.org/0000-0001-6892-104X
                https://orcid.org/0000-0002-6989-1054
                https://orcid.org/0000-0002-6923-0846
                Article
                ANA26028
                10.1002/ana.26028
                8013440
                33480077
                f3ff8a23-0490-42a8-8f84-29ddd29f85ab
                © 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 18 January 2021
                : 11 November 2020
                : 18 January 2021
                Page count
                Figures: 1, Tables: 4, Pages: 10, Words: 7071
                Funding
                Funded by: F. Hoffmann‐La Roche , open-funder-registry 10.13039/100007013;
                Award ID: donating the web‐based platform for data collectio
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                April 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.1 mode:remove_FC converted:01.04.2021

                Neurology
                Neurology

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