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      Outcomes and Risk Factors Associated With SARS-CoV-2 Infection in a North American Registry of Patients With Multiple Sclerosis

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          Abstract

          This cross-sectional study examines outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with multiple sclerosis.

          Key Points

          Question

          How do patients with multiple sclerosis (MS) who have COVID-19 fare and are there patient and disease characteristics associated with worse outcome?

          Findings

          In this registry-based cross-sectional study of 1626 North American patients with MS and COVID-19 infection, ambulatory disability, both nonambulatory and requiring assistance to walk, was independently associated with increased odds of poor clinical severity levels after adjusting for other risk factors. Other factors including older age, male sex, Black race, cardiovascular comorbidities, and corticosteroid use in the past 2 months were associated with increased odds of increasing clinical severity compared with those not requiring hospitalization or worse.

          Meaning

          Identification of risk factors can improve the treatment of patients with MS and COVID-19 by alerting clinicians of patients requiring more intense treatment or monitoring.

          Abstract

          Importance

          Emergence of SARS-CoV-2 causing COVID-19 prompted the need to gather information on clinical outcomes and risk factors associated with morbidity and mortality in patients with multiple sclerosis (MS) and concomitant SARS-CoV-2 infections.

          Objective

          To examine outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with MS.

          Design, Setting, and Participants

          This analysis used deidentified, cross-sectional data on patients with MS and SARS-CoV-2 infection reported by health care professionals in North American academic and community practices between April 1, 2020, and December 12, 2020, in the COVID-19 Infections in MS Registry. Health care professionals were asked to report patients after a minimum of 7 days from initial symptom onset and after sufficient time had passed to observe the COVID-19 disease course through resolution of acute illness or death. Data collection began April 1, 2020, and is ongoing.

          Exposures

          Laboratory-positive SARS-CoV-2 infection or highly suspected COVID-19.

          Main Outcomes and Measures

          Clinical outcome with 4 levels of increasing severity: not hospitalized, hospitalization only, admission to the intensive care unit and/or required ventilator support, and death.

          Results

          Of 1626 patients, most had laboratory-positive SARS-CoV-2 infection (1345 [82.7%]), were female (1202 [74.0%]), and had relapsing-remitting MS (1255 [80.4%]). A total of 996 patients (61.5%) were non-Hispanic White, 337 (20.8%) were Black, and 190 (11.7%) were Hispanic/Latinx. The mean (SD) age was 47.7 (13.2) years, and 797 (49.5%) had 1 or more comorbidity. The overall mortality rate was 3.3% (95% CI, 2.5%-4.3%). Ambulatory disability and older age were each independently associated with increased odds of all clinical severity levels compared with those not hospitalized after adjusting for other risk factors (nonambulatory: hospitalization only, odds ratio [OR], 2.8 [95% CI, 1.6-4.8]; intensive care unit/required ventilator support, OR, 3.5 [95% CI, 1.6-7.8]; death, OR, 25.4 [95% CI, 9.3-69.1]; age [every 10 years]: hospitalization only, OR, 1.3 [95% CI, 1.1-1.6]; intensive care unit/required ventilator support, OR, 1.3 [95% CI, 0.99-1.7]; death, OR, 1.8 [95% CI, 1.2-2.6]).

          Conclusions and Relevance

          In this registry-based cross-sectional study, increased disability was independently associated with worse clinical severity including death from COVID-19. Other risk factors for worse outcomes included older age, Black race, cardiovascular comorbidities, and recent treatment with corticosteroids. Knowledge of these risk factors may improve the treatment of patients with MS and COVID-19 by helping clinicians identify patients requiring more intense monitoring or COVID-19 treatment.

          Related collections

          Most cited references27

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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            • Article: not found

            Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support.

            Research electronic data capture (REDCap) is a novel workflow methodology and software solution designed for rapid development and deployment of electronic data capture tools to support clinical and translational research. We present: (1) a brief description of the REDCap metadata-driven software toolset; (2) detail concerning the capture and use of study-related metadata from scientific research teams; (3) measures of impact for REDCap; (4) details concerning a consortium network of domestic and international institutions collaborating on the project; and (5) strengths and limitations of the REDCap system. REDCap is currently supporting 286 translational research projects in a growing collaborative network including 27 active partner institutions.
              • Record: found
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              Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

              Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.

                Author and article information

                Journal
                JAMA Neurol
                JAMA Neurol
                JAMA Neurol
                JAMA Neurology
                American Medical Association
                2168-6149
                2168-6157
                19 March 2021
                June 2021
                3 May 2021
                19 March 2021
                : 78
                : 6
                : 1-10
                Affiliations
                [1 ]Washington University School of Medicine in St Louis, St Louis, Missouri
                [2 ]Cleveland Clinic, Cleveland, Ohio
                [3 ]Johns Hopkins University School of Medicine, Baltimore, Maryland
                [4 ]Consortium of MS Centers, Hackensack, New Jersey
                [5 ]The University of British Columbia, Vancouver, British Columbia, Canada
                [6 ]MS Society of Canada, Toronto, Ontario, Canada
                [7 ]National Multiple Sclerosis Society, Chicago, Illinois
                [8 ]University of Miami School of Medicine, Miami, Florida
                [9 ]The University of Alabama at Birmingham, Birmingham
                Author notes
                Article Information
                Corresponding Author: Amber Salter, PhD, Division of Biostatistics, Washington University in St Louis, 660 Euclid Ave, Campus Box 8067, St Louis, MO 63110-1093 ( amber@ 123456wustl.edu ).
                Accepted for Publication: February 19, 2021.
                Published Online: March 19, 2021. doi:10.1001/jamaneurol.2021.0688
                Correction: This article was corrected on May 3, 2021, to fix an error in the Discussion.
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Salter A et al. JAMA Neurology.
                Author Contributions: Dr Salter had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Salter, Fox, Newsome, Li, Costello, Bebo, Rammohan, Cutter, Cross.
                Acquisition, analysis, or interpretation of data: Salter, Fox, Newsome, Halper, Li, Kanellis, Bebo, Rammohan, Cutter, Cross.
                Drafting of the manuscript: Salter, Halper, Cross.
                Critical revision of the manuscript for important intellectual content: Fox, Newsome, Li, Kanellis, Costello, Bebo, Rammohan, Cutter, Cross.
                Statistical analysis: Salter, Cutter.
                Obtained funding: Bebo, Cutter.
                Administrative, technical, or material support: Salter, Li, Kanellis, Bebo, Rammohan, Cutter, Cross.
                Supervision: Newsome, Bebo.
                Conflict of Interest Disclosures: Dr Salter reports grants from National Multiple Sclerosis Society and is a statistical editor for Circulation: Cardiovascular Imaging during the conduct of the study. Dr Fox reports personal fees from AB Science, Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic Therapeutics, Novartis, Sanofi, Teva Pharmaceutical, and TG Therapeutics and clinical trial contract and research grant funding from Biogen and Novartis during the conduct of the study. Dr Newsome reports personal fees from Biogen, Novartis, Genentech, Bristol Myers Squibb, EMD Serono, Greenwich Biosciences, BioIncept, Autobahn, Celgene, and MedDay and other support from Biogen, Novartis, Genentech, National Multiple Sclerosis Society, US Department of Defense, and Patient-Centered Outcomes Research Institute paid to their institution outside the submitted work. Dr Li reports personal fees from Biogen and personal fees from Sanofi Genzyme; grants from Sanofi Genzyme, Roche, Novartis, and MS Society of Canada; is emeritus director of the University of British Columbia Multiple Sclerosis/Magnetic Resonance Imaging Research Group, which has been contracted to perform central analysis of magnetic resonance imaging scans for therapeutic trials with Roche and SanofiGenzyme and has received grant support for investigator-initiated studies from Sanofi Genzyme, Novartis, and Roche; and has served on the Progressive Multifocal Leukoencephalopathy–Multiple Sclerosis Steering Committee for Biogen and given lectures, supported by nonrestricted education grants from Academy of Healthcare Learning, Biogen, Consortium of Multiple Sclerosis Centers, and Sanofi Genzyme outside the submitted work. Dr Rammohan reports grants from Biogen, Novartis, Genzyme, Roche Genentech, Alexion, EMD Serono, MedDay Pharma, TG Therapeutics, and US Department of Defense and personal fees from Biogen, Novartis, Genzyme, Roche Genentech, Alexion, and EMD Serono outside the submitted work. Dr Cutter reports personal fees for serving on the data and safety monitoring boards of AstraZeneca, AveXis Pharmaceuticals, BioLineRx, Brainstorm Cell Therapeutics, Bristol Myers Squibb/Celgene, CSL Behring, Galmed Pharmaceuticals, Green Valley Pharma, Horizon Therapeutics, Hisun Pharmaceuticals, Mapi Pharma, Merck, Merck/Pfizer, Opko Biologics, OncoImmune, Neurim Pharmaceuticals, Novartis, Ophazyme, Sanofi-Aventis, Reata Pharmaceuticals, Teva Pharmaceuticals, Viela Bio, Vivus, National Heart, Lung, and Blood Institute (protocol review committee), Eunice Kennedy Shriver National Institute of Child Health and Human Development (obstetric pharmacology research units oversight committee); personal fees from consulting or serving on advisory boards of BioDelivery Sciences International, Biogen, Click Therapeutics, Genzyme, Genentech, GW Pharmaceuticals, Immunic, Klein Buendel, Medimmune/Viela Bio, MedDay, Merck/Serono, Neurogenesis, Novartis, Osmotica Pharmaceuticals, Perception Neuroscience, Recursion/CereXis Pharmaceuticals, Regeneron, Reckover Pharmaceuticals, Roche, and TG Therapeutics; and is President of Pythagoras Inc, a private consulting company. Dr Cross reports personal fees from Biogen, Celgene (Bristol Myers Squibb), EMD Serono, Genentech, Greenwich Biosciences, Janssen, Novartis, and TG Therapeutics outside the submitted work; grants from EMD Serono and Genentech outside the submitted work; and is secretary of the Consortium of Multiple Sclerosis Centers Board of Governors (an elected position), which is a supporter of the COVID-19 Infections in MS Registry, along with National Multiple Sclerosis Society (US) and MS Society of Canada. No other disclosures were reported.
                Funding/Support: Support for the COVID-19 Infections in MS Registry is provided by the National Multiple Sclerosis Society, the Consortium of Multiple Sclerosis Centers, and the MS Society of Canada. REDCap at Washington University in St Louis is supported by Clinical and Translational Science Award (CTSA) (grant UL1 TR000448) and Siteman Comprehensive Cancer Center and National Cancer Institute Cancer Center Support Grant (grant P30 CA091842).
                Role of the Funder/Sponsor: The National Multiple Sclerosis Society had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Additional Contributions: The COVID-19 Infections in MS Registry had robust participation from health care professionals across North America and we would like to thank all those who contributed information to this effort.
                Article
                noi210015
                10.1001/jamaneurol.2021.0688
                7980147
                33739362
                383d026d-9b6b-4d1f-8fa7-e7d9eadc3f59
                Copyright 2021 Salter A et al. JAMA Neurology.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 26 October 2020
                : 19 February 2021
                Funding
                Funded by: National Multiple Sclerosis Society
                Funded by: Consortium of Multiple Sclerosis Centers
                Funded by: MS Society of Canada
                Funded by: Clinical and Translational Science Award (CTSA)
                Funded by: Siteman Comprehensive Cancer Center
                Funded by: National Cancer Institute Cancer Center Support Grant
                Categories
                Research
                Research
                Original Investigation
                Online First
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