Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Diversity, Equity, & Inclusion (DEI)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Diversity, Equity, & Inclusion (DEI)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

User menu

  • My Alerts
  • Log in

Search

  • Advanced search
Neurology Neuroimmunology & Neuroinflammation
Home
A peer-reviewed clinical and translational neurology open access journal
  • My Alerts
  • Log in
Site Logo
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

Share

July 2021; 8 (4) Views & ReviewsOpen Access

COVID-19 Among Patients With Multiple Sclerosis

A Systematic Review

View ORCID ProfileMahdi Barzegar, Omid Mirmosayyeb, Mahsa Gajarzadeh, Alireza Afshari-Safavi, Nasim Nehzat, Saeed Vaheb, View ORCID ProfileVahid Shaygannejad, Amir-Hadi Maghzi
First published May 20, 2021, DOI: https://doi.org/10.1212/NXI.0000000000001001
Mahdi Barzegar
From the Department of Neurology (M.B., O.M., N.N., S.V., V.S.), School of Medicine, Isfahan University of Medical Sciences; Universal Council of Epidemiology (UCE) (M.G.), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences; Department of Biostatistics and Epidemiology (A.A.-S.), Faculty of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran; and Ann Romney Center for Neurologic Diseases (A.-H.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mahdi Barzegar
  • For correspondence: barzegar_mahdi73@yahoo.com
Omid Mirmosayyeb
From the Department of Neurology (M.B., O.M., N.N., S.V., V.S.), School of Medicine, Isfahan University of Medical Sciences; Universal Council of Epidemiology (UCE) (M.G.), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences; Department of Biostatistics and Epidemiology (A.A.-S.), Faculty of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran; and Ann Romney Center for Neurologic Diseases (A.-H.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: omid.mirmosayyeb@gmail.com
Mahsa Gajarzadeh
From the Department of Neurology (M.B., O.M., N.N., S.V., V.S.), School of Medicine, Isfahan University of Medical Sciences; Universal Council of Epidemiology (UCE) (M.G.), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences; Department of Biostatistics and Epidemiology (A.A.-S.), Faculty of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran; and Ann Romney Center for Neurologic Diseases (A.-H.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: m.ghajarzadeh@gmail.com
Alireza Afshari-Safavi
From the Department of Neurology (M.B., O.M., N.N., S.V., V.S.), School of Medicine, Isfahan University of Medical Sciences; Universal Council of Epidemiology (UCE) (M.G.), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences; Department of Biostatistics and Epidemiology (A.A.-S.), Faculty of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran; and Ann Romney Center for Neurologic Diseases (A.-H.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: alireza.afsharisafavi@gmail.com
Nasim Nehzat
From the Department of Neurology (M.B., O.M., N.N., S.V., V.S.), School of Medicine, Isfahan University of Medical Sciences; Universal Council of Epidemiology (UCE) (M.G.), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences; Department of Biostatistics and Epidemiology (A.A.-S.), Faculty of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran; and Ann Romney Center for Neurologic Diseases (A.-H.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: n.nehzat96@gmail.com
Saeed Vaheb
From the Department of Neurology (M.B., O.M., N.N., S.V., V.S.), School of Medicine, Isfahan University of Medical Sciences; Universal Council of Epidemiology (UCE) (M.G.), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences; Department of Biostatistics and Epidemiology (A.A.-S.), Faculty of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran; and Ann Romney Center for Neurologic Diseases (A.-H.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: saeedvaheb.sv@gmail.com
Vahid Shaygannejad
From the Department of Neurology (M.B., O.M., N.N., S.V., V.S.), School of Medicine, Isfahan University of Medical Sciences; Universal Council of Epidemiology (UCE) (M.G.), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences; Department of Biostatistics and Epidemiology (A.A.-S.), Faculty of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran; and Ann Romney Center for Neurologic Diseases (A.-H.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Vahid Shaygannejad
Amir-Hadi Maghzi
From the Department of Neurology (M.B., O.M., N.N., S.V., V.S.), School of Medicine, Isfahan University of Medical Sciences; Universal Council of Epidemiology (UCE) (M.G.), Universal Scientific Education and Research Network (USERN), Tehran University of Medical Sciences; Department of Biostatistics and Epidemiology (A.A.-S.), Faculty of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran; and Ann Romney Center for Neurologic Diseases (A.-H.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: amaghzi@bwh.harvard.edu
Full PDF
Citation
COVID-19 Among Patients With Multiple Sclerosis
A Systematic Review
Mahdi Barzegar, Omid Mirmosayyeb, Mahsa Gajarzadeh, Alireza Afshari-Safavi, Nasim Nehzat, Saeed Vaheb, Vahid Shaygannejad, Amir-Hadi Maghzi
Neurol Neuroimmunol Neuroinflamm Jul 2021, 8 (4) e1001; DOI: 10.1212/NXI.0000000000001001

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
2644

Share

See original article:

  • Errata - September 01, 2021
  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Abstract

Objective We systematically reviewed the literature on COVID-19 in patients with multiple sclerosis (MS).

Methods We searched PubMed, Scopus, EMBASE, CINAHL, Web of Science, Google Scholar, and World Health Organization database from December 1, 2019, to December 18, 2020. Three conference abstract databases were also searched. We included any types of studies that reported characteristics of patients with MS with COVID-19.

Results From an initial 2,679 publications and 3,138 conference abstracts, 87 studies (67 published articles and 20 abstracts) consisting of 4,310 patients with suspected/confirmed COVID-19 with MS met the inclusion criteria. The female/male ratio was 2.53:1, the mean (SD) age was 44.91 (4.31) years, the mean disease duration was 12.46 (2.27), the mean Expanded Disability Status Scale score was 2.54 (0.81), the relapsing/progressive ratio was 4.75:1, and 32.9% of patients had at least 1 comorbidity. The most common symptoms were fever (68.8%), followed by cough (63.9%), fatigue/asthenia (51.2%), and shortness of breath (39.5%). In total, 837 of 4,043 patients with MS with suspected/confirmed COVID-19 (20.7%) required hospitalization, and 130 of 4,310 (3.0%) died of COVID-19. Among suspected/confirmed patients, the highest hospitalization and mortality rates were in patients with no disease-modifying therapies (42.9% and 8.4%), followed by B cell–depleting agents (29.2% and 2.5%).

Conclusion Our study suggested that MS did not significantly increase the mortality rate from COVID-19. These data should be interpreted with caution as patients with MS are more likely female and younger compared with the general population where age and male sex seem to be risk factors for worse disease outcome.

Glossary

COVID-19=
coronavirus disease 2019;
DMT=
disease-modifying therapy;
EDSS=
Expanded Disability Status Scale;
MS=
multiple sclerosis;
PRISMA=
Preferred Reporting Items for Systematic Reviews and Meta-Analyses;
SARS-CoV-2=
severe acute respiratory syndrome coronavirus 2;
WHO=
World Health Organization

Multiple sclerosis (MS) is an inflammatory autoimmune disease of the CNS, which is a leading cause of disability in young adults. Most patients with MS are treated with immunomodulatory medications, which increase the risk of opportunistic infection, infection-related hospitalization, and infection-related mortality rates.1,-,4

The first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) was identified in Wuhan, China, on December 2019. After a rapid spread in China, new outbreaks occurred around almost all countries in the world. In March 2020, the World Health Organization (WHO) declared the outbreak of COVID-19 disease as a pandemic.5 As of December 22, 2020, a total of 75,129,306 confirmed cases and 1,680,794 fatalities were reported to the WHO worldwide.6

As coronavirus pandemic continues, a growing number of studies reported the clinical characteristics and outcomes of COVID-19 among patients with MS. However, there have been limited large observational studies investigating the symptoms, signs, complications, and outcome of COVID-19 in the MS population. The overall effects of COVID infection on MS and those on disease-modifying therapies (DMTs) remain unknown. To answer this question, we conducted this systematic review to bring together previous studies and provide an overall view of the published literature. The main goals of the current reviews are (1) to evaluate COVID infection outcomes in patients with MS (hospitalization/mortality), (2) to evaluate the effects of DMTs on these outcomes, and (3) to determine the clinical features and presentation of COVID-19 in patients with MS.

Methods

Literature Search

A comprehensive literature search was performed in PubMed, Scopus, EMBASE, CINAHL, Web of Science, Google Scholar, and WHO COVID-19 database. We screened the studies, which were published between December 1, 2019, and December 18, 2020. The following search strategy was adapted: ((coronavirus OR Wuhan coronavirus OR novel coronavirus OR coronavirus disease OR COVID-19 OR 2019 novel coronavirus infection OR 2019-nCOV OR severe acute respiratory syndrome coronavirus 2 OR SARS-CoV-2) AND (Multiple Sclerosis OR (Sclerosis, Multiple) OR (Sclerosis, Disseminated) OR Disseminated Sclerosis OR (Multiple Sclerosis, Acute Fulminating))). To identify potentially eligible studies that have not yet been published in full, we also searched abstracts available online from the following scientific meetings: Eighth American and European Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS-ECTRIMS 2020), 145th Annual Meeting American Neurological Association, and Sixth Congress of the European Academy of Neurology. Furthermore, we screened the reference lists of identified articles for inclusion in the study.

Inclusion and Exclusion Criteria

The inclusion criteria were as follows: (1) any type of studies including letters, case report, case series, cross-sectional, case-control, and cohort that reported COVID-19 among patients with MS and (2) written in English. The exclusion criteria were as follows: (1) not reporting outcome of patients with suspected or confirmed COVID-19, (2) preprint articles, (3) reviews, animal studies, hypothesis, and in vitro studies, and (4) articles reporting patients with Middle East respiratory syndrome–related coronavirus and SARS-CoV.

Study Selection

Two authors (M.B. and O.M.) independently screened, retrieved, and excluded reports. The reviewers screened the title and abstract of all retrieved articles. Both reviewers inspected the full text of all potential articles. Any disagreement over inclusion or exclusion of studies was resolved through feedback from a third reviewer (A.A.-S.).

Data Extraction

Data extraction was conducted by 2 reviewers (M.B. and S.V.) separately. The data were extracted from eligible articles including fist author's name, first publication date, location of study, type of study, number of patients with confirmed/suspected COVID-19, number of patients with positive PCR test, age, sex, Expanded Disability Status Scale (EDSS) score, disease duration, course of disease (relapsing-remitting MS, secondary progressive MS, primary progressive MS, and clinically isolated syndrome), DMT exposure, comorbidity (cardiovascular disease, diabetes mellitus, hypertension, chronic pulmonary diseases, malignancy, smoking status, obesity, and others), symptoms of COVID-19, and infection outcome (number of patients who hospitalized/number of death). This study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline.

Quality Assessment

Two reviewers (M.B. and N.N.) independently rated the quality of studies using the Newcastle-Ottawa Scale quality assessments.7 Based on studies design, different tools were used. Any disagreements were resolved by the senior reviewer (M.G.H.).

Outcomes

The primary outcome of the study was the assessment of clinical characteristics of COVID-19 among patients with MS. The secondary outcomes included assessment of hospitalization risk factors and proportion of patients required hospitalization, mortality rate, and relation to specific DMTs.

Data Presentation

We used descriptive analysis to report the results. Descriptive statistics were reported as mean ± SD for continuous variables and frequency (%) for categorical variables. Aggregated data were weighted by the number of patients and then combined with individual data. The proportion of patients with MS hospitalized and death among patients with suspected/confirmed COVID-19 with MS that reported in included studies were measured.

Results

Search Result

The PRISMA flowchart is shown in figure 1. A total of 2,679 articles were initially identified. After removal of duplicates, 2,175 articles remained. In the end, 67 published articles consisting of 1,739 suspected/confirmed patients met the inclusion criteria. Among 3,138 conference abstracts, a total of 20 abstracts reporting 2,571 patients with MS with suspected/confirmed COVID-19 were eligible for inclusion in the review. Totally, 87 studies consisting of 4,310 patients across 16 countries were included in our systematic review (figure e-1, links.lww.com/NXI/A476). The quality of evidence for each article is documented in table e-1 in appendix e-1.

Figure 1
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1 Flowchart of the Study

Study Characteristics

The characteristics of each study are presented in table e-2, links.lww.com/NXI/A476. In terms of study design, 48 (45 published articles and 3 abstracts) studies were case reports/series,8,9,e12-e54,e62-e64 4 (2 articles and 2 abstracts) were pharmacovigilance case series,10,11,e10,e11 18 (13 articles and 5 abstracts) were cross-sectional,12,-,18,e2-e9,e59-e61 and 17 (7 articles and 10 abstracts) were cohort studies.19,-,30,e1,e55-e58 Demographic and clinical characteristics of COVID-19 infection in patients are presented in table 1 and table e-3 in appendix e-1.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table 1

Demographic and Clinical Characteristics of COVID-19 Infection in Patients With MS

Presentation of COVID-19 in Patients With MS

The main clinical characteristics of COVID-19 among patients with MS were fever (68.8%), cough (63.9%), fatigue/asthenia (51.2%), shortness of breath (39.5%), headache (34.4%), and gastrointestinal complication (16.4%). Anosmia and ageusia were reported by 16.2% and 10.6% of patients, respectively. In total, only 70 asymptomatic patients with MS (of 1,312 cases; 5.3%) have been reported.

COVID Infection Outcomes in Patients With MS

The proportion of patients hospitalized to all suspected/confirmed cases was 20.7% (837 of 4,043 patients). Three published articles provided information on hospitalization risk factors.19,-,21 In these studies, hospitalization was more common among patients with older age, progressive course, and higher disability. Moreover, male sex,20,21 comorbidity,20,21 and obesity19,20 were more frequently present among hospitalized patients.

In total, 130 patients with MS (3.0% of all suspected/confirmed COVID-19 cases) died of COVID-19. The included articles and conference abstracts reported mortality rate of 2.2% (39 of 1,739 patients)8,9,12,14,-,16,19,-,22,24 and 3.5% (91 of 2,571 cases),10,11,17,18,25,-,30 respectively. The demographic and clinical characteristics of these patients are presented in table 2.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table 2

Characteristics of Patients Who Died of COVID-19

Effects of DMTs on COVID Infection Outcomes in Patients With MS

The most frequently used DMTs was B cell–depleting therapies (rituximab and ocrelizumab) in the entire cohort, followed by interferons, dimethyl fumarate, and fingolimod (table 1). The frequency of hospitalization in patients receiving B cell–depleting agents was 29.2% (117/400), 20.6% (13/63) in teriflunomide, 14.7% (18/122) in fingolimod, 14.5% (9/62) in glatiramer acetate, 13.9% (15/108) in dimethyl fumarate, 13.0% (10/77) in cladribine, 11.1% (2/18) in alemtuzumab, 11.0 (18/164) in interferon, and 10.1% (11/109) in natalizumab. Patients with no treatment had hospitalization rate of 42.9% (48/112).

The mortality rate among suspected/confirmed patients receiving B-cell depleting agents was 2.5% (12/488), 1.7% (4/241) in interferons, 1.6% (2/127) in teriflunomide, 1.1% (2/189) in natalizumab, 0.8% (1/117) in glatiramer acetate, 0.5% (1/192) in fingolimod, and 8.4% (24/285) in those on no DMT. Among patients who died of COVID-19 infection with their medication reported, no patients were on cladribine or alemtuzumab. The outcome of COVID-19 according to DMT class was summarized in table e-4, links.lww.com/NXI/A476.

Discussion

The aim of the current study was to determine the characteristics and outcome of COVID-19 infection in patients with MS. In this review, all studies in the literature, which assessed COVID-19 among MS that met the review criteria, were included. In total, our study consisted of 87 studies including 4,310 patients with MS with suspected/confirmed COVID-19 infection.

The frequency of asymptomatic individuals in the general population is estimated up to 45% of all infected cases.31 The low percentage (5.3%) of asymptomatic COVID-19 among patients with MS compared with the general population could be attributed to the fact that there are limited studies that have tested MS cohorts for antibodies to determine the rates of asymptomatic infection in this population. In total, 837 of 4,043 patients with MS with suspected/confirmed COVID-19 (20.7%) required hospitalization. The rate of hospitalization among patients with COVID-19 varies with age, sex, and presence of comorbidities.32,-,35 It is estimated that 1% of individuals younger than 20 years to about 20% of those aged 70 years or older would need hospitalization.32 Hospitalization rates also vary according to the location of the study, race, and phase of pandemic ranging from 2.9 to 30% of all COVID-19 cases.36,-,38 It seems that the hospitalization rates in patients with MS fall in the reported range for the general population; however, this has to be interpreted with caution as the demographic characteristics of patients with MS are generally younger and more female predominant than the general population, which should automatically put this cohort of patients at lower risks of hospitalization. Further studies are required to report outcomes after adjustment for variables that increase the rate of hospitalization in general population (e.g., age, sex, and race).

Among the included studies, 3 articles evaluated risk factors of hospitalization due to COVID-19 infection among the MS population.19,-,21 Older age, male sex, and having at least 1 comorbidity were independently associated with hospitalization among patients with MS, which are similar to risk factors observed in the general population.32,-,35 Patients with more disability as measured by the EDSS were at a higher risk of severe COVID-19 infection.20

The COVID-19 mortality rate among all suspected and confirmed cases with MS was 3.0%. The WHO reports that as of 22 December 2020, a total of 2.2% patients died of COVID-19 worldwide.6 The overall mortality rate of COVID-19 also differs between different countries, 1.8% in the United States, 2.2% in Europe, 4.6% in Iran, 2.6 in Brazil, and 2.8% in Chile.6 The mortality rate is less than 1% in individuals aged 20–60 years and increases exponentially (more than 10%) after 60 years.39,-,42 Of 42 patients with MS who died of COVID-19, 8 (19.1%) were younger than 50 years and 21 (50.0%) patients were older than 60 years. Fortunately, the overall mortality rates in the MS cohort remain low at 3.0% in general, but these rates are not adjusted for age, sex, and presence of comorbidities.

There is a significant concern about the impact of different DMTs on susceptibility and outcome of patients with MS with COVID-19. Several guidelines and recommendations from expert groups have been published.43,-,46 General agreement exists that treatment of patients with MS with interferon and glatiramer acetate does not increase the risk of severe COVID-19, and interferon preparations may be even protective. There is concern that higher-efficacy medications including S1P modulators, B cell–depleting therapies, alemtuzumab, and cladribine may increase the risk of severe COVID-19 in patients with MS. In a study investigating outcome of COVID-19 among French patients with MS, DMT use was not independently associated with COVID-19 severity.20 This was further supported by a study from New York, which showed no difference between hospitalized and non-hospitalized groups in the terms of DMT exposure.19 Moreover, it has been suggested that B-cell depletion agents, particularly rituximab,13,16 and cladribine/alemtuzumab23 may increase the risk of susceptibility to COVID-19. Evangelou et al.47 showed that patients with high efficacy therapies were less likely to have COVID-19 compared with those with no DMT.

After pooling all patients and calculating the hospitalization and mortality rates for each DMT, the highest hospitalization rate was in patients with no DMT (42.9%), followed by B cell–depleting agents (29.2%), teriflunomide (20.6%), and fingolimod (14.7%). The highest mortality rate was in patients with no DMTs (8.4%), followed by B-cell depletion agents (2.5%), interferon (1.7%), teriflunomide (1.6%), and natalizumab (1.1%). Although it may appear that patients on no DMTs have higher mortality and hospitalization rates, however, this is confounded by the general practice that older patients or those with advanced terminal stages of MS are usually not treated with DMT as the risk outweighs the benefit in this group of patients. The hospitalization and mortality rates among patients receiving B cell depleting are 2 times higher than other DMTs. However, given prior reports of potential increased risk of COVID-19 in patients treated with B-cell therapies, the high hospitalization and mortality rates in this group should be studied in more details. It could be argued that high hospitalization rate of teriflunomide may be due to small number of reported patients. The hospitalization and mortality rates of DMTs therefore need to be interpreted with caution. Almost all patients with MS who died of COVID-19 were at high risk for developing severe COVID-19 because of age, comorbidity, or severe MS disability. Taken together, based on the current literature and small number of fatalities, it seems that MS may not dramatically increase the mortality rate from COVID-19.

Diagnosis of COVID-19 in 763 (of 2,173) patients with MS (35.1%) was confirmed by PCR; however we cannot determine the seropositivity among patients with MS because most suspected patients were not tested for the presence of antibodies. There are some similarities and differences between clinical features of COVID-19 reported by studies on MS and those described among the general population.48,49 Fever was the most common symptoms among patients with MS and the general population.48,-,50 The prevalence of cough, shortness of breath/dyspnea in 63% and 39.5% among infected patients with MS with COVID-19 is broadly similar to those identified in other studies on the general population.51 The pooled incidence of fatigue among all patients with COVID-19 is reported to be 46%,49,51 which is lower than of 51.2% reported in patients with MS. This difference may be explained by the fact that fatigue is one of the most common symptoms among patients with MS, and nearly 75% of the patients report fatigue during the disease and infections could worsen this symptom.52

Our study has several limitations. First, a meta-analysis was not possible due to heterogeneity of studies. Second, it has been suggested that a significant proportion of individuals developed asymptomatic and mild COVID-19, but most patients in this study are symptomatic or admitted to a hospital. Although it remains unknown what percentage of patients with MS develop asymptomatic infection, it is possible that severe COVID-19 is overrepresented in the published literature, and the findings could not be extrapolated to the whole MS population. Third, most of the studies included are case reports/series or based on a small sample of participants. Fourth, without large multicentric studies and results from local and global COVID-19 data data sets,53 the effect of DMTs on susceptibility and severity of COVID-19 remains unknown. Fifth, articles not published in English and not report clinical information of patients with COVID-19 were excluded, so some studies on the subject may not have been identified. Sixth, we cannot ascertain the incidence of COVID-19 among patients with MS. Population-based studies are needed to determine the true incidence of COVID-19 among patients with MS. Seventh, conference abstracts included inadequate data, and the validity of the results is questionable without proper peer review. However, inclusion of abstracts minimizes publication bias and provides more data that were not available in published format at the time of publication of this work.

In conclusion, our systematic review comprehensively detailed the demographic and clinical characteristics of patients with MS with COVID-19 published to date. Fortunately, the severity and mortality from COVID-19 in patients with MS does not seem to be significantly higher than the general population. However, further larger studies are needed to study this topic closer with adjustments for COVID-19 risk factors. Use of DMTs seems to be generally safe with no significant increased risk of poor COVID-19 outcomes; however, there may be a signal for B cell–depleting therapies slightly worsening COVID-19 infection.

Study Funding

No targeted funding reported.

Disclosure

The authors report no disclosures relevant to the manuscript. Go to Neurology.org/NN for full disclosures.

Appendix Authors

Table

Footnotes

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • The Article Processing Charge was funded by Neurology® Neuroimmunology & Neuroinflammation.

  • Received October 6, 2020.
  • Accepted in final form February 5, 2021.
  • Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

References

  1. 1.↵
    1. Wijnands JM,
    2. Kingwell E,
    3. Zhu F, et al
    . Infection-related health care utilization among people with and without multiple sclerosis. Mult Scler J 2017;23:1506–1516.
    OpenUrl
  2. 2.↵
    1. Epstein DJ,
    2. Dunn J,
    3. Deresinski S
    . Infectious complications of multiple sclerosis therapies: implications for screening, prophylaxis, and management. Open Forum Infect Dis 2018;5:ofy174.
    OpenUrlCrossRef
  3. 3.↵
    1. Montgomery S,
    2. Hillert J,
    3. Bahmanyar S
    . Hospital admission due to infections in multiple sclerosis patients. Eur J Neurol 2013;20:1153–1160.
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Nelson RE,
    2. Xie Y,
    3. DuVall SL, et al
    . Multiple sclerosis and risk of infection-related hospitalization and death in US veterans. Int J MS Care 2015;17:221–230.
    OpenUrl
  5. 5.↵
    OWorld Health Organization. Coronavirus Disease (COVID-19) Outbreak. Accessed September 18, 2020. who.int
  6. 6.↵
    World Health Organization. Situation reports. Weekly epidemiological update; 22 December 2020. Accessed December 26, 2020. who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports
  7. 7.↵
    1. Stang A
    . Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603–605.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Bowen JD,
    2. Brink J,
    3. Brown TR, et al
    . COVID-19 in MS: initial observations from the Pacific Northwest. Neurol Neuroimmunol Neuroinflamm 2020;7:e783.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Rimmer K,
    2. Farber R,
    3. Thakur K, et al
    . Fatal COVID-19 in an MS patient on natalizumab: a case report. Mult Scler J Exp Transl Clin 2020;6:2055217320942931.
    OpenUrl
  10. 10.↵
    1. Freedman MGH,
    2. Murgasova Z,
    3. Jack D
    . Post-approval safety of subcutaneous interferon β-1a in the treatment of multiple sclerosis, with particular reference to respiratory viral infections. Presented at the 8th ACTRIMS-ECTRIMS; December 1, 2020; Washington (virtual).
  11. 11.↵
    1. Reder AAA,
    2. Wicklein EM,
    3. Bhatti A
    . Use and safety of interferon beta-1b during the COVID-19 outbreak: current data from a pharmacovigilance safety database. Presented at the 8th ACTRIMS-ECTRIMS; December 1, 2020; Washington (virtual).
  12. 12.↵
    1. Sormani MP
    . An Italian programme for COVID-19 infection in multiple sclerosis. Lancet Neurol 2020;19:481–482.
    OpenUrlCrossRef
  13. 13.↵
    1. Safavi F,
    2. Nourbakhsh B,
    3. Azimi AR
    . B-cell depleting therapies may affect susceptibility to acute respiratory illness among patients with multiple sclerosis during the early COVID-19 epidemic in Iran. Mult Scler Relat Disord 2020;43:102195.
    OpenUrl
  14. 14.↵
    1. Barzegar M,
    2. Mirmosayyeb O,
    3. Ghajarzadeh M, et al
    . Characteristics of COVID-19 disease in multiple sclerosis patients. Mult Scler Relat Disord 2020;45:102276.
    OpenUrl
  15. 15.↵
    1. Álvarez FC,
    2. Pérez MÁL,
    3. Sola MEM
    . Risk of SARS-CoV-2 infection and clinical outcomes in multiple sclerosis patients in La Rioja (Spain). Med Clin (Barc) 2020;155:362–363.
    OpenUrl
  16. 16.↵
    1. Sahraian MA,
    2. Azimi A,
    3. Navardi S,
    4. Ala S,
    5. Moghadasi AN
    . Evaluation of the rate of COVID-19 infection, hospitalization and death among Iranian patients with multiple sclerosis. Mult Scler Relat Disord 2020;46:102472.
    OpenUrl
  17. 17.↵
    1. Kieseier B,
    2. Rajbhandari R,
    3. Altincatal A, et al
    . COVID-19 and multiple sclerosis—prevalence and the impact of disease modifying therapies. Presented at the 8th ACTRIMS-ECTRIMS; December 1, 2020; Washington (virtual).
  18. 18.↵
    1. Poursadeghfard M BM,
    2. Borhani Haghighi A,
    3. Molavi Vardanjani H,
    4. Fayyazpoor A,
    5. Salehi D
    . Descriptive data analysis of COVID-19 among patients with multiple sclerosis; a cross-sectional study of southern Iran. Presented at the 8th ACTRIMS-ECTRIMS; December 1, 2020; Washington (virtual).
  19. 19.↵
    1. Parrotta E,
    2. Kister I,
    3. Charvet L, et al
    . COVID-19 outcomes in MS: observational study of early experience from NYU Multiple Sclerosis Comprehensive Care Center. Neurol Neuroimmunol Neuroinflamm 2020;7:e835.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Louapre C,
    2. Collongues N,
    3. Stankoff B, et al
    . Clinical characteristics and outcomes in patients with coronavirus disease 2019 and multiple sclerosis. JAMA Neurol 2020;77:1079–1088.
    OpenUrl
  21. 21.↵
    1. Loonstra FC,
    2. Hoitsma E,
    3. van Kempen ZL,
    4. Killestein J,
    5. Mostert JP
    . COVID-19 in multiple sclerosis: the Dutch experience. Mult Scler J 2020;26:1256–1260.
    OpenUrl
  22. 22.↵
    1. Chaudhry F,
    2. Bulka H,
    3. Rathnam AS, et al
    . COVID-19 in multiple sclerosis patients and risk factors for severe infection. J Neurol Sci 2020;418:117147.
    OpenUrlPubMed
  23. 23.↵
    1. Dalla Costa G,
    2. Leocani L,
    3. Montalban X, et al
    . Real-time assessment of COVID-19 prevalence among multiple sclerosis patients: a multicenter European study. Neurol Sci 2020;41:1647–1650.
    OpenUrl
  24. 24.↵
    1. Kovvuru S,
    2. Nalleballe K,
    3. Onteddu SR, et al
    . Immunosuppression in chronic autoimmune neurological disorders during the COVID-19 pandemic. J Neurol Sci 2021:420:117230.
    OpenUrl
  25. 25.↵
    1. Moreno-Torres I,
    2. Meca-Lallana V,
    3. Costa-Frossard L
    . Risk and outcomes of COVID-19 in patients with multiple sclerosis in Madrid Spain. Presented at the 8th ACTRIMS-ECTRIMS; December 1, 2020; Washington (virtual).
  26. 26.↵
    1. Zabalza A,
    2. Tagliani P,
    3. Cárdenas-Robledo S
    . COVID-19 in MS patients: susceptibility and severity risk factors. Presented at the 8th ACTRIMS-ECTRIMS; December 1, 2020; Washington (virtual).
  27. 27.↵
    1. Klineova S,
    2. Harel A,
    3. Straus Farber R
    . COVID-19 infection in patients with multiple sclerosis: an observational study by the New York COVID-19 Neuroimmunology Consortium (NYCNIC). Presented at the 8th ACTRIMS-ECTRIMS; December 1, 2020; Washington (virtual).
  28. 28.↵
    1. Mendes MF,
    2. Ferreira ML,
    3. Sousa NA
    . Incidence and clinical outcome of COVID-19 in a cohort of 11.560 Brazilian patients with multiple sclerosis. Presented at the 8th ACTRIMS-ECTRIMS; December 1, 2020; Washington (virtual).
  29. 29.↵
    1. Salter A,
    2. Halper J,
    3. Bebo B
    . COViMS Registry: clinical characterization of SARS-CoV-2 infected multiple sclerosis patients in North America. Presented at the 8th ACTRIMS-ECTRIMS; December 1, 2020; Washington (virtual).
  30. 30.↵
    1. Dillon P WA,
    2. Roumpanis S,
    3. Martinec M,
    4. Muros-Le Rouzic E
    . A real-world data study of coronavirus-2019 disease severity in patients with multiple sclerosis treated with ocrelizumab. Presented at the 8th ACTRIMS-ECTRIMS; December 1, 2020; Washington (virtual).
  31. 31.↵
    1. Oran DP,
    2. Topol EJ
    . Prevalence of asymptomatic SARS-CoV-2 infection: a narrative review. Ann Intern Med 2020;173:362–367.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Clark A,
    2. Jit M,
    3. Warren-Gash C, et al
    . Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study. Lancet Glob Health 2020;8:e1003–e1017.
    OpenUrlCrossRefPubMed
  33. 33.↵
    1. Garg S
    . Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019—COVID-NET, 14 States, March 1–30, 2020. MMWR Morb Mortal Wkly Rep 2020;69:458–464.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Salje H,
    2. Kiem CT,
    3. Lefrancq N, et al
    . Estimating the burden of SARS-CoV-2 in France. Science 2020;369:208–211.
    OpenUrlAbstract/FREE Full Text
  35. 35.↵
    1. Verity R,
    2. Okell LC,
    3. Dorigatti I, et al
    . Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis 2020;20:669–677.
    OpenUrlCrossRefPubMed
  36. 36.↵
    ECDC. Coronavirus disease 2019 (COVID-19) pandemic: increased transmission in the EU/EEA and the UK—seventh update. Published Online First: March 25, 2020. Accessed September 21, 2020. ecdc.europa.eu/sites/default/files/documents/RRA-seventh-update-Outbreak-of-coronavirus-disease-COVID-19.pdf
  37. 37.↵
    1. Price-Haywood EG,
    2. Burton J,
    3. Fort D,
    4. Seoane L
    . Hospitalization and mortality among black patients and white patients with COVID-19. N Engl J Med 2020;382:2534–2543.
    OpenUrlCrossRefPubMed
  38. 38.↵
    Coronavirus disease 2019 (COVID-19): Epidemiology update. Updated: September 20, 2020. Accessed September 21, 2020. health-infobase.canada.ca/covid-19/epidemiological-summary-covid-19-cases.html
  39. 39.↵
    1. Bonanad C,
    2. García-Blas S,
    3. Tarazona-Santabalbina F, et al
    . The effect of age on mortality in patients with COVID-19: a meta-analysis with 611,583 subjects. J Am Med Dir Assoc 2020;21:915–918.
    OpenUrlCrossRefPubMed
  40. 40.↵
    1. Onder G,
    2. Rezza G,
    3. Brusaferro S
    . Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA 2020;323:1775–1776.
    OpenUrlPubMed
  41. 41.↵
    1. Perez-Saez J,
    2. Lauer SA,
    3. Kaiser L, et al
    . Serology-informed estimates of SARS-CoV-2 infection fatality risk in Geneva, Switzerland. medRxiv 2020.
  42. 42.↵
    1. Russell TW,
    2. Hellewell J,
    3. Jarvis CI, et al
    . Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020. Eurosurveillance 2020;25:2000256.
    OpenUrl
  43. 43.↵
    1. Berger JR,
    2. Brandstadter R,
    3. Bar-Or A
    . COVID-19 and MS disease-modifying therapies. Neurol Neuroimmunol Neuroinflamm 2020;7:e761.
    OpenUrlAbstract/FREE Full Text
  44. 44.↵
    1. Korsukewitz C,
    2. Reddel SW,
    3. Bar-Or A,
    4. Wiendl H
    . Neurological immunotherapy in the era of COVID-19—looking for consensus in the literature. Nat Rev Neurol 2020;16:493–505.
    OpenUrl
  45. 45.↵
    1. Brownlee W,
    2. Bourdette D,
    3. Broadley S,
    4. Killestein J,
    5. Ciccarelli O
    . Treating multiple sclerosis and neuromyelitis optica spectrum disorder during the COVID-19 pandemic. Neurology 2020;94:949–952.
    OpenUrl
  46. 46.↵
    1. Giovannoni G,
    2. Hawkes C,
    3. Lechner-Scott J,
    4. Levy M,
    5. Waubant E,
    6. Gold J
    . The COVID-19 pandemic and the use of MS disease-modifying therapies. Mult Scler Relat Disord 2020;39:102073.
    OpenUrl
  47. 47.↵
    1. Evangelou N,
    2. Garjani A,
    3. Hunter R, et al
    . Self-diagnosed COVID-19 in people with multiple sclerosis: a community-based cohort of the UK MS Register. J Neurol Neurosurg Psychiatry 2020;92:107–109.
    OpenUrl
  48. 48.↵
    1. Li LQ,
    2. Huang T,
    3. Wang YQ, et al
    . COVID‐19 patients' clinical characteristics, discharge rate, and fatality rate of meta‐analysis. J Med Virol 2020;92:577–583.
    OpenUrlCrossRefPubMed
  49. 49.↵
    1. Fu L,
    2. Wang B,
    3. Yuan T, et al
    . Clinical characteristics of coronavirus disease 2019 (COVID-19) in China: a systematic review and meta-analysis. J Infect 2020;80:656–665.
    OpenUrlCrossRefPubMed
  50. 50.↵
    1. Richardson S,
    2. Hirsch JS,
    3. Narasimhan M, et al
    . Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020;323:2052–2059.
    OpenUrlCrossRefPubMed
  51. 51.↵
    1. Zhu J,
    2. Ji P,
    3. Pang J, et al
    . Clinical characteristics of 3,062 COVID‐19 patients: a meta‐analysis. J Med Virol 2020;92:1902–1914.
    OpenUrlCrossRefPubMed
  52. 52.↵
    1. Braley TJ,
    2. Chervin RD
    . Fatigue in multiple sclerosis: mechanisms, evaluation, and treatment. Sleep 2010;33:1061–1067.
    OpenUrlPubMed
  53. 53.↵
    1. Peeters LM,
    2. Parciak T,
    3. Walton C, et al
    . COVID-19 in people with multiple sclerosis: a global data sharing initiative. Mult Scler J 2020;26:1157–1162.
    OpenUrl

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • Glossary
    • Methods
    • Results
    • Discussion
    • Study Funding
    • Disclosure
    • Appendix Authors
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

SARS-CoV-2 Vaccination Safety in Guillain-Barré Syndrome, Chronic Inflammatory Demyelinating Polyneuropathy, and Multifocal Motor Neuropathy

Dr. Jeffrey Allen and Dr. Nicholas Purcell

► Watch

Related Articles

  • COVID-19 Among Patients With Multiple SclerosisA Systematic Review

Topics Discussed

  • Multiple sclerosis
  • COVID-19

Alert Me

  • Alert me when eletters are published

Recommended articles

  • Article
    SARS-CoV-2 Infection in Multiple Sclerosis
    Results of the Spanish Neurology Society Registry
    Georgina Arrambide, Miguel Ángel Llaneza-González, Lucienne Costa-Frossard França et al.
    Neurology: Neuroimmunology & Neuroinflammation, June 24, 2021
  • Article
    A New England COVID-19 Registry of Patients With CNS Demyelinating Disease
    A Pilot Analysis
    Kelli M. Money, Ashmanie Mahatoo, Soleil Samaan et al.
    Neurology: Neuroimmunology & Neuroinflammation, August 02, 2021
  • Article
    COVID-19 in Patients With Neuromyelitis Optica Spectrum Disorders and Myelin Oligodendrocyte Glycoprotein Antibody Disease in North America
    From the COViMS Registry
    Scott D. Newsome, Anne H. Cross, Robert J. Fox et al.
    Neurology: Neuroimmunology & Neuroinflammation, August 24, 2021
  • Article
    Incidence and Impact of COVID-19 in MS
    A Survey From a Barcelona MS Unit
    Maria Sepúlveda, Sara Llufriu, Eugenia Martínez-Hernández et al.
    Neurology: Neuroimmunology & Neuroinflammation, January 27, 2021
Neurology - Neuroimmunology Neuroinflammation: 10 (3)

Articles

  • Articles
  • Issues
  • Popular Articles

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology: Neuroimmunology & Neuroinflammation
Online ISSN: 2332-7812

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise