Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • 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
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • 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

September 2020; 7 (5) Clinical/Scientific NotesOpen Access

Should interferons take front stage as an essential MS disease-modifying therapy in the era of coronavirus disease 2019?

Cole Maguire, Teresa Frohman, Scott S. Zamvil, Elliot Frohman, Esther Melamed
First published June 11, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000811
Cole Maguire
From the Department of Neurology (C.M., T.F., E.F., E.M.), Dell Medical School, Austin, TX; and Department of Neurology and Program in Immunology (S.S.Z.), University of California, San Francisco, CA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Teresa Frohman
From the Department of Neurology (C.M., T.F., E.F., E.M.), Dell Medical School, Austin, TX; and Department of Neurology and Program in Immunology (S.S.Z.), University of California, San Francisco, CA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott S. Zamvil
From the Department of Neurology (C.M., T.F., E.F., E.M.), Dell Medical School, Austin, TX; and Department of Neurology and Program in Immunology (S.S.Z.), University of California, San Francisco, CA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elliot Frohman
From the Department of Neurology (C.M., T.F., E.F., E.M.), Dell Medical School, Austin, TX; and Department of Neurology and Program in Immunology (S.S.Z.), University of California, San Francisco, CA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Esther Melamed
From the Department of Neurology (C.M., T.F., E.F., E.M.), Dell Medical School, Austin, TX; and Department of Neurology and Program in Immunology (S.S.Z.), University of California, San Francisco, CA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
Should interferons take front stage as an essential MS disease-modifying therapy in the era of coronavirus disease 2019?
Cole Maguire, Teresa Frohman, Scott S. Zamvil, Elliot Frohman, Esther Melamed
Neurol Neuroimmunol Neuroinflamm Sep 2020, 7 (5) e811; DOI: 10.1212/NXI.0000000000000811

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
593

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

In the unprecedented pandemic of the coronavirus disease 2019 (COVID-19) along with a limited clinical understanding on effective vaccines and therapies, there are currently many unknowns for patients with autoimmune conditions, such as MS, who require ongoing treatment with immunotherapies. As information is currently lacking on the immune effects of COVID-19 in the context of MS disease-modifying therapies (DMTs), a challenging clinical question being faced by patients and neurologists is whether to continue current DMTs for patients with MS and risk potentially greater morbidity and mortality due to COVID-19 infection vs discontinue DMT therapy and risk MS disease relapse. At this time, we desperately need data to guide which DMTs may best treat both COVID-19 and MS.

Impressively, there has been a rapid international medical response in repurposing several antiviral therapies toward COVID-19 treatment, including remdesivir, lopinavir, ritonavir, ribavirin, interferon-alpha (IFN-α), and interferon-beta (IFN-β)1,2 (NCT04315948). Type I interferons such as IFN-β are of particular interest for patients with MS because these DMTs have been Food and Drug Administration-approved for use in MS since the 1990s.3 Interferons were originally discovered to “interfere” with viral replication and are classified as type I (IFN-α, β, and ω), type II (IFN-γ), or type III. In the human IFN-α family, there are 13 genes encoding several isoforms, many of which have been popularized for treatment. By contrast, human IFN-β is encoded by only 2 genes with a more limited number of commercially available recombinant isoforms. Between the type I interferons, IFN-β has been primarily used in MS, whereas IFN-α has been commonly used in the treatment of viral infections, such as herpes zoster, hepatitis B and C, and HIV. However, there is also evidence to suggest that IFN-α may have beneficial effects in MS. For example, treatment with IFN-α2a can lead to a reduction in MRI disease activity in patients with MS with neutralizing antibodies to IFN-β.4

Different IFN-α and IFN-β isoforms are currently being evaluated and compared for the treatment of COVID-19. Interferon signaling pathways seem to be significantly upregulated, especially during the most critical stages of pulmonary disease, with IFN-α serum levels correlating with disease severity during the peak of disease.5,6 Similarly, circulating IFN-β has also been reported to increase during peak disease stages although IFN-β levels remain elevated even after symptomatic improvement.5,6 These data suggest that IFN-α may have a key role in the reduction of the viral load during the peak of the COVID-19 disease, whereas IFN-β may have a potential role in the reduction of viral replication over the entire course of the disease. Because interferons are known to induce different cytokines and genes in different cell types and organs, one important caveat to consider is the timing of interferon administration in COVID-19 and the possibility of dichotomous interferon effects during early vs later stages of the disease.

IFN-α has already been used as an active treatment for COVID-19 in China.1 Both nebulized and subcutaneous forms of recombinant IFN-α, IFN-β1a, and IFN-β1b are also currently tested in COVID-19 clinical trials in combination with other therapeutics (NCT04315948, NCT04276688, NCT04293887, NCT04251871, and NCT04275388).

One of the largest current trials, the World Health Organization multinational SOLIDARITY trial, is currently evaluating 4 therapeutic regiments including (1) IFN-β with ritonavir/lopinavir, (2) ritonavir/lopinavir without IFN-β, (3) chloroquine or hydroxychloroquine, and (4) remdesivir.2 Of note, nebulized preparation of IFN-α has been reported to improve delivery to the respiratory tract while also reducing common interferon side effects, such as fatigue and myalgias, symptoms that can also be a part of COVID-19 infection.

Although interferon therapies revolutionized MS management in the 1990s, more recently, interferons have been relegated to the backstage of the MS DMT armamentarium because of the emergence of more effective and better tolerated DMTs. Nevertheless, given the potential benefits of interferons in the treatment of COVID-19, an important question now is whether interferons should be again brought to the front stage of MS management. If data from ongoing clinical trials continue to support the benefit of interferons in the treatment of COVID-19, it is perhaps prudent to consider interferons as a first-line therapy in newly diagnosed patients with MS. In patients with MS on other DMTs, we could consider changing therapy to interferons or adding interferon therapy to the patient's current DMT. For patients with active MS, other potential treatment strategies may be to combine interferon therapy with pulsed intermittent corticosteroids or IV immunoglobulin given monthly to quarterly or with a DMT that has antiviral properties (e.g., teriflunomide7). In the latter case, a carefully formulated treatment plan tailored to the patient could provide a strategic advantage over cell depleting MS DMTs by virtue of the inherent multiplicity of actions of type I IFNs when used as part of combination therapy.

There are of course many unknowns regarding whether IFN-β or IFN-α therapies would be effective in the management of COVID-19 and MS and which specific IFN-β and IFN-α isoforms may best create this balance. It will also be important to continue to assess how treatments such as IVIG and steroids may impact MS and COVID-19. Furthermore, treatment decisions will vary depending on patient age, disease activity, comorbidities, and current DMT. Nevertheless, based on the long-standing clinical experience and long-term safety profile of IFN-β use in patients with MS, interferons could be a critical therapy to treat both COVID-19 and MS during the unprecedented international pandemic, and we should reconsider interferons' place in the MS DMT armamentarium.

Study funding

This work was supported by the University of Texas Dell Medical School Start Up funding to E. Melamed. The corresponding author, E. Melamed, had the final responsibility for the decision to submit this manuscript for publication.

Disclosure

None to report. Go to Neurology.org/NN for full disclosures.

Acknowledgment

The authors thank Dr. William Schwartz for critical reading of the manuscript.

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 the authors.

  • Received April 19, 2020.
  • Accepted in final form May 12, 2020.
  • Copyright © 2020 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. Dong L,
    2. Hu S,
    3. Gao J
    . Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discoveries Ther 2020;14:58–60.
    OpenUrl
  2. 2.↵
    1. Kupferschmidt K,
    2. Cohen J
    . WHO launches global megatrial of the four most promising coronavirus treatments [online]. Science; 2020. Available at: https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments. Accessed March 30, 2020.
  3. 3.↵
    1. Axtell RC,
    2. Steinman L
    . Type 1 interferons cool the inflamed brain. Immunity 2008;28:600–602.
    OpenUrlPubMed
  4. 4.↵
    1. Myhr K,
    2. Riise T,
    3. Lilleås FG, et al
    . Interferon-α2a reduces MRI disease activity in relapsing-remitting multiple sclerosis. Neurology 1999;52:1049.
    OpenUrlCrossRef
  5. 5.↵
    1. Huang L,
    2. Shi Y,
    3. Gong B, et al
    . Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19. medRxiv 2020.03.15.20033472; doi: 10.1101/2020.03.15.20033472.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Wei L,
    2. Ming S,
    3. Zou B, et al
    . Viral invasion and type I interferon response characterize the immunophenotypes during COVID-19 infection. CELL-D-20-00887. Available at SSRN: https://ssrn.com/abstract=3564998 or http://dx.doi.org/10.2139/ssrn.3564998.
  7. 7.↵
    1. Gilli F,
    2. Li L,
    3. Royce DB,
    4. DiSano KD,
    5. Pachner AR
    . Treatment of Theiler's virus-induced demyelinating disease with teriflunomide. J Neurovirol 2017;23:825–838.
    OpenUrl

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.

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
    • Study funding
    • Disclosure
    • Acknowledgment
    • Appendix Authors
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials

Dr. Nicole Sur and Dr. Mausaminben Hathidara

► Watch

Related Articles

  • No related articles found.

Topics Discussed

  • All Immunology
  • All Clinical trials
  • Multiple sclerosis
  • COVID-19

Alert Me

  • Alert me when eletters are published

Recommended articles

  • Article
    COVID-19 and MS disease-modifying therapies
    Joseph R. Berger, Rachel Brandstadter, Amit Bar-Or et al.
    Neurology: Neuroimmunology & Neuroinflammation, May 15, 2020
  • Editor's Corner
    N2 year in review
    Josep Dalmau, Marinos C. Dalakas, Dennis L. Kolson et al.
    Neurology: Neuroimmunology & Neuroinflammation, December 18, 2020
  • 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 (4)

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