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Background: Interferon-β, a disease-modifying therapy (DMT) for MS, may be associated with less severe COVID-19 in people with MS., Results: Among 5,568 patients (83.4% confirmed COVID-19), interferon-treated patients had lower risk of severe COVID-19 compared to untreated, but not to glatiramer-acetate, dimethyl-fumarate, or pooled other DMTs., Conclusions: In comparison to other DMTs, we did not find evidence of protective effects of interferon-β on the severity of COVID-19, though compared to the untreated, the course of COVID19 was milder among those on interferon-β. This study does not support the use of interferon-β as a treatment to reduce COVID-19 severity in MS., Competing Interests: Declaration of Competing Interest Steve Simpson-Yap has no conflicts of interests to disclose. Ashkan Pirmani has no conflicts of interests to disclose. Edward De Brouwer has no conflicts of interests to disclose. Liesbet M. Peeters has no personal pecuniary interests to disclose, other than being the chair of The MS Data Alliance (MSDA), which received income from a range of corporate sponsors, recently including Biogen, BristolMyersSquibb (formerly Celgene), Janssen Pharmaceuticals, Merck, Novartis, QMENTA, and Roche. Lotte Geys has no other conflicts of interests to disclose than that she is funded by the Flemish Government under the “Onderzoeksprogramma Artificiële Intelligentie Vlaanderen”. Tina Parciak has no conflicts of interests to disclose. Anne Helme has no personal pecuniary interests to disclose, other than being an employee of the MS International Federation, which receives income from a range of corporate sponsors, recently including: Biogen, BristolMyersSquibb, Janssen, Sanofi, Merck, Mylan, Novartis, and Roche – all of which is publicly disclosed. Jan Hillert has received honoraria for serving on advisory boards for Biogen, Celgene, Sanofi-Genzyme, Merck KGaA, Novartis and Sandoz and speaker's fees from Biogen, Novartis, Merck KGaA, Teva and Sanofi-Genzyme, has served as principal investigator for projects, or received unrestricted research support from Biogen, Celgene, Merck KGaA, Novartis, Roche and Sanofi-Genzyme, and his MS research was funded by the Swedish Research Council and the Swedish Brain foundation. Yves Moreau has no conflicts of interests to disclose. Gilles Edan has received consulting/speaking fees and research support from Bayer, Novartis, Teva, Sanofi Genzyme, Merck Serono, Biogen Idec, and Roche. Tim Spelman served on scientific advisory boards for Biogen. Sifat Sharmin has no conflicts of interests to disclose. Robert McBurney works for the Accelerated Cure Project for MS (ACP), which has received grants, collaboration funding, payments for use of assets, or in-kind contributions from the following companies: EMD Serono, Sanofi/Genzyme, Biogen, Genentech, AbbVie, Octave, GlycoMinds, Pfizer, MedDay, AstraZeneca, Teva, Mallinckrodt, MSDx, Regeneron Genetics Center, BC Platforms, and Celgene. ACP has also received funding from the Patient-Centered Outcomes Research Institute (PCORI) and the National MS Society (NMSS). RMcB. has received consulting payments from EMD Serono, which have been donated to ACP. Hollie Schmidt works for the Accelerated Cure Project for MS (ACP), which has received grants, collaboration funding, payments for use of assets, or in-kind contributions from the following companies: EMD Serono, Sanofi/Genzyme, Biogen, Genentech, AbbVie, Octave, GlycoMinds, Pfizer, MedDay, AstraZeneca, Teva, Mallinckrodt, MSDx, Regeneron Genetics Center, BC Platforms, and Celgene. ACP has also received funding from the Patient-Centered Outcomes Research Institute (PCORI) and the National MS Society (NMSS). Arnfin Bergmann has received consulting fees from and is an advisory board/speaker/other activities for NeuroTransData, and has worked on project management/clinical studies for and received travel expenses from Novartis and Servier. Stefan Braune receives fees for consulting, clinical studies and lectures from NeuroTransData, Novartis, Celgene, Biogen, CSl Behring. Alexander Stahmann has no personal pecuniary interests to disclose, other than being the lead of the German MS-Registry, which receives (project) funding from a range of public and corporate sponsors, recently including The German Innovation Fund (G-BA), The German MS Trust, Biogen, German MS Society, Celgene (BMS), Merck, Novartis, Roche, and Sanofi. Rodden Middleton has received no personal funding from any sources, the UK MS Register is funded by the MS Society and has received funding for specific projects from Novartis, Sanofi-Genzyme and Merck KGaA. Amber Salter is on the editorial board for Neurology and received research funding from the Department of Defense, National MS Society and the Consortium of MS Centers. Bruce Bebo has no conflicts of interests to disclose. Anneke van der Walt has received honoraria and unrestricted research funding from Novartis, Biogen, Roche, Merck and Sanofi. Helmut Butzkueven's institution receives compensation for Advisory Board, Steering Committee and Educational activities from Biogen, Roche, Merck, and Novartis. His-institution receives research support from Roche, Novartis, Biogen, NHMRC and MRFF Australia, MS Research Australia and the Trish MS Foundation. He receives personal compensation from Oxford HPF for serving on the steering group of MS Brain Health. Serkan Ozakabas has no conflicts of interests to disclose. Rana Karabudak has received honoraria for educational lectures, consultancy fees for participating advisory boards, and travel grants for attending scientific congresses or symposia from Roche, Sanofi-Genzyme, Merck-Serono, Novartis, Teva, Biogen Idec/Gen Pharma of Turkey, Abdi İbrahim İlaç, Deva and ARIS. Cavit Boz received conference travel support from Biogen, Novartis, Roche, Merck and Teva, and has participated in clinical trials by Sanofi Aventis, Roche and Novartis. Raed Alroughani has received honoraria as a speaker and for serving in scientific advisory boards from Bayer, Novartis, Roche, Sanofi, Merck and Biogen. Juan I Rojas has received honoraria from Novartis as a scientific advisor, and has received travel grants and attended courses and conferences on behalf of Merck-Serono Argentina, Novartis Argentina. Ingrid van der Mei has no conflicts of interests to disclose. Guilherme Sciascia do Olival has no relevant conflicts of interests to disclose. Melinda Magyari has served on scientific advisory board for Biogen, Sanofi, Roche, Novartis, Merck, Abbvie, has received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, and has received research support and support for congress participation from Biogen, Genzyme, Roche, Merck, Novartis. Ricardo Alonso has received honoraria from Novartis as a scientific advisor, travel grants and attended courses and conferences on behalf of Merck-Serono Argentina, Biogen Argentina, Genzyme Argentina, Roche Argentina and Novartis Argentina. Richard Nicholas has received honoraria from Novartis, Roche and Biogen for advisory boards. Anibal Chertcoff has no conflicts of interests to disclose. Ana Zabalza has received travel expenses for scientific meetings from Biogen, Novartis, and Genzyme, speaking honoraria from Eisai, and a study grant from Novartis. Georgina Arrambide has received compensation for consulting services or participation in advisory boards from Sanofi, Merck and Roche, research support from Novartis, travel expenses for scientific meetings from Novartis, Roche, Stendhal, and ECTRIMS, speaking honoraria from Sanofi and Merck, and is a member of the International Women in Multiple Sclerosis (iWiMS) network executive committee. Nupur Nag has no conflicts of interests to disclose. Annabel Descamps has no conflicts of interests to disclose. Lars Costers has no conflicts of interests to disclose. Ruth Dobson has participated in advisory boards for Merck, Biogen, Janssen, Novartis and Roche. Grant support from Biogen, Merck and Celgene. Aleisha Miller has no conflicts of interests to disclose. Paulo Rodrigues is a shareholder, employee and member of board of directors of QMENTA. Vesna Prchkovska is a shareholder, employee and member of board of directors of QMENTA. Giancarlo Comi has received consulting and speaking fees from Novartis, Teva Pharmaceutical Industries Ltd, Teva Italia Srl, Sanofi Genzyme, Genzyme Corporation, Genzyme Europe, Merck KGgA, Merck Serono SpA, Celgene Group, Biogen Idec, Biogen Italia Srl, F. Hoffman-La Roche, Roche SpA, Almirall SpA, Forward Pharma, Medday and Excemed. Tomas Kalincik has served on scientific advisory boards for Roche, Sanofi-Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi-Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi-Genzyme, Teva, BioCSL and Merck and received research support from Biogen., (Copyright © 2022 Elsevier B.V. All rights reserved.)