The impact of COVID-19 infection on multiple sclerosis disease course across 12 countries: a propensity-score-matched cohort study

David Levitz; Yi Chao Foong; Paul Sanfilippo; Tim Spelman; Louise Rath; Angie Roldan; Anoushka Lal; Mastura Monif; Vilija Jokubaitis; Serkan Ozakbas; Raed Alroughani; Cavit Boz; Murat Terzi; Tomas Kalincik; Yolanda Blanco; Matteo Foschi; Andrea Surcinelli; Katherine Buzzard; Olga Skibina; Guy Laureys; Liesbeth Van Hijfte; Cristina Ramo-Tello; Aysun Soysal; Jose Luis Sanchez-Menoyo; Mario Habek; Elisabetta Cartechini; Juan Ignacio Rojas; Rana Karabudak; Barbara Willekens; Talal Al-Harbi; Yara Fragoso; Tamara Castillo-Triviño; Danny Decoo; Maria Cecilia Aragon de Vecino; Eli Skromne; Carmen-Adella Sirbu; Chao Zhu; Daniel Merlo; Melissa Gresle; Helmut Butzkueven; Anneke Van Der Walt

doi:10.1177/17562864241278496

The impact of COVID-19 infection on multiple sclerosis disease course across 12 countries: a propensity-score-matched cohort study

Ther Adv Neurol Disord. 2024 Nov 7:17:17562864241278496. doi: 10.1177/17562864241278496. eCollection 2024.

Authors

David Levitz¹, Yi Chao Foong^{1

2}, Paul Sanfilippo¹, Tim Spelman³, Louise Rath¹, Angie Roldan¹, Anoushka Lal¹, Mastura Monif¹, Vilija Jokubaitis¹, Serkan Ozakbas⁴, Raed Alroughani⁵, Cavit Boz⁶, Murat Terzi⁷, Tomas Kalincik^{8

9}, Yolanda Blanco¹⁰, Matteo Foschi^{11

12}, Andrea Surcinelli¹¹, Katherine Buzzard^{13

14}, Olga Skibina^{2

13

14}, Guy Laureys¹⁵, Liesbeth Van Hijfte¹⁵, Cristina Ramo-Tello¹⁶, Aysun Soysal¹⁷, Jose Luis Sanchez-Menoyo^{18

19}, Mario Habek^{20

21}, Elisabetta Cartechini²², Juan Ignacio Rojas²³, Rana Karabudak²⁴, Barbara Willekens^{25

26}, Talal Al-Harbi²⁷, Yara Fragoso²⁸, Tamara Castillo-Triviño²⁹, Danny Decoo³⁰, Maria Cecilia Aragon de Vecino³¹, Eli Skromne³², Carmen-Adella Sirbu^{33

34}, Chao Zhu¹, Daniel Merlo¹³, Melissa Gresle¹, Helmut Butzkueven^{1

2}, Anneke Van Der Walt^{35

2}

Affiliations

¹ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC, Australia.
² Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia.
³ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
⁴ Dokuz Eylul University, Konak, Turkey.
⁵ Division of Neurology, Department of Medicine, Amiri Hospital, Kuwait City, Kuwait.
⁶ KTU Medical Faculty Farabi Hospital, Trabzon, Turkey.
⁷ Medical Faculty, 19 Mayis University, Samsun, Turkey.
⁸ Neuroimmunology Centre, Department of Neurology, The Royal Melbourne Hospital, Melbourne, VIC, Australia.
⁹ CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
¹⁰ Center of Neuroimmunology, Service of Neurology, Hospital Clinic de Barcelona, Barcelona, Spain.
¹¹ Department of Neuroscience, Neurology Unit, S. Maria delle Croci Hospital of Ravenna, AUSL Romagna, Ravenna, Italy.
¹² Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, L'Aquila, Italy.
¹³ Department of Neurology, Box Hill Hospital, Melbourne, VIC, Australia.
¹⁴ Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.
¹⁵ Department of Neurology, University Hospital Ghent, Ghent, Belgium.
¹⁶ Hospital Germans Trias i Pujol, Badalona, Spain.
¹⁷ Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey.
¹⁸ Hospital de Galdakao-Usansolo, Galdakao, Spain.
¹⁹ Instituto de Investigacion sanitario Biocruces-Bizkaia, Barakaldo, Spain.
²⁰ Department of Neurology, University Hospital Center Zagreb, Zagreb, Croatia.
²¹ School of Medicine, University of Zagreb, Zagreb, Croatia.
²² UOC Neurologia, Azienda Sanitaria Unica Regionale Marche - AV3, Macerata, Italy.
²³ Hospital Universitario de CEMIC, Buenos Aires, Argentina.
²⁴ Hacettepe University, Ankara, Turkey.
²⁵ Department of Neurology, Antwerp University Hospital, Edegem, Belgium.
²⁶ Translational Neurosciences Research Group, Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium.
²⁷ King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia.
²⁸ Universidade Metropolitana de Santos, Santos, Brazil.
²⁹ Hospital Universitario Donostia and IIS Biodonostia, San Sebastián, Spain.
³⁰ AZ Alma Ziekenhuis, Damme, Belgium.
³¹ Hospital Moinhos de Vento, Porto Alegre, Brazil.
³² Hospital Angeles de las Lomas, Instituto Mexicano de Neurociencias, Huixquilucan, Mexico.
³³ Central Military Emergency University Hospital, Bucharest, Romania.
³⁴ Titu Maiorescu University, Bucharest, Romania.
³⁵ Department of Neuroscience, Central Clinical School, Monash University, 99 Commercial Road, Melbourne, VIC 3004, Australia.

Abstract

Background: The relationship between coronavirus disease 2019 (COVID-19) infection and multiple sclerosis (MS) relapse and disease progression remains unclear. Previous studies are limited by small sample sizes and most lack a propensity-matched control cohort.

Objective: To evaluate the effect of COVID-19 infection on MS disease course with a large propensity-matched cohort.

Design: This multi-centre cohort study analysed relapse and disability outcomes post-COVID-19 infection after balancing covariates using a propensity score matching method. The study period was from the 11th of September 2019 to the 16th of February 2023. The mean follow-up period was 1.7 years.

Methods: Data were retrieved from the MSBase Registry. Propensity scores were obtained based on age, sex, disease duration, baseline Expanded Disability Status Scale (EDSS), MS course, relapses pre-baseline, disease-modifying therapy (DMT) class and country. Primary outcomes were time to first relapse, annualised relapse rate (ARR) and time to confirm EDSS progression. Secondary outcomes were time to EDSS of 3, 4 or 6. Sensitivity analyses with baseline DMT classes were performed.

Results: The study included 2253 cases and 6441 controls. After matching, there were 2161 cases and an equal number of matched controls. Cases had a significantly higher ARR (ARR = 0.10 [95% CI 0.09-0.11]) compared to controls (ARR = 0.07 [95% CI 0.06-0.08]). Cases had a significantly greater hazard of time to first relapse compared to controls (hazard ratio (HR) = 1.54 [95% CI 1.29-1.84]). There was no association between COVID-19 infection and 24-week EDSS progression (HR = 1.18 [95% CI 0.92-1.52]), or time to EDSS of 3, 4 or 6. For patients on interferons and glatiramer acetate (BRACE), COVID-19 infection was associated with a greater hazard of time to first relapse (HR = 1.83 [95% CI 1.25-2.68]) and greater hazard of time to EDSS of 3 (HR = 2.04 [95% CI 1.06-3.90]) compared to patients on BRACE therapy without COVID-19 infection.

Conclusion: COVID-19 infection was associated with a significantly increased MS relapse rate and a shorter time to first relapse. There was no effect on confirmed EDSS progression over the short term. These results support ongoing COVID-19 risk minimisation strategies to protect patients with MS.

Keywords: COVID-19; disease progression; multiple sclerosis; relapse.