BACKGROUND: COVID-19 vaccination and infection are speculated to increase the activity of immune-mediated diseases, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The aim of this study was to evaluate a short-term risk of relapse after COVID-19 vaccination and COVID-19 infection in patients with these demyelinating disorders of the central nervous system and to determine disease exacerbation risk factors. METHODS: Data in this retrospective, observational cohort study was collected via the Czech nationwide registry ReMuS from March 1, 2020, to October 30, 2021. We compared the proportion of patients with at least one clinical relapse in the 90 days following vaccination or infection to the 90-day intervals during the year before. For the evaluation of the risk factors of relapse, a comparison between groups with and without relapses after COVID-19 vaccination or infection was made. RESULTS: We identified 1661 vaccinated (90.11% BNT162b2) patients with MS without a history of COVID-19 and 495 unvaccinated patients with MS who experienced COVID-19. A mild increase in the proportion of patients with at least one clinical relapse (-360 to -270 days: 4.46%; -270 to -180: 4.27%; -180 to -90: 3.85%; -90 to 0: 3.79% vs. 0 to +90 days: 5.30%) after vaccination in patients with MS was observed, as well as a rise in the proportion of patients with at least one clinical relapse after COVID-19. Lower age was associated with MS relapse after vaccination or infection. Although there were only 17 vaccinated and eight post-COVID-19 patients with NMOSD, the results were broadly consistent with those of patients with MS. CONCLUSION: There is a mild increase in the relapse incidence after the COVID-19 vaccination. The risks, however, need to be balanced against the risks of COVID-19 itself, also leading to the rise in relapse rate and particularly to morbidity and mortality.

Department of Neurology and Centre of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czechia

Department of Neurology and Centre of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czechia; 2nd Department of Neurology Faculty of Medicine Comenius University Bratislava Slovakia

Department of Neurology and Centre of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czechia; Department of Neurology KZ a s Hospital Teplice Teplice Czechia

Department of Neurology and Centre of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czechia; Endowment Fund IMPULS Prague Czechia

Mult Scler Relat Disord. 2022 Sep;65:104102. doi: 10.1016/j.msard.2022.104102. PubMed

Mult Scler Relat Disord. 2023 Feb;70:104549. doi: 10.1016/j.msard.2023.104549. PubMed

Zobrazit více v PubMed

Achiron A., Dolev M., Menascu S., Zohar D.N., Dreyer-Alster S., Miron S., Shirbint E., Magalashvili D., Flechter S., Givon U., Guber D., Stern Y., Polliack M., Falb R., Gurevich M. COVID-19 vaccination in patients with multiple sclerosis: what we have learnt by February 2021. Mult. Scler. 2021;27:864–870. doi: 10.1177/13524585211003476. PubMed DOI PMC

Aly A.S., Alkolfat F., Mansour E.R., Salama S. Guillain-Barre syndrome following COVID-19 vaccination: a case report and an updated review. Neuroimmunol. Reports. 2022;2 doi: 10.1016/J.NEREP.2022.100083. DOI

Baden L.R., el Sahly H.M., Essink B., Kotloff K., Frey S., Novak R., Diemert D., Spector S.A., Rouphael N., Creech C.B., McGettigan J., Khetan S., Segall N., Solis J., Brosz A., Fierro C., Schwartz H., Neuzil K., Corey L., Gilbert P., Janes H., Follmann D., Marovich M., Mascola J., Polakowski L., Ledgerwood J., Graham B.S., Bennett H., Pajon R., Knightly C., Leav B., Deng W., Zhou H., Han S., Ivarsson M., Miller J., Zaks T. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 2021;384:403–416. doi: 10.1056/NEJMOA2035389. PubMed DOI PMC

Barzegar M., Mirmosayyeb O., Ebrahimi N., Bagherieh S., Afshari-Safavi A., Hosseinabadi A.M., Shaygannejad V., Asgari N. COVID-19 susceptibility and outcomes among patients with neuromyelitis optica spectrum disorder (NMOSD): a systematic review and meta-analysis. Mult. Scler. Relat. Disord. 2021 doi: 10.1016/j.msard.2021.103359. PubMed DOI PMC

Barzegar M., Vaheb S., Mirmosayyeb O., Afshari-Safavi A., Nehzat N., Shaygannejad V. Can coronavirus disease 2019 (COVID-19) trigger exacerbation of multiple sclerosis? A retrospective study. Mult. Scler. Relat. Disord. 2021;52 doi: 10.1016/J.MSARD.2021.102947. PubMed DOI PMC

Cai H., Zhou R., Jiang F., Zeng Q., Yang H. Vaccination in neuromyelitis optica spectrum disorders: friend or enemy? Mult. Scler. Relat. Disord. 2021 doi: 10.1016/J.MSARD.2021.103394. PubMed DOI

Confavreux C., Suissa S., Saddier P., Bourdès V., Vukusic S. Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group. N. Engl. J. Med. 2001;344:319–326. doi: 10.1056/NEJM200102013440501. PubMed DOI

Correale J., Fiol M., Gilmore W. The risk of relapses in multiple sclerosis during systemic infections. Neurology. 2006;67:652–659. doi: 10.1212/01.WNL.0000233834.09743.3B. PubMed DOI

di Filippo M., Cordioli C., Malucchi S., Annovazzi P., Cavalla P., Torri Clerici V., Ragonese P., Nociti V., Radaelli M., Laroni A., Buttari F., Lorefice L., Ferraro D., Gajofatto A., Prosperini L., Fantozzi R., Boffa L., Lanzillo R., Moccia M., Clerico M., de Luca G., Tomassini V., Calabrese M., Borrelli A., Paolicelli D., Maniscalco G.T., Gazzola P., Gallo A., Solaro C., Cocco E., Gasperini C., Tortorella C. 2021. mRNA COVID-19 vaccines do not increase the short-term risk of clinical relapses in multiple sclerosis. J Neurology, Neurosurg Psychiatry jnnp. 2021 doi: 10.1136/jnnp-2021-327200. PubMed DOI

Dinoto A., Sechi E., Ferrari S., Gajofatto A., Orlandi R., Solla P., Maccabeo A., Maniscalco G.T., Andreone V., Sartori A., Manganotti P., Rasia S., Capra R., Mancinelli C.R., Mariotto S. Risk of disease relapse following COVID-19 vaccination in patients with AQP4-IgG-positive NMOSD and MOGAD. Mult. Scler. Relat. Disord. 2021 doi: 10.1016/J.MSARD.2021.103424. PubMed DOI PMC

Etemadifar M., Sedaghat N., Aghababaee A., Kargaran P.K., Maracy M.R., Ganjalikhani-Hakemi M., Rayani M., Abhari A.P., Khorvash R., Salari M., Nouri H. COVID-19 and the risk of relapse in multiple sclerosis patients: a fight with no bystander effect? Mult. Scler. Relat. Disord. 2021;51 doi: 10.1016/J.MSARD.2021.102915. PubMed DOI PMC

Fragoso Y.D., Gomes S., Gonçalves M.V.M., Mendes Junior E., Oliveira B.E.S.de, Rocha C.F., Santos G.A.C.dos, Tauil C.B., Araujo R.V., Peron J.P.S. New relapse of multiple sclerosis and neuromyelitis optica as a potential adverse event of AstraZeneca AZD1222 vaccination for COVID-19. Mult. Scler. Relat. Disord. 2021 doi: 10.1016/J.MSARD.2021.103321. PubMed DOI PMC

Horakova, D., 2021. Doporučení Výboru Sekce klinické neuroimunologie a likvorologie ČNS ČLS JEP [WWW Document]. URL https://www.czech-neuro.cz/content/uploads/2021/03/2021_3_6-dh-doporuceni-update.pdf (accessed 1.22.22).

Horakova D., Rockova P., Jircikova J., Dolezal T., Vachova M., Hradilek P., Valis M., Sucha J., Martinkova A., Ampapa R., Grunermelova M., Stetkarova I., Stourac P., Mares J., Dufek M., Kmetova E., Adamkova J., Hrnciarova T. Initiation of first disease-modifying treatment for multiple sclerosis patients in the Czech republic from 2013 to 2016: data from the national registry ReMuS. Mult. Scler. Relat. Disord. 2019;35:196–202. doi: 10.1016/J.MSARD.2019.08.003. PubMed DOI

Jovicevic V., Ivanovic J., Andabaka M., Tamas O., Veselinovic N., Momcilovic N., Mesaros S., Pekmezovic T., Drulovic J. COVID-19 and vaccination against SARS-CoV-2 in patients with neuromyelitis optica spectrum disorders. Mult. Scler. Relat. Disord. 2021 doi: 10.1016/J.MSARD.2021.103320. PubMed DOI PMC

Kim J.E., Min Y.G., Shin J.Y., Kwon Y.N., Bae J.S., Sung J.J., Hong Y.H. Guillain–Barré syndrome and variants following COVID-19 vaccination: report of 13 Cases. Front Neurol. 2022;12:2636. doi: 10.3389/FNEUR.2021.820723/BIBTEX. PubMed DOI PMC

Lee G.M., Greene S.K., Weintraub E.S., Baggs J., Kulldorff M., Fireman B.H., Baxter R., Jacobsen S.J., Irving S., Daley M.F., Yin R., Naleway A., Nordin J.D., Li L., McCarthy N., Vellozzi C., Destefano F., Lieu T.A. H1N1 and seasonal influenza vaccine safety in the Vaccine Safety datalink Project. Am. J. Prev. Med. 2011;41:121–128. doi: 10.1016/J.AMEPRE.2011.04.004/ATTACHMENT/29AFE14A-359C-4B25-9DEE-B1B986E9A127/MMC1.PDF. PubMed DOI

Li X., Gao L., Tong X., Chan V.K.Y., Chui C.S.L., Lai F.T.T., Wong C.K.H., Wan E.Y.F., Chan E.W.Y., Lau K.K., Lau C.S., Wong I.C.K. Autoimmune conditions following mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccination: a descriptive cohort study among 1.1 million vaccinated people in Hong Kong. J. Autoimmun. 2022;130 doi: 10.1016/J.JAUT.2022.102830. PubMed DOI PMC

Lotan I., Romanow G., Levy M. Patient-reported safety and tolerability of the COVID-19 vaccines in persons with rare neuroimmunological diseases. Mult. Scler. Relat. Disord. 2021;55 doi: 10.1016/J.MSARD.2021.103189. PubMed DOI PMC

Lotan I., Wilf-Yarkoni A., Friedman Y., Stiebel-Kalish H., Steiner I., Hellmann M.A. Safety of the BNT162b2 COVID-19 vaccine in multiple sclerosis (MS): early experience from a tertiary MS center in Israel. Eur. J. Neurol. 2021;28:3742–3748. doi: 10.1111/ENE.15028. PubMed DOI PMC

Ma X., Kermode A.G., Hu X., Qiu W. Risk of relapse in patients with neuromyelitis optica spectrum disorder: recognition and preventive strategy. Mult. Scler. Relat. Disord. 2020;46 doi: 10.1016/J.MSARD.2020.102522. PubMed DOI

Meo S.A., Bukhari I.A., Akram J., Meo A.S., Klonoff D.C. COVID-19 vaccines: comparison of biological, pharmacological characteristics and adverse effects of Pfizer/BioNTech and Moderna Vaccines. Eur. Rev. Med. Pharmacol. Sci. 2021;25:1663–1679. doi: 10.26355/EURREV_202102_24877. PubMed DOI

Müller L., di Benedetto S., Pawelec G. The immune system and its dysregulation with aging. Subcell. Biochem. 2019;91:21–43. doi: 10.1007/978-981-13-3681-2_2. PubMed DOI

Polack F.P., Thomas S.J., Kitchin N., Absalon J., Gurtman A., Lockhart S., Perez J.L., Pérez Marc G., Moreira E.D., Zerbini C., Bailey R., Swanson K.A., Roychoudhury S., Koury K., Li P., Kalina W.v., Cooper D., Frenck R.W., Hammitt L.L., Türeci Ö., Nell H., Schaefer A., Ünal S., Tresnan D.B., Mather S., Dormitzer P.R., Şahin U., Jansen K.U., Gruber W.C. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 2020;383:2603–2615. doi: 10.1056/NEJMOA2034577. PubMed DOI PMC

Prosperini L., Tortorella C., Haggiag S., Ruggieri S., Galgani S., Gasperini C. Determinants of COVID-19-related lethality in multiple sclerosis: a meta-regression of observational studies. J. Neurol. 2022;(1):1–11. doi: 10.1007/S00415-021-10951-6. 2022. PubMed DOI PMC

Sadighi Akha A.A. Aging and the immune system: an overview. J. Immunol. Methods. 2018;463:21–26. doi: 10.1016/J.JIM.2018.08.005. PubMed DOI

Sadoff J., Gray G., Vandebosch A., Cárdenas V., Shukarev G., Grinsztejn B., Goepfert P.A., Truyers C., Fennema H., Spiessens B., Offergeld K., Scheper G., Taylor K.L., Robb M.L., Treanor J., Barouch D.H., Stoddard J., Ryser M.F., Marovich M.A., Neuzil K.M., Corey L., Cauwenberghs N., Tanner T., Hardt K., Ruiz-Guiñazú J., le Gars M., Schuitemaker H., van Hoof J., Struyf F., Douoguih M. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N. Engl. J. Med. 2021;384:2187–2201. doi: 10.1056/NEJMOA2101544. PubMed DOI PMC

Stastna D., Menkyova I., Drahota J., Mazouchova A., Adamkova J., Ampapa R., Grunermelova M., Peterka M., Recmanova E., Rockova P., Rous M., Stetkarova I., Valis M., Vachova M., Woznicova I., Horakova D. Multiple sclerosis, neuromyelitis optica spectrum disorder and COVID-19: a pandemic year in Czechia. Mult. Scler. Relat. Disord. 2021;54 doi: 10.1016/J.MSARD.2021.103104. PubMed DOI PMC

Uher T., Krasensky J., Malpas C., Bergsland N., Dwyer M.G., Kubala Havrdova E., Vaneckova M., Horakova D., Zivadinov R., Kalincik T. Evolution of brain volume loss rates in early stages of multiple sclerosis. Neurol. - Neuroimmunol. Neuroinflammation. 2021;8 doi: 10.1212/NXI.0000000000000979. PubMed DOI PMC

Voysey M., Clemens S.A.C., Madhi S.A., Weckx L.Y., Folegatti P.M., Aley P.K., et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet North Am. Ed. 2021;397:99–111. doi: 10.1016/S0140-6736(20)32661-1/ATTACHMENT/BD910DFE-2C8A-4512-A277-6B1DBA6322EE/MMC2.PDF. PubMed DOI PMC

Watad A., de Marco G., Mahajna H., Druyan A., Eltity M., Hijazi N., Haddad A., Elias M., Zisman D., Naffaa M.E., Brodavka M., Cohen Y., Abu-Much A., Elhija M.A., Bridgewood C., Langevitz P., McLorinan J., Bragazzi N.L., Marzo-Ortega H., Lidar M., Calabrese C., Calabrese L., Vital E., Shoenfeld Y., Amital H., McGonagle D. Immune-mediated disease flares or new-onset disease in 27 subjects following mRNA/DNA SARS-CoV-2 vaccination. Vaccines (Basel) 2021;9 doi: 10.3390/VACCINES9050435. PubMed DOI PMC

The Czech National MS Registry (ReMuS): Data trends in multiple sclerosis patients whose first disease-modifying therapies were initiated from 2013 to 2021

COVID-19 vaccination and relapse activity: A nationwide cohort study of patients with multiple sclerosis in Denmark

Immunity following SARS-CoV-2 vaccination in autoimmune neurological disorders treated with rituximab or ocrelizumab