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      SARS-CoV-2 vaccination and multiple sclerosis: a large multicentric study on relapse risk after the third booster dose

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      1 , , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 1 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 17 , 18 , 19 , 20 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 4 , 4 , the RIREMS (Rising Researchers in MS) group
      Journal of Neurology
      Springer Berlin Heidelberg
      COVID-19, SARS-CoV-2, Vaccination, Multiple sclerosis

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          Abstract

          Background

          COVID-19 vaccines have been recommended to people with multiple sclerosis (pwMS) and, to ensure durable immunity, a third booster dose has been administered in several countries. Data about potential risks associated with the third booster dose in pwMS, such as vaccine-triggered disease exacerbations, are still scarce.

          Objective

          To investigate whether the administration of a third booster dose of mRNA COVID-19 vaccines was associated with an increased risk of short-term disease reactivation in a large cohort of pwMS.

          Methods

          We retrospectively selected 1265 pwMS who received a third booster dose of an mRNA COVID-19 vaccine. Demographic and clinical data were collected, including the presence, number and characteristics of relapses in the 60 days prior to and after the third booster dose.

          Results

          In the selected cohort, the relapse rate in the two months after administration of the third booster dose of mRNA COVID-19 vaccines did not increase when compared with the prior two months. Indeed, the percentage of pwMS experiencing relapses in the 60 days following the administration of the third booster dose was 2.1%, similar to the percentage recorded in 60 days prior to vaccination, which was 1.9%.

          Conclusions

          The third booster dose of mRNA COVID-19 vaccines appeared to be safe for pwMS.

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          Most cited references28

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          Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria

          The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.
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            Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months

            Background Despite high vaccine coverage and effectiveness, the incidence of symptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been increasing in Israel. Whether the increasing incidence of infection is due to waning immunity after the receipt of two doses of the BNT162b2 vaccine is unclear. Methods We conducted a 6-month longitudinal prospective study involving vaccinated health care workers who were tested monthly for the presence of anti-spike IgG and neutralizing antibodies. Linear mixed models were used to assess the dynamics of antibody levels and to determine predictors of antibody levels at 6 months. Results The study included 4868 participants, with 3808 being included in the linear mixed-model analyses. The level of IgG antibodies decreased at a consistent rate, whereas the neutralizing antibody level decreased rapidly for the first 3 months with a relatively slow decrease thereafter. Although IgG antibody levels were highly correlated with neutralizing antibody titers (Spearman’s rank correlation between 0.68 and 0.75), the regression relationship between the IgG and neutralizing antibody levels depended on the time since receipt of the second vaccine dose. Six months after receipt of the second dose, neutralizing antibody titers were substantially lower among men than among women (ratio of means, 0.64; 95% confidence interval [CI], 0.55 to 0.75), lower among persons 65 years of age or older than among those 18 to less than 45 years of age (ratio of means, 0.58; 95% CI, 0.48 to 0.70), and lower among participants with immunosuppression than among those without immunosuppression (ratio of means, 0.30; 95% CI, 0.20 to 0.46). Conclusions Six months after receipt of the second dose of the BNT162b2 vaccine, humoral response was substantially decreased, especially among men, among persons 65 years of age or older, and among persons with immunosuppression.
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              Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel

              Background On July 30, 2021, the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech) was approved in Israel for persons who were 60 years of age or older and who had received a second dose of vaccine at least 5 months earlier. Data are needed regarding the effect of the booster dose on the rate of confirmed coronavirus 2019 disease (Covid-19) and the rate of severe illness. Methods We extracted data for the period from July 30 through August 31, 2021, from the Israeli Ministry of Health database regarding 1,137,804 persons who were 60 years of age or older and had been fully vaccinated (i.e., had received two doses of BNT162b2) at least 5 months earlier. In the primary analysis, we compared the rate of confirmed Covid-19 and the rate of severe illness between those who had received a booster injection at least 12 days earlier (booster group) and those who had not received a booster injection (nonbooster group). In a secondary analysis, we evaluated the rate of infection 4 to 6 days after the booster dose as compared with the rate at least 12 days after the booster. In all the analyses, we used Poisson regression after adjusting for possible confounding factors. Results At least 12 days after the booster dose, the rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of 11.3 (95% confidence interval [CI], 10.4 to 12.3); the rate of severe illness was lower by a factor of 19.5 (95% CI, 12.9 to 29.5). In a secondary analysis, the rate of confirmed infection at least 12 days after vaccination was lower than the rate after 4 to 6 days by a factor of 5.4 (95% CI, 4.8 to 6.1). Conclusions In this study involving participants who were 60 years of age or older and had received two doses of the BNT162b2 vaccine at least 5 months earlier, we found that the rates of confirmed Covid-19 and severe illness were substantially lower among those who received a booster (third) dose of the BNT162b2 vaccine.
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                Author and article information

                Contributors
                massimiliano.difilippo@unipg.it
                Journal
                J Neurol
                J Neurol
                Journal of Neurology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-5354
                1432-1459
                3 November 2023
                3 November 2023
                2024
                : 271
                : 1
                : 24-31
                Affiliations
                [1 ]Clinica Neurologica, Dipartimento di Medicina e Chirurgia, Università di Perugia, ( https://ror.org/00x27da85) Perugia, Umbria Italy
                [2 ]GRID grid.413363.0, ISNI 0000 0004 1769 5275, Dipartimento di Neuroscienze, , Ospedale Civile di Baggiovara, Azienda Ospedaliera-Università di Modena, ; Modena, Italy
                [3 ]Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata, Università degli Studi di Palermo, ( https://ror.org/044k9ta02) Palermo, Italy
                [4 ]GRID grid.416308.8, ISNI 0000 0004 1805 3485, Dipartimento di Neuroscienze, , Ospedale San Camillo-Forlanini, ; Rome, Italy
                [5 ]GRID grid.413172.2, Centro Regionale Sclerosi Multipla, Dipartimento di Neurologia e Stroke Unit, , Ospedale “A. Cardarelli”, ; Naples, Italy
                [6 ]Dipartimento di Scienze Mediche e Chirurgiche Avanzate, Università degli Studi Della Campania Luigi Vanvitelli, ( https://ror.org/02kqnpp86) Naples, Italy
                [7 ]GRID grid.432329.d, ISNI 0000 0004 1789 4477, Centro Sclerosi Multipla e Neurologia 1 D.U, Dipartimento di Neuroscienze e Salute Mentale, , Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, ; Turin, Italy
                [8 ]Centro Sclerosi Multipla, Dipartimento di Scienze Mediche e di Sanità Pubblica, ASL Cagliari, Università di Cagliari, ( https://ror.org/003109y17) Ospedale Binaghi, Cagliari, Italy
                [9 ]GRID grid.8142.f, ISNI 0000 0001 0941 3192, Centro Sclerosi Multipla, , Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, ; Rome, Italy
                [10 ]Dipartimento di Scienze Cliniche e Biologiche dell’Università di Torino, AOU San Luigi Gonzaga Di Orbassano, Orbassano, Italy
                [11 ]Neurologia ad Indirizzo Neuroimmunologico-Centro Sclerosi Multipla, ASST Valle Olona, Gallarate, Italy
                [12 ]GRID grid.460094.f, ISNI 0000 0004 1757 8431, U.O.C. Di Neurologia, ASST Papa Giovanni XXIII, ; Bergamo, Italy
                [13 ]Unità Di Neurologia, IRCCS Neuromed, ( https://ror.org/00cpb6264) Pozzilli, Italy
                [14 ]GRID grid.6530.0, ISNI 0000 0001 2300 0941, Dipartimento di Medicina dei Sistemi, , Università di Tor Vergata, ; Rome, Italy
                [15 ]Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica, Scienze Materno-Infantili, Università di Genova, ( https://ror.org/0107c5v14) Genoa, Italy
                [16 ]IRCCS Ospedale Policlinico San Martino, ( https://ror.org/04d7es448) Genoa, Italy
                [17 ]GRID grid.5611.3, ISNI 0000 0004 1763 1124, Dipartimento di Neuroscienze, Biomedicina e Movimento, , Università di Verona, ; Verona, Italy
                [18 ]SCDO Neurologia – CRESM, AOU San Luigi Gonzaga, Orbassano, Italy
                [19 ]Dipartimento di Biomedicina Traslazionale e Neuroscienze, Università degli Studi di Bari Aldo Moro, ( https://ror.org/027ynra39) Bari, Italy
                [20 ]Centro Sclerosi Multipla, Clinica Neurologica, Ospedale Universitario SS Annunziata, Chieti, Italy
                [21 ]Istituto di Tecnologie Avanzate Biomediche (ITAB), Dipartimento di Neuroscienze, Imaging e Scienze Cliniche, Facoltà di Medicina e Chirurgia, Università di Chieti-Pescara “G. D’Annunzio”, ( https://ror.org/00qjgza05) Chieti, Italy
                [22 ]GRID grid.4691.a, ISNI 0000 0001 0790 385X, Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, , Università Degli Studi Federico II, ; Naples, Italy
                [23 ]Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, ( https://ror.org/05290cv24) Naples, Italy
                [24 ]GRID grid.4691.a, ISNI 0000 0001 0790 385X, Centro Sclerosi Multipla, , Ospedale Universitario Federico II, ; Naples, Italy
                [25 ]GRID grid.450697.9, ISNI 0000 0004 1757 8650, Unità di Neurologia, E.O. Ospedali Galliera, ; Genoa, Italy
                [26 ]GRID grid.7763.5, ISNI 0000 0004 1755 3242, Dipartimento di Scienze Mediche e Sanità Pubblica, , Centro Regionale Sclerosi Multipla, ASL Cagliari, ATS Sardegna, Università di Cagliari, ; Cagliari, Italy
                Author information
                http://orcid.org/0000-0002-2645-7477
                Article
                12034
                10.1007/s00415-023-12034-0
                10769943
                37922069
                fe5e15dc-ebb4-4468-a7c9-5b3225625990
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 7 July 2023
                : 26 September 2023
                : 28 September 2023
                Funding
                Funded by: Università degli Studi di Perugia
                Categories
                Original Communication
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2024

                Neurology
                covid-19,sars-cov-2,vaccination,multiple sclerosis
                Neurology
                covid-19, sars-cov-2, vaccination, multiple sclerosis

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