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Objective: To review cases of optic neuritis after COVID-19 vaccination and add similar cases to the literature., Methods: Thorough PubMed and Scopus searches were conducted, and data from studies describing optic neuritis after COVID-19 vaccination were extracted, tabulated, pooled, and reviewed., Results: We present 6 cases of optic neuritis following COVID-19 vaccination. Our literature search yielded 48 similar cases. All 54 cases were divided into 3 groups with respect to their serostatus: (1) double-seronegative or unknown serostatus optic neuritis cases, (2) myelin oligodendrocyte glycoprotein (MOG)-associated optic neuritis cases, and (3) aquaporin-4-associated optic neuritis cases. Data from each group were separately pooled and reviewed. While the most frequent vaccine among the anti-AQP4+ subgroup was BNT162b2 (Pfizer-BioNTech) (2/3), recombinant vaccines, e.g., AZD122 and Ad26.Cov2.s were mostly injected in the other subgroups (23/51). No significant gender inclination was seen among different subgroups. The mean interval from vaccination to symptom onset was less than one month in all subgroups; symptom manifestations mainly occurred after the first dose (28/54). Almost all cases showed improvement after steroid therapy±plasma exchange (52/54)., Conclusion: Despite having rare side effects such as optic neuritis, vaccination remains our most helpful protection against SARS-CoV-2. Nevertheless, larger studies are needed to ascertain the pathophysiology of such adverse effects. Likewise, the association between COVID-19 vaccination and optic neuritis warrants further investigation., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset., Methods: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018-March 10 2020) and post-pandemic onset (March 11 2020-11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use., Results: Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39-2.13; switching: OR 1.66, 95% CI 1.40-1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09-1.87; switching: OR 1.67, 95% CI 1.41-1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06-1.49; Switching: OR 1.15, 95% CI 1.02-1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41-0.73; switching: OR 0.49, 95% CI 0.41-0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41-0.57; switching: OR 0.78, 95% CI 0.62-0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15-0.48; switching: OR 0.27, 95% CI 0.17-0.44)]., Conclusions: Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges., (© 2024. The Author(s).)

Purpose: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson's Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients., Methods: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals., Results: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status., Conclusion: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Background: People with multiple sclerosis (pwMS) on anti-CD20 therapies (aCD20) and fingolimod have shown inadequate humoral responses to COVID-19 vaccines., Objective: The objective of the study was to pilot larger studies by demonstrating the safety and comparing the immunogenicity of different types of third doses in seronegative pwMS after two doses of BBIBP-CorV inactivated vaccine., Methods: In December 2021, subject to receiving their third dose, being COVID-19-naiive, and receiving no corticosteroid within two months, we measured the level of anti-SARS-CoV-2-Spike IgG in pwMS seronegative after two shots of BBIBP-CorV inactivated vaccine., Results: We included 20/29 pwMS who received adenoviral vector (AV), 7/29 who received inactivated, and 2/29 who received conjugated third doses. No serious adverse events were reported two weeks post-third dose. The pwMS receiving AV third doses showed significantly increased IgG concentrations, while only the ones not on aCD20 and fingolimod responded to inactivated third doses. An ordinal logistic multivariable generalized linear model indicated that age (per year β: -0.10, P = 0.04), type of disease-modifying therapy (aCD20 β: -8.36, P <0.01; fingolimod β: -8.63, P = 0.01; others: reference), and type of third dose (AV or conjugated β: 2.36, P = 0.02; inactivated: reference) are predictive of third dose immunogenicity among pwMS who remain seronegative after two shots of BBIBP-CorV vaccine. Statistical significance was not achieved for variables sex, MS duration, EDSS, duration of DMT, duration of third dose to IgG test, and duration from last aCD20 infusion to third dose., Conclusion: This preliminary pilot study highlights the need for further research to determine the optimal COVID-19 third dose vaccination strategy for pwMS living in areas where BBIBP-CorV vaccine has been used., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sedaghat, Etemadifar, Lotfi, Sayahi, Chitsaz, Salari and Ghasemi Movaghar.)

Background: Immunogenicity data shows blunted responses to COVID-19 vaccination among people with MS (pwMS) on certain disease-modifying therapies (DMTs). Still, it is uncertain how this data translates into the clinic., Objective: To assess the effect of DMTs and other factors on the effectiveness of inactivated vaccination in pwMS., Methods: This cohort study was conducted in a period in which Iran experienced two COVID-19 peaks caused by the Delta variant. We used multivariable cox regression to compare COVID-19-free survivals, and an ordinal logistic model to compare COVID-19 severity between vaccinated pwMS on different DMTs., Results: A total of 617 pwMS were included in the final analysis, with a mean [SD] follow-up of 25.59 weeks [5.48] after their second dose. Laboratory/imaging-confirmed breakthrough COVID-19 occurred in 15/277 (5.41%) of injectable-treated (reference), 10/61 (16.39%) of fingolimod-treated (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 2.80 [1.24, 6.29]; P = 0.01), 9/128 (7.03%) of other oral-treated (aHR [95%CI]: 1.16 [0.50, 2.68]; P = 0.73), 19/145 (13.10%) of anti-CD20-treated (aHR [95%CI]: 2.11 [1.05, 4.22]; P = 0.04), and 6/56 (10.71%) of non-treated pwMS (aHR [95%CI]: 1.52 [0.57, 4.04]; P = 0.40). Age (adjusted Odds Ratio [aOR] [95%CI]: 1.05 [1.00, 1.10], P = 0.05) number of comorbidities (aOR [95%CI]: 2.05 [1.06, 3.96], P = 0.03), fingolimod therapy (aOR [95%CI]: 10.39 [2.47, 43.62], P < 0.01), and anti-CD20 therapy (aOR [95%CI]: 4.44 [1.49, 13.23], P < 0.01) were independently associated with a more severe COVID-19 course., Conclusion: The observed results stress the importance of developing personalized vaccination schedules and reservation of COVID-19 treatment resources for older pwMS with comorbidities receiving fingolimod or anti-CD20 therapies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a relatively unknown autoimmune entity. Scant reports of post-infection/vaccination anti-NMDAR encephalitis exist. We, hereby, reviewed the relevant cases and added to the literature a possible case of anti-NMDAR encephalitis following COVID-19 vaccination with BBIBP-CorV (Sinopharm). A 50-year-old Persian woman with previously known rituximab-treated MS presented complaining of worsening neurological symptoms all gradually starting and worsening after receiving the second dose of BBVIP-CorV 2 weeks before. Notable findings in her physical examination included ataxic gait and Babinski sign. Considering an acute MS relapse, corticosteroid pulse therapy was initiated, and she was referred for MRI, which revealed multiple new plaques. Her serum sample interestingly tested positive for anti-NMDAR antibodies. CSF analysis was unfortunately not performed. She responded well to the corticosteroid pulse therapy and showed substantial resolution of the symptoms. Considering its relatively low cost of workup and the benefits of correct early diagnosis, clinicians are advised to consider autoimmune encephalitis encountering patients with progressive neurological symptoms after the administration of vaccines, including the ones for COVID-19 which are currently being used extensively.

To affirm the short-term safety of the BBIBP-CorV (Sinopharm) COVID-19 vaccine among people with multiple sclerosis (pwMS), 517 vaccinated and 174 unvaccinated pwMS were interviewed. 16.2% of the vaccinated pwMS reported at least one neurological symptom in their respective vaccine-related at-risk periods (ARP) - a period from the first dose until two weeks after the second dose of the vaccine. In a multivariable logistic regression model, the presence of comorbidities ( P  = 0.01), use of natalizumab ( P  = 0.03), and experiencing post-vaccination myalgia ( P  < 0.01) predicted the development of post-vaccination neurological symptoms. One MS relapse, one COVID-19 contraction, and one ulcerative colitis flare after the first dose, and four MS relapses after the second dose of the vaccine were the only reported serious adverse events during the ARPs. To show if the vaccine provoked MS relapses, we compared the relapse rate of vaccinated pwMS in the vaccine-related ARP with the annualized relapse rate of unvaccinated pwMS in the prior year-a measure of baseline MS relapsing activity in the respective time-using a multivariable Poisson regression model accounting for possible confounders, which failed to show any statistically significant increase ( P  = 0.78). Hence, subject to replication-as the vaccinated and unvaccinated pwMS differed in baseline characteristics-the BBIBP-CorV vaccine does not seem to affect short-term MS activity. Furthermore, as 83.33% of the unvaccinated pwMS reported fear of possible adverse events to be the reason of their vaccination hesitancy, provision of evidence-based consultations to pwMS is encouraged. Limitations of our study briefly included lack of data for self-controlled analysis of relapse rates, possible presence of recall bias, and lack of on-site validations regarding the clinical outcomes due to the remote nature.

Studies among people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have provided adequate evidence for an appraisal of COVID-19 vaccination policies among them. To synthesise the available evidence addressing the effect of MS DMTs on COVID-19 vaccines' immunogenicity and effectiveness, following the Cochrane guidelines, we systematically reviewed all observational studies available in MEDLINE, Scopus, Web of Science, MedRxiv and Google Scholar from January 2021 to January 2022 and extracted their relevant data. Immunogenicity data were then synthesised in a quantitative, and other data in a qualitative manner. Evidence from 28 studies suggests extensively lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM) treated and anti-CD20 (aCD20) treated, and lower T-cell responses in interferon-treated, S1PRM-treated and cladribine-treated pwMS-although most T cell evidence currently comprises of low or very low certainty. With every 10-week increase in aCD20-to-vaccine period, a 1.94-fold (95% CI 1.57 to 2.41, p<0.00001) increase in the odds of seroconversion was observed. Furthermore, the evidence points out that B-cell-depleting therapies may accelerate postvaccination humoral waning, and boosters' immunogenicity is predictable with the same factors affecting the initial vaccination cycle. Four real-world studies further indicate that the comparative incidence/severity of breakthrough COVID-19 has been higher among the pwMS treated with S1PRM and aCD20-unlike the ones treated with other DMTs. S1PRM and aCD20 therapies were the only DMTs reducing the real-world effectiveness of COVID-19 vaccination among pwMS. Hence, it could be concluded that optimisation of humoral immunogenicity and ensuring its durability are the necessities of an effective COVID-19 vaccination policy among pwMS who receive DMTs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Some current evidence is pointing towards an association between COVID-19 and worsening of multiple sclerosis (MS), stressing the importance of preventing COVID-19 among people with MS (pwMS). However, population-based evidence regarding the long-term post-COVID-19 course of relapsing-remitting multiple sclerosis (RRMS) was limited when this study was initiated., Objective: To detect possible changes in MS clinical disease activity after COVID-19., Methods: We conducted an observational study from July 2020 until July 2021 in the Isfahan MS clinic, comparing the trends of probable disability progression (PDP) - defined as a three-month sustained increase in expanded disability status scale (EDSS) score - and relapses before and after probable/definitive COVID-19 diagnosis in a cohort of people with RRMS (pwRRMS)., Results: Ninety pwRRMS were identified with definitive COVID-19, 53 of which were included in the final analysis. The PDP rate was significantly (0.06 vs 0.19, P = 0.04), and the relapse rate was insignificantly (0.21 vs 0.30, P = 0.30) lower post-COVID-19, compared to the pre-COVID-19 period. The results were maintained after offsetting by follow-up period in the matched binary logistic model. Survival analysis did not indicate significant difference in PDP-free (Hazard Ratio [HR] [95% CI]: 0.46 [0.12, 1.73], P = 0.25) and relapse-free (HR [95% CI]: 0.69 [0.31, 1.53], P = 0.36) survivals between the pre- and post-COVID-19 periods. Sensitivity analysis resulted similar measurements, although statistical significance was not achieved., Conclusion: While subject to replication in future research settings, our results did not confirm any increase in the long-term clinical disease activity measures after COVID-19 contraction among pwRRMS., (© 2022. The Author(s).)

Objectives: To gather, synthesize, and meta-analyze data regarding the risk factors associated with a severe course of COVID-19 among patients with multiple sclerosis (pwMS)., Methods: MEDLINE, Embase, Scopus, and WoS were searched in May 2021. Briefly, the eligibility criteria included: 1) studies assessing COVID-19 severity among adult pwMS; 2) definitive diagnoses or high clinical suspicion of COVID-19; 3) a categorization of COVID-19 severity into at least two categories; 4) quantitative effect size and precision measurements; and 5) English language; and 6) clear effect size/precision measures. internal validity of studies was assessed using the NIH Quality Assessment Tools. A list of possible risk factors was created based on the search results and was later used in extraction, synthesis, and meta-analysis of the data., Results: Thirteen studies were included in the syntheses. Outcome measures were either extracted from the papers, obtained from the primary researchers or calculated manually. The meta-analyses showed a significantly (P<0.05) increased odds of a severe COVID-19 in pwMS with all of the assessed risk factors, except smoking and most DMTs., Conclusion: This study facilitates evidence-based risk/benefit assessments in practice. Older men with progressive MS on anti-CD20 therapies are more at risk of an unfortunate COVID-19 outcome., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Various studies indicated blunted humoral responses to COVID-19 mRNA and viral vector vaccines among people with multiple sclerosis (pwMS) on sphingosine 1-phosphate receptor (S1PR) modulators and anti-CD20 therapies (aCD20); however, limited evidence was found regarding SARS-CoV-2 serology after inactivated virus vaccination., Objective: To provide evidence regarding humoral response to COVID-19 inactivated virus vaccination among pwMS on disease-modifying therapies (DMTs)., Methods: A cohort study was carried out in Isfahan, Iran, enrolling DMT-exposed pwMS and unexposed (UX) healthy participants. Post-vaccination anti-SARS-CoV-2 Spike IgG serology testing was carried out among the participants and compared between participants based on their DMT exposure, using proper statistical tests. A multivariable logistic regression model was used to control for confounding. Association between the second vaccine dose-to-phlebotomy (vac2phleb) and the humoral response was investigated in each DMT-exposed cohort, using linear regression. Among the aCD20 cohort, the association of the last aCD20 infusion-to-first vaccine dose period with serostatus was investigated using an unpaired t-test., Results: After enrolling 358 participants (144 pwMS and 214 healthy), blunted humoral responses were only observed in fingolimod (Log 10 mean diff. [SE]: 0.72 [0.18], P = 0.001) and aCD20 (Log 10 mean diff. [SE]: 0.75 [0.15], P < 0.001) cohorts compared to the UX cohort. Multivariable analysis confirmed the results. The study did not achieve enough statistical power to detect a significant association between the vac2phleb period and humoral responses. The last aCD20 infusion to first vaccination dose period was longer in the seroconverted pwMS on aCD20 (mean diff. [SE]: 8.43 weeks [2.57], P = 0.005)., Conclusion: The results of this study mirrored the results of previous studies among mRNA- or viral vector-vaccinated pwMS on DMTs. Therefore, it can be concluded that mode of action contributes less than timing, to the efficiency of vaccination strategies among pwMS on DMTs - especially the ones on S1PR modulators and aCD20. Meanwhile, the mentioned pwMS should be advised to receive early boosters and remain vigilant until further data becomes available and more efficient vaccination strategies are crafted., (Copyright © 2021. Published by Elsevier B.V.)

With the progress of COVID-19 vaccination programs worldwide, some new adverse events associated with the available vaccines may unfold, especially in subpopulations, representatives of whom were not included in phase I, II, and III clinical trials of these vaccines, such as patients with autoimmune diseases, including multiple sclerosis (MS). A 34-year-old woman presented with severe right hemiplegia and ataxia. She was diagnosed with relapsing-remitting MS (RRMS) 13 years ago and treated with rituximab (an anti-CD20 monoclonal antibody) during the last 15 months. She had received her first dose of adenovirus-vectored COVID-19 vaccine Gam-COVID-Vac (Sputnik V) three months after her last infusion of rituximab and three days before experiencing her latest MS relapse episode, preceded by mild symptoms (fatigue, myalgia, generalized weakness, etc.). Magnetic resonance imaging revealed several new periventricular, juxtacortical, brainstem, and cerebellar peduncle lesions. She received corticosteroid therapy for five consecutive days, and her neurological deficits slightly improved. Twenty-one days after receiving the first dose of the vaccine, her anti-SARS-CoV-2 antibodies were below the lower detection limit. However, a decision was made to adhere to the vaccination schedule and not risk the patient's safety against an unfortunate COVID-19 contraction, and thus, she was advised to receive the second Gam-COVID-Vac dose after discontinuation of oral steroid taper. The safety of adenovirus-based vaccines in patients with autoimmune diseases requires further investigation. Meanwhile, clinicians should raise awareness among their patients regarding the potentially limited efficacy of COVID-19 vaccination in those treated with anti-CD20 treatments. After careful, individualized risk-benefit assessments, planning a delay/pause in such treatments to create a time window for patients to receive the vaccine and develop anti-SARS-CoV-2 immunity may be recommended.

Background: COVID-19 is speculated to increase the likelihood of relapsing-remitting multiple sclerosis (RRMS) exacerbation., Objective: To investigate the association between contraction of COVID-19 and incidence of acute MS attacks in RRMS patients six months post-infection., Methods: This retrospective cohort study compares the risk of relapse in RRMS patients with (n=56) and without COVID-19 (n=69). Incidence of relapse was recorded for six-month following contraction of COVID-19. Incidence of RRMS exacerbation in patients with COVID-19 was compared to patients without COVID-19 (the independent control group) and the same patients six months prior to the COVID-19 pandemic., Results: A lower incidence rate of RRMS exacerbation was observed in patients that contracted COVID-19 than in patients who did not contract COVID-19 (incidence rate ratio: 0.275; p=0.026). Self-controlled analysis showed no significant difference in relapse rates before the COVID-19 pandemic and after contracting COVID-19 (p=0.222). The relapse risk was not different between patients who had been hospitalized due to COVID-19 severity and those who had not (p=0.710)., Conclusion: COVID-19 contraction may not increase the risk of acute MS attacks shortly following contraction. We hypothesize that COVID-19-associated lymphopenia may partly preclude the autoreactive memory cells from expansion and initiating relapses through a so-called bystander effect of COVID-19 infection., Competing Interests: Conflict of interest The authors have no conflict of interest to disclose., (Copyright © 2021. Published by Elsevier B.V.)