key: cord-0841801-g00vc5dp authors: Dinoto, Alessandro; Gastaldi, Matteo; Iorio, Raffaele; Marini, Sofia; Damato, Valentina; Farina, Antonio; Zoccarato, Marco; Sechi, Elia; Pinna, Francesca; Maniscalco, Giorgia Teresa; Barnabei, Ruggero; Zuliani, Luigi; Ferrari, Sergio; Mariotto, Sara title: Safety profile of SARS-CoV-2 vaccination in patients with antibody-mediated CNS disorders date: 2022-04-25 journal: Mult Scler Relat Disord DOI: 10.1016/j.msard.2022.103827 sha: b3be48cd37404a145b1b06a26417ca51c6b43e64 doc_id: 841801 cord_uid: g00vc5dp Objectives: In this retrospective multicenter study, we evaluated the safety of SARS-CoV-2 vaccination in patients harboring autoantibodies targeting neuronal surface and/or synaptic antigens. Methods: From eight Italian Neurology Units, we included patients with: a) serum and/or CSF positivity for specific neuronal autoantibodies; b) a compatible neurological syndrome; and c) available follow-up ≥6 weeks after vaccination with any of the approved SARS-CoV-2 vaccines. Demographics, clinical data, and information regarding previous SARS-CoV-2 infection and vaccination were collected. Disease relapses were considered “post-infectious” or “post-vaccination” when occurring within 6 weeks from infection/vaccination. Results: We included 66 patients; 7/66 (11%) had a previous history of SARS-CoV-2 infection and 2/7 (29%) had post-infection relapses. BNT162b2-Pfizer-BioNTec was administered in 55 cases (83.3%) and mRNA-1273-Moderna in 11 (16.7%). The median number of doses administered per patient was 2 (1-3) and >50% of patients did not experience side effects. Five patients (8%) had post-vaccination relapses (seizure 3/5); 4/5 improved after immunotherapy, while one did not receive immunotherapy and worsened. Patients with post-vaccination relapses had higher disability scores at vaccination (p=0.025), a trend favoring Leucine-rich glioma-inactivated protein 1 (LG1)/ glutamic acid decarboxylase 65 (GAD65) antibodies (p=0.057) and shorter time from last relapse (p=0.057). Discussion: Our data support the safety of SARS-CoV-2 vaccines in patients with neurological disorders associated with antibodies to neuronal and synaptic antigens. A total of 66 patients were included. Demographic and clinical data are summarized in Figure 1 and Table 1 . Seven (10.6%) patients had a previous history of SARS-CoV-2 infection, and 4 of them (57.1%) experienced mild flu-like symptoms while the remaining 3 were asymptomatic. One patient with glutamic acid decarboxylase 65 (GAD65) antibodies worsened (with psychiatric disturbances, tremor and seizures) 31 days after the infection without improvement after treatment with benzodiazepines and levetiracetam. Regarding vaccination, the median number of doses administered was 2 (1-3); 55 (83.3%) patients received BNT162b2-Pfizer-BioNTech, whilst 11 (16.7%) mRNA-1273-Moderna. Around half of the patients did not experience side effects (53% and 63.8% after the first and second dose, respectively). Among the side effects, pain at injection site was the most frequently reported (24.2% and 15.5% after the first and second dose, respectively). When comparing patients with and without post-vaccination relapses, relapsing cases had higher CASE scores at vaccination (p=0.021) and a trend favoring Leucine-rich glioma-inactivated protein 1 (LG1)/GAD65 antibodies positivity (p=0. 054) and a shorter time from last relapse (p=0.057), Supplementary Table 3 . Our multicenter retrospective study shows that SARS-CoV-2 vaccination is safe in patients with neurological disorders associated with antibodies to neuronal and synaptic antigens since 1. vaccine-related side effects occur in about half of patients but are typically mild and showed a rate comparable with other autoimmune neurological conditions [2, 8] ; 2. post-vaccination relapses rarely occur in these conditions (7.6%); 3. postvaccination relapses generally show a favorable outcome to immunotherapy. Of note, additional factors have to be considered as possible contributors to the few relapses herein observed after vaccination. In this context, seizures were a common manifestation in post-vaccination relapses and always occurred in patients with a known history of epilepsy. Since an increase in seizure frequency after vaccination has also been reported in a minority of patients with non-autoimmune epilepsy, the possibility that systemic/structural rather than autoimmune factors might be the leading cause of this post-vaccine symptom should be considered [6, 7] . The association between pre-vaccination disease severity, which represents a risk factor for remote symptomatic seizures, and the occurrence of post-vaccination worsening further reinforces this hypothesis. Similarly, the worsening of ataxia and movement disorder associated with psychiatric disturbances after vaccination may be related to the progressive course of the underlying condition (in one patient with ataxia with metabotropic glutamate receptor 1 (mGLUR1) antibodies, and in one patient with ataxia and progressive encephalomyelitis with rigidity and myoclonus with GAD65 antibodies, respectively). In accordance, the incidence of relapses did not increase after vaccination in other neurological autoimmune disorders, even though transient worsening of neurological symptoms may occur without evidence of disease activity [8, 9] . Although most of our patients showed a favorable response after treatment with immunotherapy, which might suggest an autoimmune nature of the event, the lack of further confirmatory investigations (such as brain magnetic resonance imaging scans or CSF analysis) prevent a definitive discrimination between the occurrence of a transient worsening and a definite immune-mediated relapse. Our study is limited by the small sample size, the retrospective design, the predominant administration of mRNA-based vaccination, and the lack of evaluation of CNS antibody titers before and after vaccination. Despite these limits, our data supports the safety of SARS-CoV-2 vaccination in patients with antibody-mediated disorders and may help clinicians to properly inform patients with these rare conditions about the overwhelming benefits of vaccination. Funding source: this research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors report no competing interests in relation to this study. 2021) mRNA COVID-19 vaccines do not increase the shortterm risk of clinical relapses in multiple sclerosis Risk of disease relapse following COVID-19 vaccination in patients with AQP4-IgG-positive NMOSD and MOGAD. Mult Scler Relat Disord 103424 Neurological autoimmune diseases following vaccinations against SARS-CoV-2: a case series Postvaccinal Encephalitis after ChAdOx1 nCov-19 Potential autoimmune encephalitis following yellow fever vaccination: A report of three cases Acute symptomatic seizures secondary to autoimmune encephalitis and autoimmune-associated epilepsy: Conceptual definitions COVID-19 vaccine take-up rate and safety in adults with epilepsy: Data from a multicenter study in China Patient-reported safety and tolerability of the COVID-19 vaccines in persons with rare neuroimmunological diseases Safety of the BNT162b2 COVID-19 vaccine in multiple sclerosis (MS): Early experience from a tertiary MS center in Israel Figure legends Figure 1: (a) antibody positivity and (b) clinical phenotype of included patients. Double positive patients harbored the following antibodies: CASPR2+LGI1 n= 2; GABAbR+GAD65 n=1 Those with multifocal involvement had: autoimmune encephalitis and myasthenia gravis n=1; stiff person syndrome and cerebellar ataxia n=1; overlapping features between IgLON5 and GAD65 (double positive patient) n=1; limbic encephalitis and chorea n=1; cerebellar ataxia and progressive encephalomyelitis with rigidity and myoclonus n=1 CASPR2: contactin-associated protein-like 2, GABAaR: gammaaminobutyric acid A receptor, GABAbR: gamma-aminobutyric acid B receptor, GAD65: glutamic acid decarboxylase 65, GlyR: glycine receptor, LGI1: leucine-rich glioma-inactivated protein 1, mGLUR: metabotropic glutamate receptor 1, AChR: acetylcholine receptor Availability of data and material: Data are available upon reasonable request.Ethics approval: approval was obtained from the ethics committee of University Verona (56COVIDCESC). Consent to publish: informed consent was acquired.