key: cord-0902946-m0t35kt5 authors: Lotan, Itay; Wilf‐Yarkoni, Adi; Friedman, Yitzhak; Stiebel‐Kalish, Hadas; Steiner, Israel; Hellmann, Mark A. title: Safety of the BNT162b2 COVID‐19 vaccine in multiple sclerosis (MS): Early experience from a tertiary MS center in Israel date: 2021-08-02 journal: Eur J Neurol DOI: 10.1111/ene.15028 sha: 61d07c9b92c5c196fa50d2dd328df83fdf66b796 doc_id: 902946 cord_uid: m0t35kt5 BACKGROUND AND PURPOSE: Although the COVID‐19 vaccines are currently recommended for people with multiple sclerosis (MS), the fact that they were not specifically tested in people with MS raises uncertainty regarding their safety in this population. The purpose of this study was to report real‐life safety data of the BNT162b2 COVID‐19 vaccine in a cohort of MS patients. METHODS: An anonymous survey was distributed to 425 MS patients. Participants were asked general demographic and disease‐related questions and specific questions regarding the safety profile of the COVID‐19 vaccine. RESULTS: Of the 425 MS patients, 262 completed the questionnaire. The median (range) participant age was 42 (22–79) years, 199 participants were women (75.9%), and 66 participants (25.2%) had associated comorbidities. A total of 198 participants (75.6%) were treated with disease‐modifying therapies. In all, 239 participants (91.2% of the responders) had received the BNT162b2 COVID‐19 vaccine. Of these, 182 (76.1%) were aged <55 years, and 57 (23.9%) were aged >55 years. Adverse events were reported by 136 participants (56.9%; 52.5% of those aged <55 years and 40.3% of those aged >55 years; p = 0.1517) and 36 participants (15.1%) reported new or worsening neurological symptoms following the vaccination, the most frequent being sensory disturbances (21 participants, 58.3%). Most symptoms occurred within the first 24 h after vaccination and resolved within 3 days. A total of 28 participants (77.8%) did not require any medication to treat their symptoms. CONCLUSIONS: This survey indicates an overall favorable safety profile of the BNT162b2 vaccine in people with MS. These data should be confirmed in further prospective, large‐scale studies. To control the pandemic, a global effort supported by academic, industrial, and governmental sectors has been focusing on the development of effective vaccines at record speed. This effort has culminated in the recent US Food and Drug Administration (FDA) approval of three vaccines, while others are approaching the final stages of clinical trials and are expected to be approved in the near future [4, 5] . Sinopharm [4] [5] [6] [7] . The approved vaccines have been tested in large-scale phase 3 trials, which recruited both healthy individuals and people with chronic medical conditions [8] . Although the COVID- 19 vaccines have not been tested specifically in people with neurological and autoimmune diseases, many expert committees recommend their use in various neurological disorders, including multiple sclerosis (MS) [9] [10] [11] [12] . However, the lack of information regarding the safety and efficacy of the vaccines in this specific population is a cause of uncertainty for both patients and physicians. Hence, real-life data on the safety of the COVID-19 vaccine is of utmost importance. A recent study reported a higher incidence of COVID-19 in an MS cohort compared to the general population [13] . Although most studies do not indicate a more severe course of the disease among MS patients [14, 15] , some subpopulations, such as patients treated with anti-CD20 therapies, may be at higher risk for severe outcome following COVID-19 infection [16, 17] . The importance of effective measures to prevent the disease in this context is therefore understandable. The COVID-19 vaccination campaign began in Israel in December 2020 using the BNT162b2 (Pfizer) vaccine as its sole vaccine. In the clinical trial that led to its approval by the FDA, the safety profile of the vaccine, administered in two injections of 30 μg 21 days apart, was reported to be similar to that of other viral vaccines. Adverse events were more common among participants aged <55 years of age compared to those aged >55 years. The most common adverse event was pain at the injection site, reported by 83% of those aged <55 years and by 71% of those aged >55 years after the first dose, and by 78% of those aged <55 years of age and 66% of those aged >55 years after the second dose. Systemic adverse events were reported less frequently than the local reactions, were more common after the second dose, and included fatigue, headache, fever, and chills [8] . Israel is currently the leading country in the world in the percentage of its population that received both doses of the vaccine [18] . Early efficacy outcomes of the BNT162b2 vaccine in Israel confirm that real-life vaccine efficacy is as good as the data reported from Pfizer's earlier clinical trials [19] . Given the successful application of the vaccine campaign in Israel, we aimed to report our early safety experience with the BNT162b2 COVID-19 vaccine in a cohort of MS patients. This single-center study was conducted using an anonymous questionnaire that was distributed to MS patients from the Neuroimmunology Clinic at the Rabin Medical Center. In the first part of the questionnaire, participants were asked general demographic and disease-related questions, including questions on age, gender, use of disease-modifying therapies, recent treatment with corticosteroids, and associated comorbidities. The second part of the questionnaire was dedicated to the safety profile of the COVID-19 vaccine. In this part, participants were asked if they had received the vaccine (first or both doses), the date of vaccination, and questions on the presence, and type of early reactions (i.e., occurring within the first week from vaccination) to the vaccine (pain/redness/ swelling at the injection site, generalized muscle pain, headache, dizziness, fever, chills, fatigue, or other), and presence, type and timing of new or worsening neurological symptoms following the vaccination. In case of worsening neurological symptoms after the vaccination, additional information regarding the need for specific treatment and the duration of symptoms was requested. The study data were collected and managed using REDCap, an electronic data capture tool [20, 21] . Data analysis was performed between April 17, 2021 and April 22, 2021. The study was approved by the Rabin Medical Center institutional review board (study approval number 0061-21-RMC). An invitation email with a link to the survey was distributed to 425 MS patients between March 15, 2021 and April 17, 2021. Patients were informed that completion of the survey was not obligatory. As the data were anonymous, informed consent was not requested. Statistical analysis was performed using GraphPad Prism version 9.1.2 (GraphPad Software, San Diego, CA, USA). Descriptive statistics are presented as total counts and percentages, median and range. Fisher's exact test was used for comparison of nonparametric variables between groups. Due to the exploratory nature of the study, no adjustment for multiple comparisons was made. A total of 262 participants (61.6% response rate) completed the questionnaire. The median (range) age was 42 (22-79) years and 199 of the respondents were women (75.9%). Sixty-six participants (25.2%) reported associated comorbidities, including hypertension (32 participants, 12.2%), diabetes mellitus (11 participants,4.2%) lung diseases (five participants, 2.2%), heart disease (four participants, 1.5%), obesity (37 participants, 14.1%) and malignancy (four participants, 1.5%). A total of 198 participants (75.6%) were treated with disease-modifying therapies (DMTs), and 17 (6.5%) were treated with corticosteroids in the month preceding the first vaccination. Table 1 summarizes the demographic and disease-related characteristics of the study population. A total of 239 participants (91.2% of the responders) had received the vaccine. Eighteen (7.5%) had received only one dose, and 221 (92.5%) had received both doses. The reason for receiving just one dose of the vaccine was a prior diagnosis of COVID-19 in seven participants (38.9%) and personal or medical concern because of side effects after the first No association between type of DMT and frequency and type of adverse events was detected. The rate of adverse events is summarized in Table 2 . Thirty-six participants ( A massive COVID-19 vaccination strategy is currently being imple- The spectrum of adverse events reported in our study is comparable to that reported in Pfizer's phase 3 clinical trial [8] . As seen in the general population, local reactions (i.e., pain, redness, and swelling at the injection site) were the most common adverse events. Also in line with what was reported in the general population, adverse events among MS patients were more frequent in the younger age group (<55 years) compared to older individuals (>55 years). A possible explanation for this observation may be related to the more vigorous immune response mounted by younger individuals. In fact, the occurrence of adverse events following vaccination is thought to be mediated by immunological responses, reflecting the activity of the immune system [22, 23] . As the immune system tends to gradually deteriorate with age [24, 25] , older people often experience less pronounced side effects after vaccination [26, 27] . However, the overall rate of adverse events among our survey respondents is lower than that reported in the general population [8] . other (non-live-attenuated) vaccines that were not related to an increased risk of MS relapse [28, 29] . Vaccine hesitancy refers to a broad range of factors causing low vaccination uptake. Among these factors, confidence in the safety and effectiveness of the vaccine plays an important role [30] . Vaccine hesitancy regarding the pneumococcal vaccine and, more recently, the COVID-19 vaccines has been reported in a significant proportion of MS patients [31] [32] [33] . The data reported in the present study, which are in line with another early safety report on the BNT162b2 vaccine in MS [34] , may help to address the safety concerns related to the vaccine in this population. The limitations of this study are mostly related to the relatively small number of responders. Also, the nonresponding rate of approximately 40% may bias the results, as the rate of adverse events and new or worsening neurological symptoms among those who did not respond may be different than that reported by the responders. In conclusion, the safety profile of the BNT162b2 vaccine in peo- specific treatment, and resolve within a few days. These data should be further validated in additional prospective, large-scale studies. The authors declare that there is no conflict of interest. The authors do not have any specific agreements with the vaccine manufacturer for data delivery or similar. 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