CoVacU18-Study: Long-Term Safety of BNT162b2 in Children under 18 Years in Germany

CoVacU18-Study: Long-Term Safety of BNT162b2 in Children under 18 Years in Germany | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article CoVacU18-Study: Long-Term Safety of BNT162b2 in Children under 18 Years in Germany Vivien Grieshaber, Christoph Strumann, Sarah Holzwarth, Nicole Toepfner, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4566186/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Retrospective evaluation of long-term safety of BNT162b2 in children < 18 years in Germany compared to non-SARS-CoV-2 vaccines. Methods This investigator initiated longitudinal cohort study retrospectively assessed the long-term safety of BNT162b2 using an online questionnaire addressed to parents of vaccinated children. Between May 25th and July 11th we contacted 15423 E-Mail-addresses registered in databases of vaccination centre. Inclusion criteria were at least one BNT162b2 vaccination after October 1st, 2021 < 18 years of age and using a valid authentication code. An active comparator analysis was performed to compare BNT162b2 to non-SARS-CoV-2 vaccines. Results 3228 children (median age, 5.7 [IQR, 3.4–9.5]; male, 49.6%) who received ≥ 1 dose of BNT162b2 < 18 years were followed up for a median of 524 days (IQR, 500–553 days). Across all age groups, the active-comparator analysis revealed significantly increased rates of post-vaccination symptoms in 10 of 11 categories occurring after BNT162b2 compared to non-SARS-CoV-2 vaccines. In 41 cases symptom duration ≥ 90 days are reported and most frequently affected the neurological, psychological and dermatological system. Relative probability of reporting a serious adverse event was significantly increased if participants were female (OR, 4.55; 95% CI, 2.10–9.88) or took long-term medication (OR, 3.67; 95% CI, 1.39–9.69). No causality can be verified based on the available data. Conclusion BNT162b2 is well tolerated by 98% of children, but specific symptoms occur significantly more frequently than in non-SARS-CoV-2 vaccines. In rare cases (1.4%) symptoms persisted ≥ 90 days. Question of causality should further be scrutinized in future prospective studies. Clinical Trial Registration : This study was registered at the German Clinical Trials Register (Register-ID: DRKS00031994). mRNA vaccine BNT162b2 Safety Children Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction The mRNA-based COVID-19 vaccine BNT612b2 was approved with a delay for children < 12 years due to a lack of data on tolerability in this age group. Since October 2022 children from the age of 6 months could also be vaccinated on-label in Germany. The circumstances of off-label vaccinations in children in Germany have been described in the previous CoVacU5-study ( 1 ). Until the day of April 8, 2023, 22.4% of 5-11-year-olds and only 0.1% of under 4-years-old children received ≥ 1 COVID-19 vaccination in Germany. In contrast, 69.9% of 12-17-year-olds received basic immunization ( 2 ). As of January 2024 the BNT162b2-administration is recommended by the Standing Commission on Vaccination (STIKO) to be given as a three-dose series in children aged six months to four years (3µg/dose) and in a two-dose series in children aged 5–11 years (10 µg/dose) as well as in adolescents (30µg/dose) ( 3 ). Due to the mostly mild course of SARS-CoV-2 infections in children, the recommendations refer to children with underlying diseases that are associated with an increased risk of severe disease progression and complications ( 4 – 7 ). Risk factors for a severe course of COVID-19 in childhood have been identified in several studies and included prematurity, presence of coinfections and comorbidities ( 4 , 5 ). The decision for or against the COVID-19 vaccination remains a present and relevant issue, especially for parents whose children are meeting risk factors or are in regular contact with people at risk. The mRNA-based COVID-19 vaccine BNT162b2 has proven to be well tolerated in children ≥ 6 months but safety signals have emerged due to an increased incidence of myocarditis and pericarditis following vaccination ( 1 , 8 – 10 ). The risk of suffering SARS-CoV-2 infection or visiting a healthcare facility due to the infection has been demonstrably reduced by the vaccination ( 11 , 12 ). Despite the good prognosis for healthy children who suffer SARS-CoV-2 infection, the assessment of long-term tolerability of the mRNA-based COVID-19 vaccine remains of great importance, but to our knowledge, there have been no studies to date. The previous CoVacU5 study already registered significant differences between the occurrence of certain symptom categories compared to non-SARS-CoV-2 vaccinations in < 5-year-olds ( 1 ). We conducted the present study to further elucidate long-term tolerability after (repeated) BNT162b2 administration, filling a current knowledge gap. The ensuing information may contribute to characterize the long-term safety and risk profile of mRNA based BNT162b2 vaccine and to detect rare complications that may have escaped previous reports from smaller datasets or less systematic follow-ups. Methods Study Design This study was designed as a retrospective longitudinal cohort study. We evaluated the safety and tolerability of BNT162b2 mRNA-based COVID-19 vaccine (Comirnaty, Comirnaty Original/Omicron BA.1 or BA.4–5) in children vaccinated in Germany < 18 years of age. All vaccinations considered were administered on a voluntary basis before the study was planned. The central requirement for vaccination was that parents or legal representatives provided written individual informed consent to the vaccination and were informed by the attending physicians about potential adverse effects and in case of need about the liability of off-label medicine use under German law. The attending physicians were obliged by the Infection Protection Act to report any vaccination reaction exceeding the usual level/any severe adverse effects experienced by the children to the responsible public health department, regardless of the current study. The present study was based on an online questionnaire addressed to the parents/legal representatives of vaccinated children. Eligible participants were identified from electronic databases of ten cooperating outpatient medical practices and the nationwide layperson-initiated SARS-CoV-2 vaccination social media program BildungAberSicher in Germany. During the study period of May 25th to July 11th, 2023 legal guardians were contacted three times via email-addresses registered in the database to complete the online-survey. Participation was only possible using an individual authentication code. The study database was closed on July 11th, 2023 and data were extracted for analysis in a pseudonymous mode. Exclusion criteria were duplicate records regarding to the variables “age”, “sex”, “weight”, “height” and the authentication code without indication that children were twins/triplets. Datasets without valid authentication code as proof of invitation, and SARS-CoV-2 vaccinations with exclusively other than BNT162b2 (Comirnaty, Comirnaty Original/Omicron BA.1 or BA.4–5) were excluded. Serious Adverse Events (SAE) were defined as any event resulted in hospitalization or death due to the symptoms described and a symptom duration ≥ 90 days. The approval of this study project was given by the Ethical Committee of the University of Witten/Herdecke e. V. (Application number S-61/2023). Written informed consent to participate in this study and for subsequent data processing was provided by the legal guardians of the children. This study follows STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) reporting guidelines. Study Procedure All study data were collected using REDCap (Research Electronic Data Capture). Data were stored at the Koordinierungszentrum für Klinische Studien Dresden (KKS) at the University Medical Center Dresden, TU Dresden, Germany. The online survey was designed to be completed within 30 minutes retrospectively to report on vaccination reactions and was pretested in 10 pilot test runs. Demographic data were collected including age, gender, weight, height, number of COVID-19 vaccinations received, comorbidities, and concurrent medications. Vaccination reactions were queried in eleven symptom categories by close-ended questions and free-test responses. The symptom categories were the following: injection-site symptoms; general reactions; fever; any symptoms of the musculoskeletal, cardiovascular, pulmonary, otolaryngological, gastrointestinal, neurological, psychological or dermatological system including lymph node reactions. Radio-button choice was used to record individual symptoms, which were characterized in terms of initial onset after vaccination, duration and any required measures using close-ended questions. A self-assessment of the medical threat was recorded on a scale of 0–10 (0 = not threatening, 10 = very threatening). Free-text responses were available in all categories if individual vaccination reactions were not represented in multiple-choice response options. To perform an active comparator analysis, the tolerability of common non-SARS-CoV-2 vaccines, administered in the same children within three months before or after BNT162b2 administration, was surveyed for all symptom categories. Free-text responses were queried for the German terms for myocarditis/pericarditis. Outcomes The primary outcome was the frequency of self-reported categorized symptoms after BTN162b2 administration (Comirnaty, Comirnaty Original/Omicron BA.1 or BA.4–5) stratified by age group (0–23 months, 2–4 years, 5–11 years, 12–17 years) compared to common non-SARS-CoV-2 vaccines. The secondary outcomes were onset, duration and self-assessed medical threat of symptoms occurring after BNT162b2 administration as well as measures taken. Furthermore, the frequencies of vaccination reactions compared between mono- and bivalent BNT162b2 vaccines were of interest. Statistical Analysis All statistical analyses were performed using IBM SPSS Statistics, version 29.0.0.0 (241). Statistical significance was set at P < 0.05. Odds ratio (OR) were calculated using the Wald method and from logistic regression models adjusted for age group (0–23 months, 2–4 years, 5–11 years, 12–17 years), sex, weight, height and comorbidities. Logistic regression models were performed with any symptom or the eleven individual categories of post-vaccination symptoms as dependent variables and BNT162b2 vs. non-SARS-CoV-2 vaccines as variable of interest. Duration and impact of the symptoms were assessed in additional logistic models. Calculated p-values and 95% CI were adjusted using the Bonferroni method. Results Study Population For participant recruitment 15622 invitations were sent to eligible individuals, 3841 responses were received, corresponding to a response rate of 24.6%. The flowchart in Fig. 1 shows the total number of exclusions and reasons for exclusion. A total of 3228 children who received at least one dose of BNT162b2 were included in this study (median age, 5.7 years [IQR, 3.4–9.5]) and observed over a median period of 524 days (IQR, 500–553 days). Basic immunization (≥ 2 BNT162b2 doses) was administered in 3119 participants (96.6%). Overall, 49.6% were male, 12.3% had an underlying chronic disease and 7.6% were taking permanent medication. Most often reported pre-existing conditions were pulmonary (n = 120 [3.7%]), cardiovascular (n = 53 [1.6%]) and chromosomal aberrations (n = 37 [1.1%]) (eTable 1). Each LOT-number given was examined for authenticity and the validity regarding to the vaccination date via the drug information system of the Federal Institute for Drugs and Medical Devices in Germany ( 13 ). LOT-numbers were also used to check vaccine variant (mono- or bivalent) and to correct information provided if necessary. Overall, 9510 vaccinations were examined, and a valid LOT-number was reported for 76.6%, no LOT-number was reported for 22.1%. Table 1 Characteristics of the Cohort Related to the Chronological BNT162b2 Vaccinations One Through Six, n/N (%) Characteristics 1st BNT vaccination 2nd BNT vaccination 3rd BNT vaccination 4th BNT vaccination 5th BNT vaccination 6th BNT vaccination n 3204 3120 1898 1003 227 36 Sex Male (%) 1595 (49.8) 1555 (49.8) 963 (50.7) 522 (52.0) 113 (49.1) 19 (52.8) Female (%) 1600 (49.9) 1556 (49.9) 927 (48.8) 475 (47.4) 112 (49.3) 16 (44.4) Age, median, y 5.7 5.8 6.4 6.6 7.5 7.6 0–23 months 407 (12.7) 369 (11.8) 144 (7.6) 53 (5.3) 9 (4.0) 0(0.0) 2–4 years 1006 (31.4) 958 (30.7) 588 (31.0) 295 (29.4) 54 (23.8) 8 (21.6) 5–11 years 1407 (43.9) 1381 (44.3) 812 (42.8) 484 (48.3) 123 (54.2) 22 (59.5) 12–17 years 360 (11.2) 379 (12.1) 337 (17.8) 150 (15.0) 40 (17.6) 5 (14.3) Unknown a 24 (0.7) 33 (1.1) 17 (0.9) 21 (2.1) 1 (0.4) 1 (2.8) Proportion of bivalent vacci-nations, (BA.1 or BA.4–5) 50 (1.6) 61 (1.9) 351 (18.5) 846 (84.4) 210 (92.5) 34 (94.5) Dosage, median (min.; max.), µg 10 (1,5; 30) 10 (1,5; 30) 10 (3;30) 15 (3;30) 15 (3;30) 15 (5;30) Unknown 441 (13.8) 432 (13.8) 128 (6.7) 31 (3.1) 3 (1.3) 0 (0.0) Comorbidities 395 (12.3) 381 (12.2) 271 (14.3) 150 (15.0) 36 (15.9) 9 (25.0) Long-term medication 241 (7.5) 234 (7.5) 171 (9.0) 91 (9.1) 25 (11.0) 6 (16.7) Frequency of Reported Symptoms and Measures Taken After the First Three Wildtype-BNT162b2-Vaccinations Reported symptoms following administration of monovalent BNT162b2 (Comirnaty Original) vaccine were descriptively analyzed chronologically, divided into eleven symptom categories and stratified by age group (Fig. 2 A-D). Most common symptoms related to local-injection site, general condition, fever and musculoskeletal system. In comparison of the first to third vaccination a decreasing trend in the frequency of local-injection site reactions, fever, general and neurological symptoms after each subsequent vaccination is shown. In contrast, psychological and dermatological events increased in 12-17-year-olds. Adolescents were twice as likely to report neurological symptoms as children aged 5–11 years. Odds ratio to report ≥ 1 symptom was increased if the child was female (OR, 1.34 [95% CI, 1.14–1.57]) or had an underlying chronic disease (OR, 1.34 [95% CI, 1.05–1.72]). A maximum of 6.2% received medications such as antipyretics and a maximum of 0.5% received outpatient medical treatment after at least one of three vaccinations. No significant correlation between the frequency of reported vaccine reactions and the applied vaccine dose was found. Post-vaccination symptoms after all analyzed BNT162b2-vaccinations are shown in the Supplement (eTable 2–17). Monovalent and Bivalent BNT162b2 Vaccine in Comparison In a subgroup of 1842 children, the frequency of any reported symptom after receiving the bivalent or monovalent BNT162b2 vaccine was compared. For this purpose, reports of children who received the bivalent BNT162b2 as the 3rd or 4th chronological vaccination for the first time were compared with those who received monovalent BNT162b2 exclusively but in the same sum. The probability of any symptom reported after the bivalent BNT162b2 vaccination was slightly increased (OR, 1.2; 95% CI, 0.92–1.53 [bivalent vs. monovalent, 3rd chronological vaccination]; OR, 1.15; 95% CI, 0.72–1.69 [bivalent vs. monovalent, 4th chronological vaccination]) but not significant. The frequency of reported symptoms after mono- or bivalent BNT162b2-vaccination were stratified by age group (eTable 18). Active Comparator Analysis for BNT162b2 vs. Non-SARS-CoV-2-Vaccinations An active comparator analysis was performed in a subgroup of 1185 children who received at least both a BNT162b2 COVID-19 vaccination and a common non-SARS-CoV-2 vaccination authorized in Germany at a maximum interval of 3 months in the period from January 5th, 2021 to March 31st, 2023. The minimum observation period for both vaccines was 2 months. Overall, information of 7532 BNT162b2 vaccinations and 1764 non-SARS-CoV-2 vaccinations were considered. Results stratified by age group are shown in Table 2 A-D. The comparison was also performed across all age groups 0–17 years (eTable 19). Table 2 A: Active-Comparator Analysis of Symptoms Occurring after BNT162b2 and Non-BNT162b2 vaccinations, Age 0–23 months Variable Frequencies, No./total No. (%) Logistic regression BNT162b2 (%) Non-SARS-CoV-2 (%) OR (95% CI) P value Disposition Physical rest 58/279 20.8 75/279 26.9 0.71 (0.47–1.05) 0.09 Medication 31/279 11.1 74/279 26.5 0.34 (0.21–0.54) < 0.001 Ambulatory 3/279 1.1 2/279 0.7 1.51 (0.25–9.17) 0.65 Inpatient 0/279 0.0 1/279 0.4 N.A. Mortality 0/279 0.0 0/279 0.0 N.A. Symptoms Any symptom reported 154/279 55.2 134/279 48.0 1.30 (0.93–1.82) > 0.99 b Local 121/279 43.4 91/279 32.6 1.58 (1.11–2.25) 0.12 b General 71/279 25.5 103/279 36.9 0.57 (0.39–0.82) 0.04 b Fever 39/279 14.0 82/279 29.4 0.37 (0.24–0.58) 0.01 b Musculoskeletal 3/279 1.1 4/279 1.4 0.75 (0.16–3.38) > 0.99 b Gastrointestinal 8/279 2.9 8/279 2.9 0.85 (0.28–2.58) > 0.99 b Otolaryngological 1/279 0.4 0/279 0.0 N.A. Pulmonary 3/279 1.1 0/279 0.0 N.A. Cardiovascular 0/279 0.0 0/279 0.0 N.A. Neurological 2/279 0.7 0/279 0.0 N.A. Psychological 5/279 1.8 0/279 0.0 N.A. Dermatological 6/279 2.2 2/279 0.7 3.11 (0.61–15.73) > 0.99 b b adjusted for multiple testing by Bonferroni correction. All individuals in the Non-BNT162b2 group had also received at least one dose of BNT162b2 between January 5th ,2021 to March 31,2023 but here reported symptoms occurring after the Non-BNT162b2 are shown. Table 2 B: Active-Comparator Analysis of Symptoms Occurring after BNT162b2 and Non-BNT162b2 vaccinations, Age 2–4 years Frequencies, No./total No. (%) Logistic regression Variable BNT162b2 (%) Non-SARS-CoV-2 (%) OR (95% CI) P value Disposition Physical rest 86/346 24.9 39/346 11.3 2.58 (1.70–3.93) < 0.001 Medication 29/346 8.4 23/346 6.6 1.30 (0.73–2.33) 0.38 Ambulatory 4/346 1.2 0/346 0.0 N.A. Inpatient 0/346 0.0 0/346 0.0 N.A. Mortality 0/346 0.0 0/346 0.0 N.A. Symptoms Any symptom reported 239/346 69.1 87/346 25.1 6.69 (4.77–9.38) 0.01 b Local 217/346 62.7 76/346 22.0 6.09 (4.33–8.57) 0.01 b General 89/346 25.7 46/346 13.3 2.22 (1.48–3.32) 0.01 b Fever 38/346 11.0 33/346 9.5 1.18 (0.71–1.96) > 0.99 b Musculoskeletal system 13/346 3.8 5/346 1.4 2.70 (0.95–7.70) 0.72 b Gastrointestinal 10/346 2.9 1/346 0.3 10.49 (1.33–82.71) 0.31 b Otolaryngological 3/346 0.9 2/346 0.6 1.52 (0.25–9.28) > 0.99 b Pulmonary 2/346 0.6 0/346 0.0 N.A. Cardiovascular 1/346 0.3 0/346 0.0 N.A. Neurological 11/346 3.2 1/346 0.3 11.53 (1.48–90.17) 0.24 b Psychological 3/346 0.9 2/346 0.6 1.50 (0.25–9.08) > 0.99 b Dermatological 16/346 4.6 1/346 0.3 16.94 (2.23-128.62) 0.07 b b adjusted for multiple testing by Bonferroni correction. All individuals in the Non-BNT162b2 group had also received at least one dose of BNT162b2 between January 5th ,2021 to March 31,2023 but here reported symptoms occurring after the Non-BNT162b2 are shown. Table 2 C: Active-Comparator Analysis of Symptoms Occurring after BNT162b2 and Non-BNT162b2 vaccinations, Age 5–11 years Frequencies, No./total No. (%) Logistic regression Variable BNT162b2 (%) Non-SARS-CoV-2 (%) OR (95% CI) P value Disposition Physical rest 148/450 32.9 67/450 14.9 2.79 (1.99–3.90) < 0.001 Medication 57/450 12.7 27/450 6.0 2.24 (1.37–3.66) 0.001 Ambulatory 7/450 1.6 0/450 0.0 N.A. Inpatient 2/450 0.4 0/450 0.0 N.A. Mortality 0/450 0.0 0/450 0.0 N.A. Symptoms Any symptom reported 345/450 76.7 153/450 34.0 4.06 (2.05–8.03) 0.01 b Local 321/450 71.3 144/450 32.0 5.28 (3.94–7.06) 0.01 b General 130/450 29.0 56/450 12.4 2.89 (2.03–4.13) 0.01 b Fever 51/450 11.3 24/450 5.3 2.34 (1.39–3.97) 0.01 b Musculoskeletal system 43/450 9.6 12/450 2.7 4.06 (2.05–8.03) 0.01 b Gastrointestinal 12/450 2.7 1/450 0.2 12.58 (1.62–97.50) 0.12 b Otolaryngological 6/450 1.3 1/450 0.2 6.21 (0.74–52.31) > 0.99 b Pulmonary 4/450 0.9 1/450 0.2 4.08 (0.45–36.93) > 0.99 b Cardiovascular 8/450 1.8 1/450 0.2 7.49 (0.90-62.27) 0.72 b Neurological 43/450 9.6 3/450 0.7 14.86 (4.55–48.49) 0.01 b Psychological 8/450 1.8 0/450 0.0 N.A. Dermatological 30/450 6.7 6/450 1.3 5.23 (2.14–12.78) 0.01 b b adjusted for multiple testing by Bonferroni correction. All individuals in the Non-BNT162b2 group had also received at least one dose of BNT162b2 between January 5th ,2021 to March 31,2023 but here reported symptoms occurring after the Non-BNT162b2 are shown. Table 2 D: Active-Comparator Analysis of Symptoms Occurring after BNT162b2 and Non-BNT162b2 vaccinations, Age 12–17 years Frequencies, No./total No. (%) Logistic regression Variable BNT162b2 (%) Non-SARS-CoV-2 (%) OR (95% CI) P value Disposition Physical rest 52/110 47.3 15/110 13.6 6.06 (3.05–12.03) < 0.001 Medication 16/110 14.5 4/110 3.6 4.68 (1.49–14.66) 0.008 Ambulatory 2/110 1.8 0/110 0 N.A. Inpatient 1/110 0.9 0/110 0 N.A. Mortality 0/110 0.0 0/110 0 N.A. Symptoms Any symptom reported 94/110 85.5 38/110 34.5 12.59 (6.28–25.26) 0.01 b Local 89/110 80.9 36/110 32.7 9.59 (5.01–18.35) 0.01 b General 49/110 44.5 10/110 9.1 8.16 (3.77–17.66) 0.01 b Fever 11/110 10.0 2/110 1.8 6.14 (1.32–28.59) 0.25 b Musculoskeletal 16/110 14.7 6/110 5.5 4.16 (1.33–12.98) 0.17 b Gastrointestinal 1/110 0.9 0/110 0.0 N.A. Otolaryngological 3/110 2.8 0/110 0.0 N.A. Pulmonary 1/110 0.9 0/110 0.0 N.A. Cardiovascular 1/110 0.9 0/110 0.0 N.A. Neurological 21/110 19.1 3/110 2.7 8.42 (2.39–26.68) 0.01 b Psychological 4/110 3.6 0/110 0.0 N.A. Dermatological 9/110 8.2 0/110 0.0 N.A. b adjusted for multiple testing by Bonferroni correction. All individuals in the Non-BNT162b2 group had also received at least one dose of BNT162b2 between January 5th ,2021 to March 31,2023 but here reported symptoms occurring after the Non-BNT162b2 are shown. Serious Adverse Events Overall, 48 SAEs were reported in 45 children (1.39%). 69% of the affected children were ≥ 5 years old. A symptom duration of ≥ 90 days (median onset, 1.5 days; median duration at time of survey, 126.5 days) was reported for 41 children, in 22 of these symptoms were still persistent at the time of survey (eTable 20–21). Long-lasting symptoms involved most often the psychological, neurological and dermatological system (eTable 8–17). A total of 117 vaccine doses were administered, of which the doses were unknown in 24.7% (29 doses) and the current age-group-specific STIKO recommendations ( 14 ) were exceeded in 31.6% (37 doses). Seven hospitalizations were reported for six children (median age, 11.7 years; female, 5 [83.3%]; comorbidities, 0 [0%]; median length of hospital stay, 6 days [min. 1, max. 100]). Reported symptoms leading to hospitalization related to the neurological, gastrointestinal and psychological system (eTable 21). In 5/16 (26.3%) administered vaccination doses were unknown, 1/16 dose administered exceeded the current age-group-specific STIKO recommendation as of May 2023. No child required intensive medical care. No death (mortality, 0%) was reported as well as no case of myocarditis/pericarditis following BNT162b2 administration. Reporting a SAE correlated significantly to female gender (OR, 4.55; 95% CI, 2.10–9.88) and long-term medication (OR, 3.67; 95% CI, 1.39–9.69). Sensitivity Analyses Datasets of vaccinations with missing LOT-number of BNT162b2 (22.1%) could be verified to limited extent. As some participants may not have been able to identify the LOT number in the vaccination document sensitivity analysis were performed using χ 2 -test to compare this data to datasets with valid LOT-numbers. No significant differences were found. As the available data is based on a long observation period, they were also reviewed with regards to correlations between the COVID-19 vaccination period and the frequency of reported vaccination reactions. Therefore, children vaccinated after October 1st, 2021 represented an internal control. In addition, binary logistic regression analyses adapted for age, sex, and comorbidities identified no significant correlation between reporting a verified LOT-number or the COVID-19 vaccination period and the frequency of vaccination reactions. Discussion The CoVacU18 retrospective cohort study, based on self-reports on long-term safety of BNT162b2 vaccine in children < 18 years, shows in 98% of included children no to mild symptoms after (repeated) BNT162b2 applications during a median observation period of 524 days. The rate of most common symptoms reported is largely in line with other published results but currently available studies contain limited information about the vulnerable group of children, are restricted to observation periods of a maximum of 6 month after basic immunization or focus on the safety of the vaccine in patients with specific underlying diseases ( 8 , 9 , 19 – 23 ). Therefore, to our knowledge, the CoVacU18 study is currently the only study that provides an initial insight into the long-term safety of BNT162b2 over a retrospective observation period of more than 1.5 years after the 1st dose of BNT162b2 including all age groups < 18 years. Previous safety signals apply to the development of post-vaccination myocarditis/pericarditis, which have been observed more frequently in boys aged 12–17 years within 14 days after the second vaccination. No case of myocarditis/pericarditis was reported by participants included in this study. This complication occurs at an incidence of 48 up to 62.8 per million persons, so no case was expected to be affected in the observed cohort ( 3 , 14 , 15 ). However, rare cases were reported of symptoms lasted ≥ 90 days or additionally were ongoing at the time of survey and thus represented a health restriction. It is noticeable that girls were significantly more frequently affected and that most affected children were ≥ 5 years old. As other studies have already described that females are more frequently and severe affected by side effects of mRNA-based vaccinations, the results of our study are consistent with the finding that gender-specific differences exist in the tolerability and safety of mRNA-based BNT162b2 vaccine ( 16 – 18 ). The calculated SAE rate of 1.4% does not exceed other reported rates ranging from 0.01–1.7% ( 8 , 9 , 22 – 24 ). It is striking that reported long-lasting symptoms in our collected data (headache, dizziness, abdominal pain, diarrhea, anxiety, concentration and sleep disorders etc.) are included in the definition of Long-COVID disease ( 25 ). No causality can be verified based on the available data, so it is questionable whether the reported symptoms could be caused by the vaccine itself, by undetected SARS-CoV-2 infections or pandemic-independent factors. Regarding to long-lasting psychological complaints, the COVID-19-pandemic itself could be a strong confounder.​ We could not find other publications that considered long-term symptoms after BNT162b2 administration as SAE, so there is no comparable data. Compared to the CoVacU5-study, slightly differences regarding to the results of the Active-Comparator-Analysis could be explained by the subdivision of the age groups for < 5-year-olds. Another difference revealed by the age group classification is the significantly less frequent use of medication after BNT162b2 vaccination < 2 year-olds. The calculated OR of the symptom categories are comparatively higher in older age groups and is therefore consistent with the observation that older children develop vaccination reactions more frequently than younger children ( 8 , 9 , 23 , 24 ). The vaccine may be more reactogenic in older children or the deviations may be explained by the ability to communicate and localize symptoms. Strength and Limitations The strength of this study lies in the large number of participants, and in the observation period over one year after the first COVID-19 vaccination. Other studies refer to an observation period of up to six months after completion of basic immunization ( 8 , 9 ). Several caveats of this study should be considered. The data analyzed were based on the recall of participants. Some reported vaccinations date back several months, so there is a risk of recall bias. A potential recall bias was reduced by the fact, that observed non-SARS-CoV-2 vaccinations had a maximum interval of 3 months to the BNT162b2 vaccination. However, no correlation could be detected by sensitivity analysis so this influence remains limited. Due to the retrospective design, the available data do not correspond to a real-time documentation. A temporal relationship between the occurrence of symptoms and the vaccination cannot be confirmed with certainty. For example, concurrent infections, which were present but potentially undiagnosed at the time of vaccinations could potentially have caused the reported symptoms. Compared with results from prospective approval studies, our results are very similar with regard to the frequency of reported symptoms ( 8 , 9 , 23 ). Further, the low response rate of 25% (yielding 21% valid responses) may be due to inviting-emails not containing the survey content for privacy reasons or going unnoticed as spam messages, or that public interest in the topic of mRNA-based COVID-19 vaccination is waning. Feedback from invited participants and medical practices indicates that some participants were registered in two databases (Initiative BildungAberSicher and the vaccination center) and were therefore contacted by two independent cooperation partners. This could affect an estimated maximum of 1400 E-Mail addresses. For data protection reasons, however, we are unable to verify this assumption. Taking this aspect into account, the actual response rate would be 27.4%. There is also a risk for selection bias that may result in underrepresentation in the individual age groups, considering current vaccination rates. The actual frequency of vaccination reactions in individual categories may therefore differ. There is still a potential risk of tampering, which has been minimized by sending invitations to registered E-Mail-addresses, using individual authentication codes and the availability of the BNT162b2 LOT-numbers as well as exclude potential duplicate entries by overlap in demographic data. At the time of our survey, the pandemic has been declared over by both the WHO and the German health minister. There were no longer any reasons of political conflicts in society. We therefore estimate the risk of manipulation to be lower than at the time of the CoVacU5 study. Conclusion To our knowledge this is the first long-term observational study on the safety of mRNA-based COVID-19 vaccine BNT162b2 in children aged 0-17 years. No to mild symptoms were reported occurring after BNT162b2 vaccination in most children but in rare cases (1.4%) symptoms persisted for ≥90 days. Reasons explaining the occurrence of these health restrictions remains unclear from available data. Question of causality should further be scrutinized in future prospective studies. Declarations Statement and Declarations: The authors have no relevant financial or non-financial interests to disclose. Acknowledgments : The authors are thankful to all participating vaccination centers and respondents. We acknowledge the nonprofit assistance for participant recruitment provided by the BildungAberSicher initiative and by Anke Böhnke, MD (Frauenarztpraxis, Berlin, Germany), Joachim Moersdorf, MD (Hausarztpraxis Dres. Moersdorf & Herschel, Pretzfeld, Germany), Johannes Püschel, MD (Hausarztzentrum Greven, Greven, Germany) and Rainer Blasczyk, MD (Medizinische Hochschule Hannover, Hannover, Germany). No one was compensated for their work. We are also thankful for the financial support of our study by the University of Witten/ Herdecke, Witten, Germany. Funding: This study was funded by the University of Witten/Herdecke, Witten, Germany and the University Medical Center, Technische Universität Dresden, Dresden, Germany. Conflicts of interest: The authors have no relevant financial or non-financial interests to disclose. Ethics approval: The approval of this study project was given by the Ethical Committee of the University of Witten/Herdecke e. V. (Application number S-61/2023). Written informed consent to participate in this study and for subsequent data processing was provided by the legal guardians of the children. This study follows STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) reporting guidelines. Contributors Statement: Vivien Grieshaber designed the questionnaire, recruited cooperating medical practices, performed statistical analyses, interpreted the data and drafted the initial manuscript. Dr Christoph Strumann had full access to all of the data in the study, takes responsibility for the integrity of the data and the accuracy of data analysis, gave administrative and technical support and critically reviewed and revised the manuscript for important intellectual content. Sarah Holzwarth designed the questionnaire, coordinated and supervised data collection, and critically reviewed and revised the manuscript for important intellectual content. Dr Nicole Toepfner conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed and revised the manuscript for important intellectual content. Drs Wolfang C.G. von Meißner, Nikos Konstantopoulos and Martina von Poblotzki recruited participants, analysed and interpreted the data and critically reviewed and revised the manuscript for important intellectual content. Dr Kai O. Hensel analysed and interpreted the data and critically reviewed and revised the manuscript for important intellectual content. Dr Matthias B. Moor conceptualized and designed the study, designed the questionnaire and critically reviewed and revised the manuscript for important intellectual content. Dr Cho-Ming-Chao concepted and designed the study, coordinated and supervised data collection, had full access to all of the data in the study, takes responsibility for the integrity of the data and the accuracy of data analysis, gave administrative, technical and material support, critically reviewed and revised the manuscript for important intellectual content and had the supervision of the project. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. References Toepfner N, von Meissner WCG, Strumann C, Drinka D, Stuppe D, Jorczyk M, et al. Comparative Safety of the BNT162b2 Messenger RNA COVID-19 Vaccine vs Other Approved Vaccines in Children Younger Than 5 Years. JAMA Netw Open. 2022;5(10):e2237140. Bundesministerium für Gesundheit. (2023, April). Übersicht zum Impfstatus 2023 - COVID-19-Impfung in Deutschland bis zum 8. April 2023. Impfdashbord.de. Retrieved November 23, 2023, from https://impfdashboard.de/ . Piechotta V, Koch J, Berner R, Bogdan C, Burchard G, Heininger U et al. Aktualisierung der COVID-19-Impfempfehlung in den allgemeinen Empfehlungen der STIKO 2024 und die dazugehörige wissenschaftliche Begründung. Epid Bull. 2024; 2:3–19| 10.25646/11894 . 2024. Tezer H, Deniz M. From asymptomatic to critical illness - different clinical manifestations of COVID-19 in children. Turk J Med Sci. 2021;51(SI–1):3262–72. Di Pietro GM, Ronzoni L, Meschia LM, Tagliabue C, Lombardi A, Pinzani R, et al. SARS-CoV-2 infection in children: A 24 months experience with focus on risk factors in a pediatric tertiary care hospital in Milan, Italy. Front Pediatr. 2023;11:1082083. Castagnoli R, Votto M, Licari A, Brambilla I, Bruno R, Perlini S, et al. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review. JAMA Pediatr. 2020;174(9):882–9. Waghmare A, Hijano DR. SARS-CoV-2 Infection and COVID-19 in Children. Clin Chest Med. 2023;44(2):359–71. Munoz FM, Sher LD, Sabharwal C, Gurtman A, Xu X, Kitchin N, et al. Evaluation of BNT162b2 Covid-19 Vaccine in Children Younger than 5 Years of Age. N Engl J Med. 2023;388(7):621–34. Walter EB, Talaat KR, Sabharwal C, Gurtman A, Lockhart S, Paulsen GC, et al. Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age. N Engl J Med. 2022;386(1):35–46. Hu M, Wong HL, Feng Y, Lloyd PC, Smith ER, Amend KL, et al. Safety of the BNT162b2 COVID-19 Vaccine in Children Aged 5 to 17 Years. JAMA Pediatr. 2023;177(7):710–7. Strumann C, Ranzani OT, Moor J, Berner R, Toepfner N, Chao CM et al. Vaccine effectiveness of BNT162b2 mRNA Covid-19 vaccine in children under 5 years. J Clin Invest. 2023. Tartof SY, Frankland TB, Slezak JM, Puzniak L, Ackerson BK, Jodar L et al. Receipt of BNT162b2 Vaccine and COVID-19 Ambulatory Visits in US Children Younger Than 5 Years. JAMA. 2023. Bundesinstitut für Arzneimittel und Medizinprodukte. Drug Information System. Retrieved. November, 2023,from: https://portal.dimdi.de/amguifree/chp/search.xhtml . Witberg G, Magen O, Hoss S, Talmor-Barkan Y, Richter I, Wiessman M, et al. Myocarditis after BNT162b2 Vaccination in Israeli Adolescents. N Engl J Med. 2022;387(19):1816–7. Dionne A, Sperotto F, Chamberlain S, Baker AL, Powell AJ, Prakash A, et al. Association of Myocarditis With BNT162b2 Messenger RNA COVID-19 Vaccine in a Case Series of Children. JAMA Cardiol. 2021;6(12):1446–50. Mori M, Yokoyama A, Shichida A, Sasuga K, Maekawa T, Moriyama T. Impact of Sex and Age on mRNA COVID-19 Vaccine-Related Side Effects in Japan. Microbiol Spectr. 2022;10(6):e0130922. Green MS, Peer V, Magid A, Hagani N, Anis E, Nitzan D. Gender Differences in Adverse Events Following the Pfizer-BioNTech COVID-19 Vaccine. Vaccines (Basel). 2022;10(2). Moor J, Toepfner N, Wolfgang CG, von Meißner R, Berner MB, Moor. Karolina Kublickiene, Christoph Strumann, Cho-Ming Chao. Sex differences in symptoms following the administration of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years of age in Germany (CoVacU5): a retrospective cohort study. medRxiv 2024.03.08.24303999. 2024. Goshen-Lago T, Waldhorn I, Holland R, Szwarcwort-Cohen M, Reiner-Benaim A, Shachor-Meyouhas Y, et al. Serologic Status and Toxic Effects of the SARS-CoV-2 BNT162b2 Vaccine in Patients Undergoing Treatment for Cancer. JAMA Oncol. 2021;7(10):1507–13. Heshin-Bekenstein M, Ziv A, Toplak N, Lazauskas S, Kadishevich D, Ben-Nun Yaari E et al. Safety and Immunogenicity Following the Second and Third Doses of the BNT162b2 mRNA COVID-19 Vaccine in Adolescents with Juvenile-Onset Autoimmune Inflammatory Rheumatic Diseases: A Prospective Multicentre Study. Vaccines (Basel). 2023;11(4). Valentini D, Cotugno N, Scoppola V, Di Camillo C, Colagrossi L, Manno EC et al. Safety and Long-Term Immunogenicity of BNT162b2 Vaccine in Individuals with Down Syndrome. J Clin Med. 2022;11(3). Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383(27):2603–15. Frenck RW Jr., Klein NP, Kitchin N, Gurtman A, Absalon J, Lockhart S, et al. Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents. N Engl J Med. 2021;385(3):239–50. Matson RP, Niesen MJM, Levy ER, Opp DN, Lenehan PJ, Donadio G, et al. Paediatric safety assessment of BNT162b2 vaccination in a multistate hospital-based electronic health record system in the USA: a retrospective analysis. Lancet Digit Health. 2023;5(4):e206–16. (2024). COVID-19 – Long COVID. Centers for Disease Control and Prevention, Retrieved. March 14, May 13, 2024, from https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html . Additional Declarations No competing interests reported. Supplementary Files SupplementaryOnlineContentfinal.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4566186","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":319523605,"identity":"a38a3901-8002-4c10-b08c-ddfb52455b65","order_by":0,"name":"Vivien Grieshaber","email":"","orcid":"","institution":"Witten/Herdecke University","correspondingAuthor":false,"prefix":"","firstName":"Vivien","middleName":"","lastName":"Grieshaber","suffix":""},{"id":319523606,"identity":"7f9cf3f0-878e-4c8b-be78-60b95c034b09","order_by":1,"name":"Christoph Strumann","email":"","orcid":"","institution":"University of Lübeck","correspondingAuthor":false,"prefix":"","firstName":"Christoph","middleName":"","lastName":"Strumann","suffix":""},{"id":319523607,"identity":"fcc68fc4-7b0e-4225-a832-597f2e69eb45","order_by":2,"name":"Sarah Holzwarth","email":"","orcid":"","institution":"University Hospital Carl Gustav Carus","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"","lastName":"Holzwarth","suffix":""},{"id":319523608,"identity":"df4b4c72-75b0-41ca-862c-04526dcdce33","order_by":3,"name":"Nicole Toepfner","email":"","orcid":"","institution":"University Hospital Carl Gustav Carus","correspondingAuthor":false,"prefix":"","firstName":"Nicole","middleName":"","lastName":"Toepfner","suffix":""},{"id":319523610,"identity":"fc334d72-81dc-411e-8644-b261232387a4","order_by":4,"name":"Wolfgang C. 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Participants\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4566186/v1/bbdf7237f9af5303f48929ee.jpg"},{"id":59964949,"identity":"3502f3eb-22e1-4e53-8a64-8da896a18b29","added_by":"auto","created_at":"2024-07-10 01:54:29","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":47014,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 2 A:\u003c/strong\u003e Frequency of reported symptoms After the First Three Doses of Monovalent BNT162b2 Vaccination, Age 0-20 months\u003c/p\u003e","description":"","filename":"2a.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4566186/v1/c334eb9275c0aaee062136dd.jpg"},{"id":59964947,"identity":"ec639624-9584-4b08-8bd2-a817e382918f","added_by":"auto","created_at":"2024-07-10 01:54:29","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":46724,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 2 B:\u003c/strong\u003e Frequency of Reported Symptoms After the First Three Doses of Monovalent BNT162b2 Vaccination, Age 2-4 years\u003c/p\u003e","description":"","filename":"2b.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4566186/v1/3eb769bd80b0926386903092.jpg"},{"id":59964950,"identity":"0580f34e-89e4-48ea-a5fd-525c32bb7a6c","added_by":"auto","created_at":"2024-07-10 01:54:29","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":49812,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 2 C:\u003c/strong\u003e Frequency of Reported Symptoms After the First Three Doses of Monovalent BNT162b2 Vaccination, Age 5-11 years\u003c/p\u003e","description":"","filename":"2c.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4566186/v1/065b751e50d1263d9c2f8482.jpg"},{"id":59964953,"identity":"06f67675-744b-4fbc-952d-2ea31446b0a6","added_by":"auto","created_at":"2024-07-10 01:54:29","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":51365,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 2 D:\u003c/strong\u003eFrequency of Reported Symptoms After the First Three Doses of Monovalent BNT162b2 Vaccination, Age 12-17 years\u003c/p\u003e","description":"","filename":"2d.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4566186/v1/d9202686a67a7239e1abdf97.jpg"},{"id":59967108,"identity":"2b44091b-ba36-4835-a81d-fcee45610a24","added_by":"auto","created_at":"2024-07-10 02:18:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1377586,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4566186/v1/49ac3463-2ab5-4a23-bc38-c54b396f446e.pdf"},{"id":59965927,"identity":"f7e6fad9-166f-45a6-a178-1ac80ea2f384","added_by":"auto","created_at":"2024-07-10 02:02:29","extension":"pdf","order_by":12,"title":"","display":"","copyAsset":false,"role":"supplement","size":880319,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryOnlineContentfinal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4566186/v1/04d3912e9cda9c2374638b2f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"CoVacU18-Study: Long-Term Safety of BNT162b2 in Children under 18 Years in Germany","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe mRNA-based COVID-19 vaccine BNT612b2 was approved with a delay for children\u0026thinsp;\u0026lt;\u0026thinsp;12 years due to a lack of data on tolerability in this age group. Since October 2022 children from the age of 6 months could also be vaccinated on-label in Germany. The circumstances of off-label vaccinations in children in Germany have been described in the previous CoVacU5-study (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Until the day of April 8, 2023, 22.4% of 5-11-year-olds and only 0.1% of under 4-years-old children received\u0026thinsp;\u0026ge;\u0026thinsp;1 COVID-19 vaccination in Germany. In contrast, 69.9% of 12-17-year-olds received basic immunization (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAs of January 2024 the BNT162b2-administration is recommended by the Standing Commission on Vaccination (STIKO) to be given as a three-dose series in children aged six months to four years (3\u0026micro;g/dose) and in a two-dose series in children aged 5\u0026ndash;11 years (10 \u0026micro;g/dose) as well as in adolescents (30\u0026micro;g/dose) (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Due to the mostly mild course of SARS-CoV-2 infections in children, the recommendations refer to children with underlying diseases that are associated with an increased risk of severe disease progression and complications (\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Risk factors for a severe course of COVID-19 in childhood have been identified in several studies and included prematurity, presence of coinfections and comorbidities (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The decision for or against the COVID-19 vaccination remains a present and relevant issue, especially for parents whose children are meeting risk factors or are in regular contact with people at risk. The mRNA-based COVID-19 vaccine BNT162b2 has proven to be well tolerated in children\u0026thinsp;\u0026ge;\u0026thinsp;6 months but safety signals have emerged due to an increased incidence of myocarditis and pericarditis following vaccination (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). The risk of suffering SARS-CoV-2 infection or visiting a healthcare facility due to the infection has been demonstrably reduced by the vaccination (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Despite the good prognosis for healthy children who suffer SARS-CoV-2 infection, the assessment of long-term tolerability of the mRNA-based COVID-19 vaccine remains of great importance, but to our knowledge, there have been no studies to date. The previous CoVacU5 study already registered significant differences between the occurrence of certain symptom categories compared to non-SARS-CoV-2 vaccinations in \u0026lt;\u0026thinsp;5-year-olds (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). We conducted the present study to further elucidate long-term tolerability after (repeated) BNT162b2 administration, filling a current knowledge gap. The ensuing information may contribute to characterize the long-term safety and risk profile of mRNA based BNT162b2 vaccine and to detect rare complications that may have escaped previous reports from smaller datasets or less systematic follow-ups.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis study was designed as a retrospective longitudinal cohort study. We evaluated the safety and tolerability of BNT162b2 mRNA-based COVID-19 vaccine (Comirnaty, Comirnaty Original/Omicron BA.1 or BA.4\u0026ndash;5) in children vaccinated in Germany\u0026thinsp;\u0026lt;\u0026thinsp;18 years of age. All vaccinations considered were administered on a voluntary basis before the study was planned. The central requirement for vaccination was that parents or legal representatives provided written individual informed consent to the vaccination and were informed by the attending physicians about potential adverse effects and in case of need about the liability of off-label medicine use under German law. The attending physicians were obliged by the Infection Protection Act to report any vaccination reaction exceeding the usual level/any severe adverse effects experienced by the children to the responsible public health department, regardless of the current study. The present study was based on an online questionnaire addressed to the parents/legal representatives of vaccinated children. Eligible participants were identified from electronic databases of ten cooperating outpatient medical practices and the nationwide layperson-initiated SARS-CoV-2 vaccination social media program \u003cem\u003eBildungAberSicher\u003c/em\u003e in Germany. During the study period of May 25th to July 11th, 2023 legal guardians were contacted three times via email-addresses registered in the database to complete the online-survey. Participation was only possible using an individual authentication code. The study database was closed on July 11th, 2023 and data were extracted for analysis in a pseudonymous mode. Exclusion criteria were duplicate records regarding to the variables \u0026ldquo;age\u0026rdquo;, \u0026ldquo;sex\u0026rdquo;, \u0026ldquo;weight\u0026rdquo;, \u0026ldquo;height\u0026rdquo; and the authentication code without indication that children were twins/triplets. Datasets without valid authentication code as proof of invitation, and SARS-CoV-2 vaccinations with exclusively other than BNT162b2 (Comirnaty, Comirnaty Original/Omicron BA.1 or BA.4\u0026ndash;5) were excluded. Serious Adverse Events (SAE) were defined as any event resulted in hospitalization or death due to the symptoms described and a symptom duration\u0026thinsp;\u0026ge;\u0026thinsp;90 days.\u003c/p\u003e \u003cp\u003eThe approval of this study project was given by the Ethical Committee of the University of Witten/Herdecke e. V. (Application number S-61/2023). Written informed consent to participate in this study and for subsequent data processing was provided by the legal guardians of the children. This study follows STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) reporting guidelines.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy Procedure\u003c/h2\u003e \u003cp\u003eAll study data were collected using REDCap (Research Electronic Data Capture). Data were stored at the Koordinierungszentrum f\u0026uuml;r Klinische Studien Dresden (KKS) at the University Medical Center Dresden, TU Dresden, Germany. The online survey was designed to be completed within 30 minutes retrospectively to report on vaccination reactions and was pretested in 10 pilot test runs. Demographic data were collected including age, gender, weight, height, number of COVID-19 vaccinations received, comorbidities, and concurrent medications. Vaccination reactions were queried in eleven symptom categories by close-ended questions and free-test responses. The symptom categories were the following: injection-site symptoms; general reactions; fever; any symptoms of the musculoskeletal, cardiovascular, pulmonary, otolaryngological, gastrointestinal, neurological, psychological or dermatological system including lymph node reactions. Radio-button choice was used to record individual symptoms, which were characterized in terms of initial onset after vaccination, duration and any required measures using close-ended questions. A self-assessment of the medical threat was recorded on a scale of 0\u0026ndash;10 (0\u0026thinsp;=\u0026thinsp;not threatening, 10\u0026thinsp;=\u0026thinsp;very threatening). Free-text responses were available in all categories if individual vaccination reactions were not represented in multiple-choice response options. To perform an active comparator analysis, the tolerability of common non-SARS-CoV-2 vaccines, administered in the same children within three months before or after BNT162b2 administration, was surveyed for all symptom categories. Free-text responses were queried for the German terms for myocarditis/pericarditis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe primary outcome was the frequency of self-reported categorized symptoms after BTN162b2 administration (Comirnaty, Comirnaty Original/Omicron BA.1 or BA.4\u0026ndash;5) stratified by age group (0\u0026ndash;23 months, 2\u0026ndash;4 years, 5\u0026ndash;11 years, 12\u0026ndash;17 years) compared to common non-SARS-CoV-2 vaccines.\u003c/p\u003e \u003cp\u003eThe secondary outcomes were onset, duration and self-assessed medical threat of symptoms occurring after BNT162b2 administration as well as measures taken. Furthermore, the frequencies of vaccination reactions compared between mono- and bivalent BNT162b2 vaccines were of interest.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using IBM SPSS Statistics, version 29.0.0.0 (241). Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Odds ratio (OR) were calculated using the Wald method and from logistic regression models adjusted for age group (0\u0026ndash;23 months, 2\u0026ndash;4 years, 5\u0026ndash;11 years, 12\u0026ndash;17 years), sex, weight, height and comorbidities. Logistic regression models were performed with any symptom or the eleven individual categories of post-vaccination symptoms as dependent variables and BNT162b2 vs. non-SARS-CoV-2 vaccines as variable of interest. Duration and impact of the symptoms were assessed in additional logistic models. Calculated p-values and 95% CI were adjusted using the Bonferroni method.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eFor participant recruitment 15622 invitations were sent to eligible individuals, 3841 responses were received, corresponding to a response rate of 24.6%. The flowchart in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the total number of exclusions and reasons for exclusion.\u003c/p\u003e \u003cp\u003e A total of 3228 children who received at least one dose of BNT162b2 were included in this study (median age, 5.7 years [IQR, 3.4\u0026ndash;9.5]) and observed over a median period of 524 days (IQR, 500\u0026ndash;553 days). Basic immunization (\u0026ge;\u0026thinsp;2 BNT162b2 doses) was administered in 3119 participants (96.6%). Overall, 49.6% were male, 12.3% had an underlying chronic disease and 7.6% were taking permanent medication. Most often reported pre-existing conditions were pulmonary (n\u0026thinsp;=\u0026thinsp;120 [3.7%]), cardiovascular (n\u0026thinsp;=\u0026thinsp;53 [1.6%]) and chromosomal aberrations (n\u0026thinsp;=\u0026thinsp;37 [1.1%]) (eTable 1). Each LOT-number given was examined for authenticity and the validity regarding to the vaccination date via the drug information system of the Federal Institute for Drugs and Medical Devices in Germany (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). LOT-numbers were also used to check vaccine variant (mono- or bivalent) and to correct information provided if necessary. Overall, 9510 vaccinations were examined, and a valid LOT-number was reported for 76.6%, no LOT-number was reported for 22.1%.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of the Cohort Related to the Chronological BNT162b2 Vaccinations One Through Six, n/N (%)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1st BNT vaccination\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2nd BNT vaccination\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3rd BNT vaccination\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4th BNT vaccination\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5th BNT vaccination\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6th BNT vaccination\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3204\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1898\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e227\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1595 (49.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1555 (49.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e963 (50.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e522 (52.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e113 (49.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e19 (52.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1600 (49.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1556 (49.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e927 (48.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e475 (47.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e112 (49.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16 (44.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, median, y\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;23 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e407 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e369 (11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e144 (7.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0(0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u0026ndash;4 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1006 (31.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e958 (30.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e588 (31.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e295 (29.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e54 (23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8 (21.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u0026ndash;11 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1407 (43.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1381 (44.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e812 (42.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e484 (48.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e123 (54.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e22 (59.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u0026ndash;17 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e360 (11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e379 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e337 (17.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e150 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e40 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5 (14.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 (2.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProportion of bivalent vacci-nations, (BA.1 or BA.4\u0026ndash;5)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e351 (18.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e846 (84.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e210 (92.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e34 (94.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDosage, median (min.; max.), \u0026micro;g\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (1,5; 30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (1,5; 30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (3;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15 (3;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15 (3;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15 (5;30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e441 (13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e432 (13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e128 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComorbidities\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e395 (12.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e381 (12.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e271 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e150 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e36 (15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9 (25.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLong-term medication\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e241 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e234 (7.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e171 (9.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e91 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25 (11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6 (16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eFrequency of Reported Symptoms and Measures Taken After the First Three Wildtype-BNT162b2-Vaccinations\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eReported symptoms following administration of monovalent BNT162b2 (Comirnaty Original) vaccine were descriptively analyzed chronologically, divided into eleven symptom categories and stratified by age group (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-D). Most common symptoms related to local-injection site, general condition, fever and musculoskeletal system. In comparison of the first to third vaccination a decreasing trend in the frequency of local-injection site reactions, fever, general and neurological symptoms after each subsequent vaccination is shown. In contrast, psychological and dermatological events increased in 12-17-year-olds. Adolescents were twice as likely to report neurological symptoms as children aged 5\u0026ndash;11 years. Odds ratio to report\u0026thinsp;\u0026ge;\u0026thinsp;1 symptom was increased if the child was female (OR, 1.34 [95% CI, 1.14\u0026ndash;1.57]) or had an underlying chronic disease (OR, 1.34 [95% CI, 1.05\u0026ndash;1.72]). A maximum of 6.2% received medications such as antipyretics and a maximum of 0.5% received outpatient medical treatment after at least one of three vaccinations. No significant correlation between the frequency of reported vaccine reactions and the applied vaccine dose was found. Post-vaccination symptoms after all analyzed BNT162b2-vaccinations are shown in the Supplement (eTable 2\u0026ndash;17).\u003c/p\u003e \u003ch2\u003eMonovalent and Bivalent BNT162b2 Vaccine in Comparison\u003c/h2\u003e \u003cp\u003eIn a subgroup of 1842 children, the frequency of any reported symptom after receiving the bivalent or monovalent BNT162b2 vaccine was compared. For this purpose, reports of children who received the bivalent BNT162b2 as the 3rd or 4th chronological vaccination for the first time were compared with those who received monovalent BNT162b2 exclusively but in the same sum. The probability of any symptom reported after the bivalent BNT162b2 vaccination was slightly increased (OR, 1.2; 95% CI, 0.92\u0026ndash;1.53 [bivalent vs. monovalent, 3rd chronological vaccination]; OR, 1.15; 95% CI, 0.72\u0026ndash;1.69 [bivalent vs. monovalent, 4th chronological vaccination]) but not significant.\u003c/p\u003e \u003cp\u003eThe frequency of reported symptoms after mono- or bivalent BNT162b2-vaccination were stratified by age group (eTable 18).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eActive Comparator Analysis for BNT162b2 vs. Non-SARS-CoV-2-Vaccinations\u003c/h2\u003e \u003cp\u003eAn active comparator analysis was performed in a subgroup of 1185 children who received at least both a BNT162b2 COVID-19 vaccination and a common non-SARS-CoV-2 vaccination authorized in Germany at a maximum interval of 3 months in the period from January 5th, 2021 to March 31st, 2023. The minimum observation period for both vaccines was 2 months. Overall, information of 7532 BNT162b2 vaccinations and 1764 non-SARS-CoV-2 vaccinations were considered. Results stratified by age group are shown in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-D. The comparison was also performed across all age groups 0\u0026ndash;17 years (eTable 19).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eA: Active-Comparator Analysis of Symptoms Occurring after BNT162b2 and Non-BNT162b2 vaccinations, Age 0\u0026ndash;23 months\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eFrequencies, No./total No. (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eLogistic regression\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBNT162b2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNon-SARS-CoV-2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eDisposition\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical rest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.71 (0.47\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.34 (0.21\u0026ndash;0.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmbulatory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.51 (0.25\u0026ndash;9.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSymptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny symptom reported\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e154/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e134/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.30 (0.93\u0026ndash;1.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e121/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e91/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.58 (1.11\u0026ndash;2.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.12\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e103/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.57 (0.39\u0026ndash;0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.04\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.37 (0.24\u0026ndash;0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMusculoskeletal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.75 (0.16\u0026ndash;3.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.85 (0.28\u0026ndash;2.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOtolaryngological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiovascular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDermatological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.11 (0.61\u0026ndash;15.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003eb\u003c/sup\u003e adjusted for multiple testing by Bonferroni correction. All individuals in the Non-BNT162b2 group had also received at least one dose of BNT162b2 between January 5th ,2021 to March 31,2023 but here reported symptoms occurring after the Non-BNT162b2 are shown.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eB: Active-Comparator Analysis of Symptoms Occurring after BNT162b2 and Non-BNT162b2 vaccinations, Age 2\u0026ndash;4 years\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eFrequencies, No./total No. (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eLogistic regression\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBNT162b2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNon-SARS-CoV-2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eDisposition\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical rest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.58 (1.70\u0026ndash;3.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.30 (0.73\u0026ndash;2.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmbulatory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSymptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny symptom reported\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e239/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.69 (4.77\u0026ndash;9.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e217/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.09 (4.33\u0026ndash;8.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.22 (1.48\u0026ndash;3.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.18 (0.71\u0026ndash;1.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMusculoskeletal system\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.70 (0.95\u0026ndash;7.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.72\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.49 (1.33\u0026ndash;82.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.31\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOtolaryngological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.52 (0.25\u0026ndash;9.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiovascular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.53 (1.48\u0026ndash;90.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.24\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.50 (0.25\u0026ndash;9.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDermatological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1/346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.94 (2.23-128.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.07\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003eb\u003c/sup\u003e adjusted for multiple testing by Bonferroni correction. All individuals in the Non-BNT162b2 group had also received at least one dose of BNT162b2 between January 5th ,2021 to March 31,2023 but here reported symptoms occurring after the Non-BNT162b2 are shown.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eC: Active-Comparator Analysis of Symptoms Occurring after BNT162b2 and Non-BNT162b2 vaccinations, Age 5\u0026ndash;11 years\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eFrequencies, No./total No. (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eLogistic regression\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBNT162b2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNon-SARS-CoV-2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003eDisposition\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical rest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e148/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e2.79 (1.99\u0026ndash;3.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e2.24 (1.37\u0026ndash;3.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmbulatory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSymptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny symptom reported\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e345/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e153/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e4.06 (2.05\u0026ndash;8.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e321/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e144/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e5.28 (3.94\u0026ndash;7.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e130/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e2.89 (2.03\u0026ndash;4.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e2.34 (1.39\u0026ndash;3.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMusculoskeletal system\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e4.06 (2.05\u0026ndash;8.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e12.58 (1.62\u0026ndash;97.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.12\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOtolaryngological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e6.21 (0.74\u0026ndash;52.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e4.08 (0.45\u0026ndash;36.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiovascular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e7.49 (0.90-62.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.72\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e14.86 (4.55\u0026ndash;48.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDermatological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6/450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e5.23 (2.14\u0026ndash;12.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003eb\u003c/sup\u003e adjusted for multiple testing by Bonferroni correction. All individuals in the Non-BNT162b2 group had also received at least one dose of BNT162b2 between January 5th ,2021 to March 31,2023 but here reported symptoms occurring after the Non-BNT162b2 are shown.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eD: Active-Comparator Analysis of Symptoms Occurring after BNT162b2 and Non-BNT162b2 vaccinations, Age 12\u0026ndash;17 years\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eFrequencies, No./total No. (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eLogistic regression\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBNT162b2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNon-SARS-CoV-2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eDisposition\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical rest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.06 (3.05\u0026ndash;12.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.68 (1.49\u0026ndash;14.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmbulatory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSymptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny symptom reported\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.59 (6.28\u0026ndash;25.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.59 (5.01\u0026ndash;18.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.16 (3.77\u0026ndash;17.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.14 (1.32\u0026ndash;28.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.25\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMusculoskeletal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.16 (1.33\u0026ndash;12.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.17\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOtolaryngological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiovascular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.42 (2.39\u0026ndash;26.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDermatological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0/110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN.A.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003eb\u003c/sup\u003e adjusted for multiple testing by Bonferroni correction. All individuals in the Non-BNT162b2 group had also received at least one dose of BNT162b2 between January 5th ,2021 to March 31,2023 but here reported symptoms occurring after the Non-BNT162b2 are shown.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSerious Adverse Events\u003c/h2\u003e \u003cp\u003eOverall, 48 SAEs were reported in 45 children (1.39%). 69% of the affected children were \u0026ge;\u0026thinsp;5 years old. A symptom duration of \u0026ge;\u0026thinsp;90 days (median onset, 1.5 days; median duration at time of survey, 126.5 days) was reported for 41 children, in 22 of these symptoms were still persistent at the time of survey (eTable 20\u0026ndash;21). Long-lasting symptoms involved most often the psychological, neurological and dermatological system (eTable 8\u0026ndash;17). A total of 117 vaccine doses were administered, of which the doses were unknown in 24.7% (29 doses) and the current age-group-specific STIKO recommendations (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) were exceeded in 31.6% (37 doses).\u003c/p\u003e \u003cp\u003eSeven hospitalizations were reported for six children (median age, 11.7 years; female, 5 [83.3%]; comorbidities, 0 [0%]; median length of hospital stay, 6 days [min. 1, max. 100]). Reported symptoms leading to hospitalization related to the neurological, gastrointestinal and psychological system (eTable 21). In 5/16 (26.3%) administered vaccination doses were unknown, 1/16 dose administered exceeded the current age-group-specific STIKO recommendation as of May 2023. No child required intensive medical care. No death (mortality, 0%) was reported as well as no case of myocarditis/pericarditis following BNT162b2 administration.\u003c/p\u003e \u003cp\u003eReporting a SAE correlated significantly to female gender (OR, 4.55; 95% CI, 2.10\u0026ndash;9.88) and long-term medication (OR, 3.67; 95% CI, 1.39\u0026ndash;9.69).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity Analyses\u003c/h2\u003e \u003cp\u003eDatasets of vaccinations with missing LOT-number of BNT162b2 (22.1%) could be verified to limited extent. As some participants may not have been able to identify the LOT number in the vaccination document sensitivity analysis were performed using χ\u003csup\u003e2\u003c/sup\u003e-test to compare this data to datasets with valid LOT-numbers. No significant differences were found. As the available data is based on a long observation period, they were also reviewed with regards to correlations between the COVID-19 vaccination period and the frequency of reported vaccination reactions. Therefore, children vaccinated after October 1st, 2021 represented an internal control. In addition, binary logistic regression analyses adapted for age, sex, and comorbidities identified no significant correlation between reporting a verified LOT-number or the COVID-19 vaccination period and the frequency of vaccination reactions.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe CoVacU18 retrospective cohort study, based on self-reports on long-term safety of BNT162b2 vaccine in children\u0026thinsp;\u0026lt;\u0026thinsp;18 years, shows in 98% of included children no to mild symptoms after (repeated) BNT162b2 applications during a median observation period of 524 days. The rate of most common symptoms reported is largely in line with other published results but currently available studies contain limited information about the vulnerable group of children, are restricted to observation periods of a maximum of 6 month after basic immunization or focus on the safety of the vaccine in patients with specific underlying diseases (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20 CR21 CR22\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Therefore, to our knowledge, the CoVacU18 study is currently the only study that provides an initial insight into the long-term safety of BNT162b2 over a retrospective observation period of more than 1.5 years after the 1st dose of BNT162b2 including all age groups\u0026thinsp;\u0026lt;\u0026thinsp;18 years.\u003c/p\u003e \u003cp\u003ePrevious safety signals apply to the development of post-vaccination myocarditis/pericarditis, which have been observed more frequently in boys aged 12\u0026ndash;17 years within 14 days after the second vaccination. No case of myocarditis/pericarditis was reported by participants included in this study. This complication occurs at an incidence of 48 up to 62.8 per million persons, so no case was expected to be affected in the observed cohort (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). However, rare cases were reported of symptoms lasted\u0026thinsp;\u0026ge;\u0026thinsp;90 days or additionally were ongoing at the time of survey and thus represented a health restriction. It is noticeable that girls were significantly more frequently affected and that most affected children were \u0026ge;\u0026thinsp;5 years old. As other studies have already described that females are more frequently and severe affected by side effects of mRNA-based vaccinations, the results of our study are consistent with the finding that gender-specific differences exist in the tolerability and safety of mRNA-based BNT162b2 vaccine (\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The calculated SAE rate of 1.4% does not exceed other reported rates ranging from 0.01\u0026ndash;1.7% (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). It is striking that reported long-lasting symptoms in our collected data (headache, dizziness, abdominal pain, diarrhea, anxiety, concentration and sleep disorders etc.) are included in the definition of Long-COVID disease (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). No causality can be verified based on the available data, so it is questionable whether the reported symptoms could be caused by the vaccine itself, by undetected SARS-CoV-2 infections or pandemic-independent factors. Regarding to long-lasting psychological complaints, the COVID-19-pandemic itself could be a strong confounder.​\u003c/p\u003e \u003cp\u003eWe could not find other publications that considered long-term symptoms after BNT162b2 administration as SAE, so there is no comparable data.\u003c/p\u003e \u003cp\u003eCompared to the CoVacU5-study, slightly differences regarding to the results of the Active-Comparator-Analysis could be explained by the subdivision of the age groups for \u0026lt;\u0026thinsp;5-year-olds. Another difference revealed by the age group classification is the significantly less frequent use of medication after BNT162b2 vaccination\u0026thinsp;\u0026lt;\u0026thinsp;2 year-olds. The calculated OR of the symptom categories are comparatively higher in older age groups and is therefore consistent with the observation that older children develop vaccination reactions more frequently than younger children (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). The vaccine may be more reactogenic in older children or the deviations may be explained by the ability to communicate and localize symptoms.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eStrength and Limitations\u003c/h2\u003e \u003cp\u003eThe strength of this study lies in the large number of participants, and in the observation period over one year after the first COVID-19 vaccination. Other studies refer to an observation period of up to six months after completion of basic immunization (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeveral caveats of this study should be considered. The data analyzed were based on the recall of participants. Some reported vaccinations date back several months, so there is a risk of recall bias. A potential recall bias was reduced by the fact, that observed non-SARS-CoV-2 vaccinations had a maximum interval of 3 months to the BNT162b2 vaccination. However, no correlation could be detected by sensitivity analysis so this influence remains limited. Due to the retrospective design, the available data do not correspond to a real-time documentation. A temporal relationship between the occurrence of symptoms and the vaccination cannot be confirmed with certainty. For example, concurrent infections, which were present but potentially undiagnosed at the time of vaccinations could potentially have caused the reported symptoms. Compared with results from prospective approval studies, our results are very similar with regard to the frequency of reported symptoms (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurther, the low response rate of 25% (yielding 21% valid responses) may be due to inviting-emails not containing the survey content for privacy reasons or going unnoticed as spam messages, or that public interest in the topic of mRNA-based COVID-19 vaccination is waning. Feedback from invited participants and medical practices indicates that some participants were registered in two databases (Initiative \u003cem\u003eBildungAberSicher\u003c/em\u003e and the vaccination center) and were therefore contacted by two independent cooperation partners. This could affect an estimated maximum of 1400 E-Mail addresses. For data protection reasons, however, we are unable to verify this assumption. Taking this aspect into account, the actual response rate would be 27.4%.\u003c/p\u003e \u003cp\u003eThere is also a risk for selection bias that may result in underrepresentation in the individual age groups, considering current vaccination rates. The actual frequency of vaccination reactions in individual categories may therefore differ. There is still a potential risk of tampering, which has been minimized by sending invitations to registered E-Mail-addresses, using individual authentication codes and the availability of the BNT162b2 LOT-numbers as well as exclude potential duplicate entries by overlap in demographic data. At the time of our survey, the pandemic has been declared over by both the WHO and the German health minister. There were no longer any reasons of political conflicts in society. We therefore estimate the risk of manipulation to be lower than at the time of the CoVacU5 study.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTo our knowledge this is the first long-term observational study on the safety of mRNA-based COVID-19 vaccine BNT162b2 in children aged 0-17 years. No to mild symptoms were reported occurring after BNT162b2 vaccination in most children but in rare cases (1.4%) symptoms persisted for \u0026ge;90 days.\u0026nbsp;Reasons explaining the occurrence of these health restrictions remains unclear from available data. Question of causality should further be scrutinized in future prospective studies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatement and Declarations:\u0026nbsp;\u003c/strong\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e: The authors are thankful to all participating vaccination centers and respondents. We acknowledge the nonprofit assistance for participant recruitment provided by the \u003cem\u003eBildungAberSicher\u003c/em\u003e initiative and by Anke B\u0026ouml;hnke, MD (Frauenarztpraxis, Berlin, Germany), Joachim Moersdorf, MD (Hausarztpraxis Dres. Moersdorf \u0026amp; Herschel, Pretzfeld, Germany), Johannes P\u0026uuml;schel, MD (Hausarztzentrum Greven, Greven, Germany) and Rainer Blasczyk, MD (Medizinische Hochschule Hannover, Hannover, Germany). No one was compensated for their work. We are also thankful for the financial support \u0026nbsp;of our study by the University of Witten/ Herdecke, Witten, Germany.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis study was funded by the University of Witten/Herdecke, Witten, Germany and the University Medical Center, Technische Universit\u0026auml;t Dresden, Dresden, Germany.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest:\u0026nbsp;\u003c/strong\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u0026nbsp;\u003c/strong\u003eThe approval of this study project was given by the Ethical Committee of the University of Witten/Herdecke e. V. (Application number S-61/2023). \u0026nbsp;Written informed consent to participate in this study and for subsequent data processing was provided by the legal guardians of the children. This study follows STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) reporting guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributors Statement:\u0026nbsp;\u003c/strong\u003eVivien Grieshaber designed the questionnaire, recruited cooperating medical practices, performed statistical analyses, interpreted the data and drafted the initial manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Dr Christoph Strumann had full access to all of the data in the study, takes responsibility for the integrity of the data and the accuracy of data analysis, gave administrative and technical support and critically reviewed and revised the manuscript for important intellectual content.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Sarah Holzwarth designed the questionnaire, coordinated and supervised data collection, and critically reviewed and revised the manuscript\u0026nbsp;for important intellectual content.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Dr Nicole Toepfner conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed and revised the manuscript for important intellectual content.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Drs Wolfang C.G. von Mei\u0026szlig;ner, Nikos Konstantopoulos and Martina von Poblotzki recruited participants, analysed and interpreted the data and critically reviewed and revised the manuscript for important intellectual content.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Dr Kai O. Hensel analysed and interpreted the data and critically reviewed and revised the manuscript for important intellectual content.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Dr Matthias B. Moor\u0026nbsp;conceptualized and designed the study, designed the questionnaire and critically reviewed and revised the manuscript for important intellectual content.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Dr Cho-Ming-Chao concepted and designed the study, coordinated and supervised data collection, had full access to all of the data in the study, takes responsibility for the integrity of the data and the accuracy of data analysis, gave administrative, technical and material support, critically reviewed and revised the manuscript for important intellectual content and had the supervision of the project.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eToepfner N, von Meissner WCG, Strumann C, Drinka D, Stuppe D, Jorczyk M, et al. Comparative Safety of the BNT162b2 Messenger RNA COVID-19 Vaccine vs Other Approved Vaccines in Children Younger Than 5 Years. JAMA Netw Open. 2022;5(10):e2237140.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBundesministerium f\u0026uuml;r Gesundheit. (2023, April). \u003cem\u003e\u0026Uuml;bersicht zum Impfstatus 2023\u003c/em\u003e - \u003cem\u003eCOVID-19-Impfung in Deutschland bis zum 8. April 2023.\u003c/em\u003e Impfdashbord.de. Retrieved November 23, 2023, from \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://impfdashboard.de/\u003c/span\u003e\u003cspan address=\"https://impfdashboard.de/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePiechotta V, Koch J, Berner R, Bogdan C, Burchard G, Heininger U et al. Aktualisierung der COVID-19-Impfempfehlung in den allgemeinen Empfehlungen der STIKO 2024 und die dazugeh\u0026ouml;rige wissenschaftliche Begr\u0026uuml;ndung. Epid Bull. 2024; 2:3\u0026ndash;19|\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.25646/11894\u003c/span\u003e\u003cspan address=\"10.25646/11894\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTezer H, Deniz M. From asymptomatic to critical illness - different clinical manifestations of COVID-19 in children. Turk J Med Sci. 2021;51(SI\u0026ndash;1):3262\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDi Pietro GM, Ronzoni L, Meschia LM, Tagliabue C, Lombardi A, Pinzani R, et al. SARS-CoV-2 infection in children: A 24 months experience with focus on risk factors in a pediatric tertiary care hospital in Milan, Italy. Front Pediatr. 2023;11:1082083.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCastagnoli R, Votto M, Licari A, Brambilla I, Bruno R, Perlini S, et al. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review. JAMA Pediatr. 2020;174(9):882\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWaghmare A, Hijano DR. SARS-CoV-2 Infection and COVID-19 in Children. Clin Chest Med. 2023;44(2):359\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMunoz FM, Sher LD, Sabharwal C, Gurtman A, Xu X, Kitchin N, et al. Evaluation of BNT162b2 Covid-19 Vaccine in Children Younger than 5 Years of Age. N Engl J Med. 2023;388(7):621\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWalter EB, Talaat KR, Sabharwal C, Gurtman A, Lockhart S, Paulsen GC, et al. Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age. N Engl J Med. 2022;386(1):35\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHu M, Wong HL, Feng Y, Lloyd PC, Smith ER, Amend KL, et al. Safety of the BNT162b2 COVID-19 Vaccine in Children Aged 5 to 17 Years. JAMA Pediatr. 2023;177(7):710\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStrumann C, Ranzani OT, Moor J, Berner R, Toepfner N, Chao CM et al. Vaccine effectiveness of BNT162b2 mRNA Covid-19 vaccine in children under 5 years. J Clin Invest. 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTartof SY, Frankland TB, Slezak JM, Puzniak L, Ackerson BK, Jodar L et al. Receipt of BNT162b2 Vaccine and COVID-19 Ambulatory Visits in US Children Younger Than 5 Years. JAMA. 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBundesinstitut f\u0026uuml;r Arzneimittel und Medizinprodukte. Drug Information System. Retrieved. November, 2023,from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://portal.dimdi.de/amguifree/chp/search.xhtml\u003c/span\u003e\u003cspan address=\"https://portal.dimdi.de/amguifree/chp/search.xhtml\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWitberg G, Magen O, Hoss S, Talmor-Barkan Y, Richter I, Wiessman M, et al. Myocarditis after BNT162b2 Vaccination in Israeli Adolescents. N Engl J Med. 2022;387(19):1816\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDionne A, Sperotto F, Chamberlain S, Baker AL, Powell AJ, Prakash A, et al. Association of Myocarditis With BNT162b2 Messenger RNA COVID-19 Vaccine in a Case Series of Children. JAMA Cardiol. 2021;6(12):1446\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMori M, Yokoyama A, Shichida A, Sasuga K, Maekawa T, Moriyama T. Impact of Sex and Age on mRNA COVID-19 Vaccine-Related Side Effects in Japan. Microbiol Spectr. 2022;10(6):e0130922.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGreen MS, Peer V, Magid A, Hagani N, Anis E, Nitzan D. Gender Differences in Adverse Events Following the Pfizer-BioNTech COVID-19 Vaccine. Vaccines (Basel). 2022;10(2).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoor J, Toepfner N, Wolfgang CG, von Mei\u0026szlig;ner R, Berner MB, Moor. Karolina Kublickiene, Christoph Strumann, Cho-Ming Chao. Sex differences in symptoms following the administration of BNT162b2 mRNA Covid-19 Vaccine in Children below 5 Years of age in Germany (CoVacU5): a retrospective cohort study. medRxiv 2024.03.08.24303999. 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoshen-Lago T, Waldhorn I, Holland R, Szwarcwort-Cohen M, Reiner-Benaim A, Shachor-Meyouhas Y, et al. Serologic Status and Toxic Effects of the SARS-CoV-2 BNT162b2 Vaccine in Patients Undergoing Treatment for Cancer. JAMA Oncol. 2021;7(10):1507\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeshin-Bekenstein M, Ziv A, Toplak N, Lazauskas S, Kadishevich D, Ben-Nun Yaari E et al. Safety and Immunogenicity Following the Second and Third Doses of the BNT162b2 mRNA COVID-19 Vaccine in Adolescents with Juvenile-Onset Autoimmune Inflammatory Rheumatic Diseases: A Prospective Multicentre Study. Vaccines (Basel). 2023;11(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValentini D, Cotugno N, Scoppola V, Di Camillo C, Colagrossi L, Manno EC et al. Safety and Long-Term Immunogenicity of BNT162b2 Vaccine in Individuals with Down Syndrome. J Clin Med. 2022;11(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePolack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383(27):2603\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrenck RW Jr., Klein NP, Kitchin N, Gurtman A, Absalon J, Lockhart S, et al. Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents. N Engl J Med. 2021;385(3):239\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatson RP, Niesen MJM, Levy ER, Opp DN, Lenehan PJ, Donadio G, et al. Paediatric safety assessment of BNT162b2 vaccination in a multistate hospital-based electronic health record system in the USA: a retrospective analysis. Lancet Digit Health. 2023;5(4):e206\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e(2024). \u003cem\u003eCOVID-19 \u0026ndash; Long COVID.\u003c/em\u003e Centers for Disease Control and Prevention, Retrieved. March 14, May 13, 2024, from \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html\u003c/span\u003e\u003cspan address=\"https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"mRNA vaccine, BNT162b2, Safety, Children","lastPublishedDoi":"10.21203/rs.3.rs-4566186/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4566186/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRetrospective evaluation of long-term safety of BNT162b2 in children \u0026lt; 18 years in Germany compared to non-SARS-CoV-2 vaccines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis investigator initiated longitudinal cohort study retrospectively assessed the long-term safety of BNT162b2 using an online questionnaire addressed to parents of vaccinated children. Between May 25th and July 11th we contacted 15423 E-Mail-addresses registered in databases of vaccination centre. Inclusion criteria were at least one BNT162b2 vaccination after October 1st, 2021 \u0026lt; 18 years of age and using a valid authentication code. An active comparator analysis was performed to compare BNT162b2 to non-SARS-CoV-2 vaccines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e3228 children (median age, 5.7 [IQR, 3.4–9.5]; male, 49.6%) who received ≥ 1 dose of BNT162b2 \u0026lt; 18 years were followed up for a median of 524 days (IQR, 500–553 days). Across all age groups, the active-comparator analysis revealed significantly increased rates of post-vaccination symptoms in 10 of 11 categories occurring after BNT162b2 compared to non-SARS-CoV-2 vaccines. In 41 cases symptom duration ≥ 90 days are reported and most frequently affected the neurological, psychological and dermatological system. Relative probability of reporting a serious adverse event was significantly increased if participants were female (OR, 4.55; 95% CI, 2.10–9.88) or took long-term medication (OR, 3.67; 95% CI, 1.39–9.69). No causality can be verified based on the available data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBNT162b2 is well tolerated by 98% of children, but specific symptoms occur significantly more frequently than in non-SARS-CoV-2 vaccines. In rare cases (1.4%) symptoms persisted ≥ 90 days. Question of causality should further be scrutinized in future prospective studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Registration\u003c/strong\u003e: This study was registered at the German Clinical Trials Register (Register-ID: DRKS00031994).\u003c/p\u003e","manuscriptTitle":"CoVacU18-Study: Long-Term Safety of BNT162b2 in Children under 18 Years in Germany","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-10 01:54:24","doi":"10.21203/rs.3.rs-4566186/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c9b659c3-caf7-4249-94ff-adb55cc70c9c","owner":[],"postedDate":"July 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-10T01:54:27+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-10 01:54:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4566186","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4566186","identity":"rs-4566186","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}