key: cord-0723907-n4kmijxp authors: Hoste, Levi; Soriano-Arandes, Antoni; Buddingh, Emilie Pauline; Whittaker, Elizabeth; Belot, Alexandre; Ulloa-Gutierrez, Rolando; Olbrich, Peter; Haerynck, Filomeen title: SARS-CoV-2 vaccination in children with a history of MIS-C: an international survey date: 2022-05-19 journal: J Pediatr DOI: 10.1016/j.jpeds.2022.05.028 sha: 1723c7f4a43e442e051e5a040fb374d7a824b8be doc_id: 723907 cord_uid: n4kmijxp The optimal SARS-CoV-2 vaccine strategy for patients with a history of MIS-C is unclear. We performed an international survey (32 countries) and found substantial variations in vaccine policies. Respondents did not report relapses of MIS-C or other severe inflammatory side effects after SARS-CoV-2 vaccination in 273 patients with a history of MIS-C. underlying the pathophysiology of MIS-C. to date, limited data are available on children receiving SARS-CoV-2 vaccination after MIS-C. We performed an international survey among healthcare professionals to assess experience with tolerability of SARS-CoV-2 vaccine in children with a history of MIS-C. MethodsOur cross-sectional electronic survey (Appendix; available at www.jpeds.com)was comprised of 24 questions, covering vaccination policies used for children with previous MIS-C (local, regional and/or national guidelines); number of children with a history of MIS-C who were or were not (yet) vaccinated against SARS-CoV-2; and identification of uncommon adverse events, codified as possible, probable, or certain, occurring after SARS-CoV-2 vaccination in these children. Respondents were asked to specify if the entered cases were counted accurately (e.g. registered as cases) or as estimated numbers. The survey link was distributed globally through personal communication by the authors and through e-mail invitations by multiple professional (inter)national societies of pediatrics, infectious diseases, intensive care medicine, inborn errors of immunity, Kawasaki disease/MIS-C networks, and clinical trials networks. Participants also were asked to distribute the survey invitation to other colleagues involved in MIS-C care. The professional background of respondents was evaluated to confirm relevant roles in MIS-C patient care and/or policymaking. IP addresses were verified to ensure the uniqueness of each participant. Possible overlapping data (e.g. national data that included regional counts) were excluded after personal communication with the involved respondents. Given the study design, overall survey response rates and subsequently any comparisons between survey respondents with non-respondents could not be performed. On an individual patient level, no identifiable information was collected. Data were collected from November 1, 2021 to December 15, 2021. healthcare professionals (n =132) involved in the care of patients with MIS-C initiated the survey. After excluding incomplete entries, we collected complete data from 83 health care professionals, from 32 different countries (Figure 1 ). Most respondents were clinicians (79/83) and/or clinical researchers (21/83). Most children with prior MIS-C were vaccinated in the same locations as healthy children according to local health authority guidelines such as vaccination centers or schools (n=45 respondents), hospitals without admission (n=3 from India, Italy and Turkey) or hospitals with admission (n=13 from Belgium, South Korea, Colombia, Indonesia, Spain, Turkey, India, Italy, USA). Only one respondent from Italy declared that vaccination in a hospital without admission was a specific procedure for MIS-C not applying to healthy children. Most respondents (for 54 of 65 entries without contraindication for vaccination) could not provide specific data on mild or moderate AE, either because there was lack of formal registration and/or that respondents were not at all confronted with these specific AE in patients. Of registered data, mild or moderate AE were reported to a variable extent including both localized reactions (swelling, redness, pain) and systemic responses (fever, chills, nausea, fatigue, headache, lymphadenopathy). As such, frequencies of AEs for individual entries ranged from 0 to 100% of patients, although importantly, all mild or moderate AEs disappeared after 1-3 days without requiring specific interventions. One 13-year-old male was reported with acute-onset facial nerve palsy (Bell palsy), one week after his second BNT162b2 (Pfizer-BioNTech) vaccine. He was hospitalized and given methylprednisolone (40mg/day) and recovered without sequelae. No other severe AE was reported by the participants. Importantly, no MIS-C relapse or any other inflammatory conditions were reported after vaccination. The survey documents heterogeneity of vaccine policy as well as limited data on vaccination after recovery from MIS-C Our data suggest that vaccine recommendations or their understanding or both in the context of MIS-C not only differ between continents and healthcare systems, but also within countries. Potential harms and J o u r n a l P r e -p r o o f benefits of SARS-CoV-2 vaccination in children with a history of MIS-C may be weighted differently in each setting. Individual choices or concerns regarding vaccine safety also might exist. Although SARS-CoV-2 vaccination was not contraindicated in patients according to CDC guidelines, we observed a heterogeneous advice within respondents from the USA [29] Although in most countries adverse events of vaccines and drugs are registered centrally by healthcare agencies, the rarity of MIS-C and the absence of registries documenting follow up of vaccination episodes in affected patients leads to a lack of specific knowledge regarding tolerability of SARS-CoV-2 vaccination in these children. we found that in most regions around the world, MIS-C is not considered a contra-indication for SARS-CoV-2 vaccination. In addition, respondents stated that 273 patients effectively received at least one dose of SARS-CoV-2 vaccine after MIS-C. There was no overt experience of increased frequency or severity of AE and no case of MIS-C relapse or other inflammatory conditions after vaccination Our observations are consistent with the overall good safety profile of SARS-CoV-2 vaccines in healthy children. SARS-CoV-2 vaccination is associated with a reduced risk of development of MIS-C after infection [30, 31] . It should be noted that Bell palsy was reported as a severe AE in one patient [32] , and generally is reversible [33] . Administration of a SARS-CoV-2 vaccine after MIS-C was assessed by 20% of participants as contraindicated Furthermore, a substantial number of patients with MIS-C, even if already eligible for vaccination (30% of the cohort), had not been vaccinated or were possibly vaccinated, and 60.4% were not). In addition, some respondents declared to propose longer intervals between MIS-C and vaccination or different dosing schedules than for previously healthy children, potentially exposing patients with MIS-C to a higher risk of reinfection. More detailed information on safety of delayed vaccination or one-versus two-dose vaccination will be of value in order to define the optimal vaccine strategy for this specific group of patients. it will be of interest to document whether occurrence of MIS-C is limited to primary exposure to SARS-CoV-2 or if MIS-C, and with what frequency, following re-infection [34] . This analysis is limited by the temporary nature of its data, especially in the midst of an evolving pandemic and vaccine policies. When this survey was initiated, SARS-CoV-2 vaccines were not yet universally accessible for children 5-11 years of age, representing a substantial proportion of MIS-C patients [4] . The J o u r n a l P r e -p r o o f 8 systematic and prospective collection of additional safety data on younger MIS-C patients is important to either support or adjust conclusions beyond the current context of predominantly adolescent MIS-C patients receiving the BNT162b2 (Pfizer-BioNTech) vaccine. A major limitation of the study design is that in only 273 cases vaccine administration has been confirmed, with a potential bias related to recall or notification of adverse events. It seems unlikely, however, that attending physicians or healthcare providers would not have been notified of important inflammatory complications or MIS-C relapses. We did not collect individual data on patients, so information on the demography of those vaccinated, the number of doses administered or the interval between MIS-C and SARS-CoV-2 vaccination was not documented. Finally, data represent a convenience sample supplied by numerous professionals involved with MIS-C patient care worldwide who chose to participate and should be interpreted as such. 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Multisystemic inflammatory syndrome following COVID-19 mRNA vaccine in children: a national post-authorization pharmacovigilance study Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Approved or Authorized in the United States Multisystem Inflammatory Syndrome in Children by COVID-19 Vaccination Status of Adolescents in France Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA Vaccination Against Multisystem Inflammatory Syndrome in Children Among Persons Aged 12-18 Years -United States Bell's palsy following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines: a case series and nested casecontrol study Bell's palsy: aetiology, clinical features and multidisciplinary care Reinfection With Severe Acute Respiratory Syndrome Coronavirus 2 Without Recurrence of Multisystem Inflammatory Syndrome in Children The authors declare no competing interests. LH, PO and FH conceptualized the study and drafted the survey. LH analyzed and interpreted the data. ASA, EPB, EW, AB and R.U-G had crucial roles in data acquisition and provided scientific guidance. PO and FH supervised research methodology, data analysis and interpretation. LH, PO and FH drafted the initial version of the manuscript. All authors revised the manuscript and gave their final approval of the version to be published.The authors wish to express their sincere gratitude to all collaborating partners including Chiara Biazzo for the relevant literature search. MIS-C researchers that provided data for their hospital (network), region or country are listed in the Appendix.