ImportanceData are limited regarding adverse reactions after COVID-19 vaccination in patients with a history of multisystem inflammatory syndrome in children (MIS-C). The lack of vaccine safety data in this unique population may cause hesitancy and concern for many families and health care professionals.ObjectiveTo describe adverse reactions following COVID-19 vaccination in patients with a history of MIS-C.Design, Setting, and ParticipantsIn this multicenter cross-sectional study including 22 North American centers participating in a National Heart, Lung, and Blood Institute, National Institutes of Health–sponsored study, Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children (MUSIC), patients with a prior diagnosis of MIS-C who were eligible for COVID-19 vaccination (age ≥5 years; ≥90 days after MIS-C diagnosis) were surveyed between December 13, 2021, and February 18, 2022, regarding COVID-19 vaccination status and adverse reactions.ExposuresCOVID-19 vaccination after MIS-C diagnosis.Main Outcomes and MeasuresThe main outcome was adverse reactions following COVID-19 vaccination. Comparisons were made using the Wilcoxon rank sum test for continuous variables and the χ2 or Fisher exact test for categorical variables.ResultsOf 385 vaccine-eligible patients who were surveyed, 185 (48.1%) received at least 1 vaccine dose; 136 of the vaccinated patients (73.5%) were male, and the median age was 12.2 years (IQR, 9.5-14.7 years). Among vaccinated patients, 1 (0.5%) identified as American Indian/Alaska Native, non-Hispanic; 9 (4.9%) as Asian, non-Hispanic; 45 (24.3%) as Black, non-Hispanic; 59 (31.9%) as Hispanic or Latino; 53 (28.6%) as White, non-Hispanic; 2 (1.1%) as multiracial, non-Hispanic; and 2 (1.1%) as other, non-Hispanic; 14 (7.6%) had unknown or undeclared race and ethnicity. The median time from MIS-C diagnosis to first vaccine dose was 9.0 months (IQR, 5.1-11.9 months); 31 patients (16.8%) received 1 dose, 142 (76.8%) received 2 doses, and 12 (6.5%) received 3 doses. Almost all patients received the BNT162b2 vaccine (347 of 351 vaccine doses [98.9%]). Minor adverse reactions were observed in 90 patients (48.6%) and were most often arm soreness (62 patients [33.5%]) and/or fatigue (32 [17.3%]). In 32 patients (17.3%), adverse reactions were treated with medications, most commonly acetaminophen (21 patients [11.4%]) or ibuprofen (11 [5.9%]). Four patients (2.2%) sought medical evaluation, but none required testing or hospitalization. There were no patients with any serious adverse events, including myocarditis or recurrence of MIS-C.Conclusions and RelevanceIn this cross-sectional study of patients with a history of MIS-C, no serious adverse events were reported after COVID-19 vaccination. These findings suggest that the safety profile of COVID-19 vaccination administered at least 90 days following MIS-C diagnosis appears to be similar to that in the general population.

ImportanceKawasaki disease (KD) symptoms significantly overlap with multisystem inflammatory syndrome in children due to COVID-19. Patients with KD may be at risk for adverse outcomes from exposure to SARS-CoV-2 infection or vaccination.ObjectiveTo describe the outcomes of patients with KD to SARS-CoV-2 infection or vaccination.Design, Setting, and ParticipantsThis case series evaluated 2 cohorts using an existing KD database and reviewed individual electronic medical records for the period spanning January 1, 2020, through January 31, 2022, via electronic medical records that include Washington state immunization records. Vaccine cohort inclusion criteria consisted of being 21 years or younger at immunization and receiving 1 or more BNT162b2 (Pfizer-BioNTech) or messenger RNA (mRNA)–1273 (Moderna) vaccine doses. The COVID-19 cohort included patients 21 years or younger with positive polymerase chain reaction or nuclear capsid IgG findings for SARS-CoV-2. Participants included 826 patients from a preexisting KD database. One hundred fifty-three patients received at least 1 BNT162b2 or mRNA-1273 vaccine dose and were included in the mRNA vaccine cohort. Thirty-seven patients had positive test results for SARS-CoV-2 and were included in the COVID-19 cohort.ExposuresSARS-CoV-2 vaccination and/or infection.Main Outcomes and MeasuresAdverse events after mRNA vaccination and/or COVID-19, including clinician visits, emergency department encounters, or hospitalizations.ResultsAmong the 153 patients included in the mRNA vaccination cohort (mean [SD] age, 13.0 [4.3] years; 94 male [61.4%]), the BNT162b2 vaccine was provided for 143 (93.5%), and the remaining 10 (6.5%) received mRNA-1273 or a combination of both. Among patients in the vaccine cohort, 129 (84.3%) were fully vaccinated or received a third-dose booster. No clinically severe adverse events occurred, and there were no reports of vaccine-related hospitalizations or outpatient visits. The COVID-19 cohort included 37 patients (mean [SD] age, 11.0 [5.5] years; 22 male [59.5%]). No patients required hospitalization due to COVID-19. The most common symptoms included low-grade fever, fatigue, cough, and myalgia with resolution within a few days. Two patients, aged 9 and 19 years, had extended cough and fatigue for 3 to 4 weeks. One patient developed COVID-19 within 6 weeks of receiving intravenous immunoglobulin for KD.Conclusions and RelevanceThese findings suggest that the mRNA vaccines may be safe and COVID-19 may not be severe for patients with a history of KD.

Kawasaki disease is a systemic vasculitis, especially of the coronary arteries, affecting children. Despite extensive research, much is still unknown about the principal driver behind the amplified inflammatory response. We propose mitochondria may play a critical role. Mitochondria serve as a central hub, influencing energy generation, cell proliferation, and bioenergetics. Regulation of these biological processes, however, comes at a price. Release of mitochondrial DNA into the cytoplasm acts as damage-associated molecular patterns, initiating the development of inflammation. As a source of reactive oxygen species, they facilitate activation of the NLRP3 inflammasome. Kawasaki disease involves many of these inflammatory pathways. Progressive mitochondrial dysfunction alters the activity of immune cells and may play a role in the pathogenesis of Kawasaki disease. Because they contain their own genome, mitochondria are susceptible to mutation which can propagate their dysfunction and immunostimulatory potential. Population-specific variants in mitochondrial DNA have also been linked to racial disparities in disease risk and treatment response. Our objective is to critically examine the current literature of mitochondria’s role in coordinating proinflammatory signaling pathways, focusing on potential mitochondrial dysfunction in Kawasaki disease. No association between impaired mitochondrial function and Kawasaki disease exists, but we suggest a relationship between the two. We hypothesize a framework of mitochondrial determinants that may contribute to ethnic/racial disparities in the progression of Kawasaki disease.

Introduction: Kawasaki Disease (KD) leads as a cause of acquired cardiovascular disease among children in developed countries. Around~20% of patients are refractory to high-dose intravenous immunoglobulin (IVIG), the standard treatment, and are at high risk of developing coronary artery aneurysms. Hypothesis: Whole genome sequencing (WGS) will identify specific predictors of non-response and inform the mechanism of IVIG action. Methods: KD patients were diagnosed by the American Heart Association and the American Academy of Pediatrics (AHA/AAP) criteria and treated by AHA guidelines. IVIG refractoriness was defined by persistent or recurrent fever (>38C)>36 hours after completing infusion. We performed a case-control study with WGS on DNA from saliva or blood from 107 responders versus 103 non-responders. After processing informatics using the pipeline of Genome Analysis Toolkit (GATK), additive genetic models were assessed for all common variants using logistic regression. We adjusted for age, gender, and race based on principal components. We also conducted SNP-set (Sequence) Kernel Association Test (SKAT) with common and rare variants in the gene regions with the most statistically significant SNP results. Results: Average sequencing depth was 30x and with a total of 34,548,910 variants. While SNPs in genes previously indicated in the IVIG pathway were confirmed, multiple novel SNPs in various gene regions were also statistically significant (often p< 10-6; Figure-Manhattan plot). SKAT analysis suggested joint effects of multiple SNPs in individual gene regions. Conclusions: We confirmed SNPs in genes from previous reports and identified multiple novel ones, indicating plausible previous unsuspected IVIG mechanisms pathways. Potentially, functional disruption of these genes could lead to non-response. Further, a panel of these SNPs can be a prognostic tool for identifying at-risk KD patients that require therapy intensification.

Introduction: Kawasaki disease (KD) and multisystem inflammatory syndrome in children from COVID-19 infections share overlapping symptoms, suggesting KD patients may be at risk for adverse outcomes from exposure to SARS-CoV-2 mRNA vaccine or infection. Through retrospective review of clinical outcome data, we determined tolerance of KD patients to SARS-CoV-2 antigen exposure. Methods: We evaluated two cohorts using an existing KD database of 826 patients and reviewed individual electronic medical records for the period spanning January 2020 through Jan 2022 via Epic Care Everywhere which includes Washington State immunization records. Vaccine cohort inclusion criteria were (1) age &lt 21 years at immunization and (2) received one or more Pfizer-BioNTech or Moderna vaccine doses. The COVID-19 infection cohort included (1) age &lt 21 years and (2) positive SARS-CoV-2 PCR or nuclear capsid IgG. Results: The vaccine cohort contained 153 patients with vaccine distribution by age subgroups shown in Figure 1. Pfizer-BioNTech vaccine was provided for 93.5% and the remaining received Moderna or a combination. 84.3% were fully vaccinated or received a third-dose booster. No clinically severe adverse events occurred including no vaccine-related hospitalizations or outpatient visits. The COVID-19 infection cohort included thirty-seven patients. No patients required hospitalization. The most common symptoms included low grade fever, fatigue, cough, and myalgia with resolution within a few days. Two patients, 9 and 19 years, had extended cough and fatigue for 3-4 weeks. One patient developed COVID-19 within 6 weeks of receiving IVIG for KD. Conclusions: COVID-19 infections and vaccinations are well tolerated in patients with preceding KD. No severe complications occurred in either cohort with only two patients exhibiting prolonged mild symptoms from COVID-19. This study provides assurance regarding vaccine safety and COVID-19 severity for parents of children with KD.