Stable fitness during COVID-19: Results of serial testing in a cohort of youth with heart disease.

Background: Little is known about how sport and school restrictions early during the novel coronavirus 2019 (COVID-19) pandemic impacted exercise performance and body composition in youth with heart disease (HD). Methods: A retrospective chart review was performed on all patients with HD who had serial exercise testing and body composition via bioimpedance analysis performed within 12 months before and during the COVID-19 pandemic. Formal activity restriction was noted as present or absent. Analysis was performed with a paired t-test. Results: There were 33 patients (mean age 15.3 ± 3.4 years; 46% male) with serial testing completed (18 electrophysiologic diagnosis, 15 congenital HD). There was an increase in skeletal muscle mass (SMM) (24.1 ± 9.2-25.9 ± 9.1 kg, p < 0.0001), weight (58.7 ± 21.5-63.9 ± 22 kg, p < 0.0001), and body fat percentage (22.7 ± 9.4-24.7 ± 10.4%, p = 0.04). The results were similar when stratified by age <18 years old (n = 27) or by sex (male 16, female 17), consistent with typical pubertal changes in this predominantly adolescent population. Absolute peak VO2 increased, but this was due to somatic growth and aging as evidenced by no change in % of predicted peak VO2. There remained no difference in predicted peak VO2 when excluding patients with pre-existing activity restrictions (n = 12). Review of similar serial testing in 65 patients in the 3 years before the pandemic demonstrated equivalent findings. Conclusions: The COVID-19 pandemic and related lifestyle changes do not appear to have had substantial negative impacts on aerobic fitness or body composition in children and young adults with HD.

Examination of Adverse Reactions After COVID-19 Vaccination Among Patients With a History of Multisystem Inflammatory Syndrome in Children.

Importance: Data 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. Objective: To describe adverse reactions following COVID-19 vaccination in patients with a history of MIS-C. Design, Setting, and Participants: In 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. Exposures: COVID-19 vaccination after MIS-C diagnosis. Main Outcomes and Measures: The 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. Results: Of 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 Relevance: In 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.

Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021.

Importance: Vaccination against COVID-19 provides clear public health benefits, but vaccination also carries potential risks. The risks and outcomes of myocarditis after COVID-19 vaccination are unclear. Objective: To describe reports of myocarditis and the reporting rates after mRNA-based COVID-19 vaccination in the US. Design, Setting, and Participants: Descriptive study of reports of myocarditis to the Vaccine Adverse Event Reporting System (VAERS) that occurred after mRNA-based COVID-19 vaccine administration between December 2020 and August 2021 in 192 405 448 individuals older than 12 years of age in the US; data were processed by VAERS as of September 30, 2021. Exposures: Vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna). Main Outcomes and Measures: Reports of myocarditis to VAERS were adjudicated and summarized for all age groups. Crude reporting rates were calculated across age and sex strata. Expected rates of myocarditis by age and sex were calculated using 2017-2019 claims data. For persons younger than 30 years of age, medical record reviews and clinician interviews were conducted to describe clinical presentation, diagnostic test results, treatment, and early outcomes. Results: Among 192 405 448 persons receiving a total of 354 100 845 mRNA-based COVID-19 vaccines during the study period, there were 1991 reports of myocarditis to VAERS and 1626 of these reports met the case definition of myocarditis. Of those with myocarditis, the median age was 21 years (IQR, 16-31 years) and the median time to symptom onset was 2 days (IQR, 1-3 days). Males comprised 82% of the myocarditis cases for whom sex was reported. The crude reporting rates for cases of myocarditis within 7 days after COVID-19 vaccination exceeded the expected rates of myocarditis across multiple age and sex strata. The rates of myocarditis were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). There were 826 cases of myocarditis among those younger than 30 years of age who had detailed clinical information available; of these cases, 792 of 809 (98%) had elevated troponin levels, 569 of 794 (72%) had abnormal electrocardiogram results, and 223 of 312 (72%) had abnormal cardiac magnetic resonance imaging results. Approximately 96% of persons (784/813) were hospitalized and 87% (577/661) of these had resolution of presenting symptoms by hospital discharge. The most common treatment was nonsteroidal anti-inflammatory drugs (589/676; 87%). Conclusions and Relevance: Based on passive surveillance reporting in the US, the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata and was highest after the second vaccination dose in adolescent males and young men. This risk should be considered in the context of the benefits of COVID-19 vaccination.

The low incidence of clinically significant heart disease in school-age children following COVID-19. / Baja incidencia de cardiopatía clínicamente significativa en niños en edad escolar tras padecer COVID-19.

The burden of clinically-apparent cardiac injury secondary to coronavirus disease 2019 (COVID-19) in school-age children is unclear. Over 12 months at a large academic pediatric hospital in the Midwestern portion of the United States, there were 1481 COVID-19 positive non-hospitalized otherwise healthy schoolaged children with 195 having cardiac testing performed. While incidental findings occurred, no definitive COVID-19 related cardiac pathology was discovered. Additionally, only ~3% of children had acute cardiac symptoms necessitating evaluation by pediatric cardiology. School-age children who were not hospitalized for COVID-19 have a very low risk of having clinically significant cardiac damage and are more likely to discover incidental findings.

No es clara la carga de morbimortalidad de la lesión cardíaca clínicamente evidente secundaria a la enfermedad por coronavirus de 2019 (COVID-19) en los niños en edad escolar. A lo largo de 12 meses, en un importante hospital pediátrico académico en la región del medio oeste de Estados Unidos, hubo 1481 casos de COVID-19 sin hospitalización en niños en edad escolar por lo demás sanos, en quienes se hicieron 195 pruebas cardíacas. Si bien aparecieron hallazgos fortuitos, no se descubrió ninguna patología cardíaca relacionada con la COVID-19. Además, ~3 % de los niños solamente tuvieron síntomas cardíacos agudos que requirieron una evaluación por el área de cardiología pediátrica. Los niños que no fueron hospitalizados por COVID-19 tienen un riesgo muy bajo de desarrollar daño cardíaco clínicamente significativo y son más propensos a presentar hallazgos fortuitos.

Inflammatory biomarkers in COVID-19-associated multisystem inflammatory syndrome in children, Kawasaki disease, and macrophage activation syndrome: a cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening hyperinflammatory syndrome that occurs after primary SARS-CoV-2 infection. The pathogenesis of MIS-C remains undefined, and whether specific inflammatory biomarker patterns can distinguish MIS-C from other hyperinflammatory syndromes, including Kawasaki disease and macrophage activation syndrome (MAS), is unknown. Therefore, we aimed to investigate whether inflammatory biomarkers could be used to distinguish between these conditions. METHODS: We studied a prospective cohort of patients with MIS-C and Kawasaki disease and an established cohort of patients with new-onset systemic juvenile idiopathic arthritis (JIA) and MAS associated with systemic JIA (JIA-MAS), diagnosed according to established guidelines. The study was done at Cincinnati Children's Hospital Medical Center (Cincinnati, OH, USA). Clinical and laboratory features as well as S100A8/A9, S100A12, interleukin (IL)-18, chemokine (C-X-C motif) ligand 9 (CXCL9), and IL-6 concentrations were assessed by ELISA and compared using parametric and non-parametric tests and receiver operating characteristic curve analysis. FINDINGS: Between April 30, 2019, and Dec 14, 2020, we enrolled 19 patients with MIS-C (median age 9·0 years [IQR 4·5-15·0]; eight [42%] girls and 11 [58%] boys) and nine patients with Kawasaki disease (median age 2·0 years [2·0-4·0]); seven [78%] girls and two [22%] boys). Patients with MIS-C and Kawasaki disease had similar S100 proteins and IL-18 concentrations but patients with MIS-C were distinguished by significantly higher median concentrations of the IFNγ-induced CXCL9 (1730 pg/mL [IQR 604-6300] vs 278 pg/mL [54-477]; p=0·038). Stratifying patients with MIS-C by CXCL9 concentrations (high vs low) revealed differential severity of clinical and laboratory presentation. Compared with patients with MIS-C and low CXCL9 concentrations, more patients with high CXCL9 concentrations had acute kidney injury (six [60%] of ten vs none [0%] of five), altered mental status (four [40%] of ten vs none [0%] of five), shock (nine [90%] of ten vs two [40%] of five), and myocardial dysfunction (five [50%] of ten vs one [20%] of five); these patients also had higher concentrations of systemic inflammatory markers and increased severity of cytopenia and coagulopathy. By contrast, patients with MIS-C and low CXCL9 concentrations resembled patients with Kawasaki disease, including the frequency of coronary involvement. Elevated concentrations of S100A8/A9, S100A12, and IL-18 were also useful in distinguishing systemic JIA from Kawasaki disease with high sensitivity and specificity. INTERPRETATION: Our findings show MIS-C is distinguishable from Kawasaki disease primarily by elevated CXCL9 concentrations. The stratification of patients with MIS-C by high or low CXCL9 concentrations provides support for MAS-like pathophysiology in patients with severe MIS-C, suggesting new approaches for diagnosis and management. FUNDING: Cincinnati Children's Research Foundation, National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health, the Deutsche Forschungsgemeinschaft, and The Jellin Family Foundation.

Review of Cardiac Involvement in Multisystem Inflammatory Syndrome in Children.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with substantial cardiovascular implications. Although infection with SARS-CoV-2 is usually mild in children, some children later develop a severe inflammatory disease that can have manifestations similar to toxic shock syndrome or Kawasaki disease. This syndrome has been defined by the US Centers for Disease Control and Prevention as multisystem inflammatory syndrome in children. Although the prevalence is unknown, >600 cases have been reported in the literature. Multisystem inflammatory syndrome in children appears to be more common in Black and Hispanic children in the United States. Multisystem inflammatory syndrome in children typically occurs a few weeks after acute infection and the putative etiology is a dysregulated inflammatory response to SARS-CoV-2 infection. Persistent fever and gastrointestinal symptoms are the most common symptoms. Cardiac manifestations are common, including ventricular dysfunction, coronary artery dilation and aneurysms, arrhythmia, and conduction abnormalities. Severe cases can present as vasodilatory or cardiogenic shock requiring fluid resuscitation, inotropic support, and in the most severe cases, mechanical ventilation and extracorporeal membrane oxygenation. Empirical treatments have aimed at reversing the inflammatory response using immunomodulatory medications. Intravenous immunoglobulin, steroids, and other immunomodulatory agents have been used frequently. Most patients recover within days to a couple of weeks and mortality is rare, although the medium- and long-term sequelae, particularly cardiovascular complications, are not yet known. This review describes the published data on multisystem inflammatory syndrome in children, focusing on cardiac complications, and provides clinical considerations for cardiac evaluation and follow-up.