COVID-19 Positive Versus Negative Complete Kawasaki Disease: A Study from the International Kawasaki Disease Registry.

To determine clinical differences for children with complete Kawasaki disease (KD) with and without evidence of preceding SARS-CoV-2 infection. From January 2020, contemporaneous patients with complete KD criteria were classified as either SARS-CoV-2 positive (KDCOVID+; confirmed household exposure, positive PCR and/or serology) or SARS-CoV-2 negative (KDCOVID-; negative testing and no exposure) and compared. Of 744 patients in the International Kawasaki Disease Registry, 52 were KDCOVID- and 61 were KDCOVID+. KDCOVID+ patients were older (median 5.5 vs. 3.7 years; p < 0.001), and all additionally met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C). They were more likely to have abdominal pain (60% vs. 35%; p = 0.008) and headache (38% vs. 10%; p < 0.001) and had significantly higher CRP, troponin, and BUN/creatinine, and lower hemoglobin, platelets, and lymphocytes. KDCOVID+ patients were more likely to have shock (41% vs. 6%; p < 0.001), ICU admission (62% vs. 10%; p < 0.001), lower left ventricular ejection fraction (mean lowest LVEF 53% vs. 60%; p < 0.001), and to have received inotropic support (60% vs. 10%; p < 0.001). Both groups received IVIG (2 doses in 22% vs. 18%; p = 0.63), but KDCOVID+ were more likely to have received steroids (85% vs. 35%; p < 0.001) and anakinra (60% vs. 10%; p = 0.002). KDCOVID- patients were more likely to have medium/large coronary artery aneurysms (CAA, 12% vs. 0%; p = 0.01). KDCOVID+ patients differ from KDCOVID-, have more severe disease, and greater evidence of myocardial involvement and cardiovascular dysfunction rather than CAA. These patients may be a distinct KD phenotype in the presence of a prevalent specific trigger.

Cardiac Biomarkers Aid in Differentiation of Kawasaki Disease from Multisystem Inflammatory Syndrome in Children Associated with COVID-19.

Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.

EKG Abnormalities in a Youth Athlete Following COVID-19: It's Not Always Myocarditis!

COVID-19 associated myocarditis following mild infections is rare while incidental findings may be more common. A young athlete fully recovered from a mild COVID-19 infection presented with inferolateral T-wave inversions and left ventricular hypertrophy on imaging. Exercise testing aided in correctly diagnosing the patient with masked systolic hypertension.

Incorporation of the CardioMEMS™ System During an Exercise Physiology Test in a Pediatric Congenital Heart Disease Patient Contributing to Medical Decision-Making.

Exercise testing among the pediatric congenital heart disease population continues to transform and expand the way patients are evaluated and managed. We describe a case where a stress echocardiogram was performed while successfully collecting data from a previously implanted CardioMEMS™ HF system which helped guide decision-making.

Esophageal acid burden in reflux patients with normal endoscopy: Does esophageal peristalsis matter?

BACKGROUND: A majority of patients with gastroesophageal reflux disease (GERD) have normal endoscopy. We aimed to investigate whether esophageal primary and secondary peristalsis influence esophageal reflux parameters in patients with normal endoscopy. METHODS: We enrolled consecutive patients with typical reflux symptoms and normal endoscopy. All patients underwent High resolution manometry (HRM) and 24-h impedance-pH studies off therapy. During HRM, secondary peristalsis was evaluated using ten 20-mL rapid air infusions into the esophagus, while primary peristalsis was evaluated using ten 5-mL water swallows. RESULTS: A total of 43 patients completed the study; 13 patients had normal motility, 20 had ineffective esophageal motility (IEM), and 10 had absent contractility. Acid exposure time (AET) (total, supine, and upright) was significantly higher in those with absent primary peristalsis (absent contractility) compared to normal motility (P = 0.001; 0.01; 0.007) and IEM (P = 0.002; 0.02; 0.03). Supine AET was significantly higher in patients without secondary peristalsis compared to those with secondary peristalsis (P = 0.04). CONCLUSION: In the setting of normal endoscopy, acid reflux burden is more profound in patients with absent primary peristalsis, as well as in patients lacking a secondary peristaltic response to esophageal air distension.

Effects of codeine on esophageal peristalsis in humans using high resolution manometry.

BACKGROUND AND AIM: Opioid receptors agonists have been demonstrated to impair lower esophageal sphincter (LES) relaxation and induce spastic esophageal dysmotility, but little was known for their impact on distension-induced secondary peristalsis. The aim of the study was to investigate the hypothesis whether acute administration of codeine can influence physiological characteristics of primary and secondary peristalsis in healthy adults. METHODS: Eighteen healthy volunteers (13 men, mean age 27.5 years, aged 20-43 years) underwent high resolution manometry (HRM) with a catheter containing an injection port in mid-esophagus. Secondary peristalsis was performed with 10 and 20 mL rapid air injections. Two different sessions including acute administration of codeine (60 mg) or the placebo were randomly performed. RESULTS: Codeine significantly increased 4-s integrated relaxation pressure (IRP-4s) (P = 0.003) and shortened distal latency (DL) (P = 0.003) of primary peristalsis. The IRP-4s of secondary peristalsis was also significantly higher after codeine than the placebo during air injections with 10 mL (P = 0.048) and 20 mL (P = 0.047). Codeine significantly increased the frequency of secondary peristalsis during air injections with 10 mL than the placebo (P = 0.007), but not for air injection with 20 mL (P = 0.305). CONCLUSIONS: In addition to impair LES relaxation and reduce distal latency of primary peristalsis, codeine impairs LES relaxation of secondary peristalsis and increases secondary peristaltic frequency. Our study supports the notion in human esophagus that the impact of opioids on peristaltic physiology appears to be present in both primary and secondary peristalsis.

Effect of prucalopride on sildenafil-induced inhibition of esophageal peristalsis in healthy adults.

BACKGROUND AND AIM: Prucalopride, a high-affinity 5-hydroxytryptamine 4 receptor agonist, promotes esophageal peristalsis, while phosphodiesterase type 5 inhibitor sildenafil inhibits esophageal peristalsis. The present study was aimed to evaluate whether prucalopride would augment esophageal peristalsis subsequent to the application of sildenafil. METHODS: Seventeen healthy adults underwent high-resolution manometry by a catheter with one injection port located in the mid-esophagus. Secondary peristalsis was assessed by rapid air injections after water swallows. Two sessions were randomly performed including acute administration of sildenafil 50 mg after pretreatment with prucalopride or the placebo. RESULTS: The frequency of primary peristalsis subsequent to the administration of sildenafil was significantly increased by prucalopride (P = 0.02). Prucalopride also significantly increased distal contractile integral of primary peristalsis subsequent to the administration of sildenafil (P = 0.03). No difference in the frequency of secondary peristalsis subsequent to the administration of sildenafil for air injects of 10 mL (P = 0.14) or 20 mL (P = 0.21) was found between prucalopride and placebo. Prucalopride did not change distal contractile integral of secondary peristalsis subsequent to the administration of sildenafil for air injections of 10 mL (P = 0.09) or 20 mL (P = 0.12). CONCLUSIONS: Prucalopride modulates sildenafil-induced inhibition of primary peristalsis by increasing its effectiveness and peristaltic wave amplitude. Our findings suggest that activation of 5-hydroxytryptamine 4 receptors plays a role in mediating sildenafil-induced inhibition of esophageal primary peristalsis rather than secondary peristalsis.

Recanalization of an atretic intramural left main coronary artery after bypass surgery in a pediatric patient with anomalous aortic origin of the left main coronary artery arising from the right sinus of Valsalva.

We report a pediatric patient with nonatherosclerotic chronic total occlusion (CTO) of the left main coronary artery (LMCA) leading to complete LMCA atresia which was successfully recanalized via retrograde techniques through a previous internal mammary bypass graft. After the CTO was treated, the artery was found to be anomalous off the right cusp with an intramural coarse and slit-like orifice. The patient's ischemic symptoms resolved after Percutaneous Coronary Intervention (PCI), and she has continued to do well.

Institutional experience of healthy pediatric patients presenting with atrial fibrillation who had an electrophysiology study.

INTRODUCTION: Atrial fibrillation (AF) is a very common tachyarrhythmia with increasing prevalence with age, but uncommon in the pediatric population. Understanding that AF increases comorbidities make the need for investigation and potential elimination of alternate etiologies in pediatric AF patients critical. The objective of this study was to review our institutional data and compare our findings with previously documented adult AF risk factors to pediatric patients while also identifying which patients had alternate electrophysiology diagnoses amenable to transcatheter ablation. METHODS: A retrospective chart review was performed identifying AF patients who were less than 21 years old, had no significant congenital cardiovascular anomalies, a documented episode of AF on electrocardiogram and underwent invasive electrophysiology study (EPS). RESULTS: Nineteen patients were identified over a 9-year period of time finding a male predominance (74%), the average age of 14.95 ± 4.17 years, the average weight of 78.5 ± 31.4 kg, and average body mass index of 26.8 ± 6.87 kg/m2 . Preprocedural left atrial volumes made on echocardiograms demonstrated a mean of 33.96 ± 16.35 mL/m2 (Z-scores -0.81 ± 1.50), indicating no dilation. Five of nineteen patients (26%) had additional electrophysiologic diagnoses during EPS, including atrioventricular reentrant tachycardia (n = 2, 10%) and atrioventricular nodal reentrant tachycardia (n = 3, 16%). Four patients underwent successful ablation with no documented or clinical AF recurrence. CONCLUSIONS: Adult risk factors of male predominance and obesity were seen in pediatric AF patients, while left atrial enlargement was not. Twenty-one percent of the pediatric AF patients who had additional electrophysiologic substrates and successful ablations resulted in no further clinical episodes of AF. This suggests that pediatric patients presenting with AF might benefit from an EPS as part of a complete evaluation.

Impact of concomitant dyspepsia and irritable bowel syndrome on symptom burden in patients with gastroesophageal reflux disease.

BACKGROUND: Patients with gastroesophageal reflux disease (GERD) frequently report symptoms like dyspepsia or/and irritable bowel syndrome (IBS). The aim of the study was to investigate the impact of symptom overlap on GERD symptom burden. We also investigate whether GERD overlapping dyspepsia or/and IBS would have different clinical and psychological features as compared with GERD alone. METHODS: A total of 2752 subjects were screened from a health check-up population. We compared the clinical and psychological factors among subjects with GERD alone and with overlap of two or all three diseases. All participants underwent an evaluation with questionnaires including Reflux Disease Questionnaire score, Pittsburgh Sleep Quality Index, Taiwanese Depression Questionnaire, and State-Trait Anxiety Inventory before receiving endoscopic exam. RESULTS: Among the GERD population, we identified 26 with IBS (GERD-IBS), 60 with dyspepsia (GERD-D), and 25 subjects with overlap of all three conditions (GERD-D-IBS). GERD-D and GERD-D-IBS subjects had more severe GERD symptoms as compared subjects with GERD alone (p < 0.001). Subjects with overlapping dyspepsia or/and IBS showed a significant increase in the severity of depression and poorer sleep quality than subjects with GERD alone. Notably, anxiety scores did not differ significantly between subjects with overlapping diseases and GERD alone. CONCLUSION: Our study demonstrates that disease overlap in GERD population is associated with greater symptom burden, higher depression and poorer sleep quality, but not with anxiety. This study highlights the importance of identifying overlapping conditions as a therapeutic strategy for better management of GERD.

Overexpression of antimicrobial peptides contributes to aging through cytotoxic effects in Drosophila tissues.

The innate immune response tends to become hyperactive and proinflammatory in older organisms. We investigated connections between activity of the immune-related genes and aging using the Drosophila model. A hallmark of Drosophila immunity is the production of antimicrobial peptides (AMP), whose expression is triggered via activation of the Toll and Imd immune pathways and regulated by NF-ĸB-like transcription factors, Dif/Dorsal and Relish. It was previously shown that overexpression of the upstream component of the immune pathways shortens lifespan via activation of the Relish-dependent immune response. Here we show that direct overexpression of the Relish target AMP genes broadly at high levels or in the fat body induced apoptosis, elicited depolarization of the mitochondria and significantly shortened lifespan. Underexpression of Relish in the fat body beginning in the second half of lifespan prevented overactivation of AMPs and extended longevity. Unlike infection-induced responses, the age-related increase in AMPs does not require the upstream recognition/transduction module of the Imd pathway. It does however require downstream elements, including Relish and Ird5, a component of the downstream IKK complex. Together, these results established causal links between high-level production of antimicrobial peptides and longevity.

The role of peroxiredoxin 4 in inflammatory response and aging.

In prior studies, we determined that the moderate overexpression of the Drosophila endoplasmic reticulum (ER)-localized peroxiredoxin (Prx), dPrx4, reduced oxidative damage and conferred beneficial effects on life span, while a high-level expression increased the incidence of tissue-specific apoptosis and dramatically shortened longevity. The detrimental pro-apoptotic and life-shortening effects were attributed to aberrant localization of dPrx4 and the apparent ER stress elicited by dPrx4 overexpression. In addition, the activation of both the NF-κB- and the JAK/STAT-mediated stress responses was detected, although it was not clear whether these served as functional alarm signals. Here we extend these findings to show that the activation of the NF-κB-dependent immunity-related/inflammatory genes, associated with life span shortening effects, is dependent on the activity of a Drosophila NF-κB ortholog, Relish. In the absence of Relish, the pro-inflammatory effects typically elicited by dPrx4 overexpression were not detected. The absence of Relish not only prevented the hyperactivation of the immunity-related genes but also significantly rescued the severe shortening of life span normally observed in dPrx4 overexpressors. The overactivation of the immune/inflammatory responses was also lessened by JAK/STAT signaling. In addition, we found that cellular immune/pro-inflammatory responses provoked by the oxidant paraquat but not bacteria are mediated via dPrx4 activity in the ER, as the upregulation of the immune-related genes was eliminated in flies underexpressing dPrx4, whereas immune responses triggered by bacteria were unaffected. Finally, efforts to reveal critical tissues where dPrx4 modulates longevity showed that broad targeting of dPrx4 to neuronal tissue had strong beneficial effects, while targeting expression to the fat body had deleterious effects.

Mitochondrial peroxiredoxins are essential in regulating the relationship between Drosophila immunity and aging.

Previously, we have shown that flies under-expressing the two mitochondrial peroxiredoxins (Prxs), dPrx3 and dPrx5, display increases in tissue-specific apoptosis and dramatically shortened life span, associated with a redox crisis, manifested as changes in GSH:GSSG and accumulation of protein mixed disulfides. To identify specific pathways responsible for the observed biological effects, we performed a transcriptome analysis. Functional clustering revealed a prominent group enriched for immunity-related genes, including a considerable number of NF-kB-dependent antimicrobial peptides (AMP) that are up-regulated in the Prx double mutant. Using qRT-PCR analysis we determined that the age-dependent changes in AMP levels in mutant flies were similar to those observed in controls when scaled to percentage of life span. To further clarify the role of Prx-dependent mitochondrial signaling, we expressed different forms of dPrx5, which unlike the uniquely mitochondrial dPrx3 is found in multiple subcellular compartments, including mitochondrion, nucleus and cytosol. Ectopic expression of dPrx5 in mitochondria but not nucleus or cytosol partially extended longevity under normal or oxidative stress conditions while complete restoration of life span occurred when all three forms of dPrx5 were expressed from the wild type dPrx5 transgene. When dPrx5 was expressed in mitochondria or in all three compartments, it substantially delayed the development of hyperactive immunity while expression of cytosolic or nuclear forms had no effect on the immune phenotype. The data suggest a critical role of mitochondria in development of chronic activation of the immune response triggered by impaired redox control.

Relevance of sleep disturbance to the integrity and characteristics of secondary peristalsis in patients with gastroesophageal reflux disease.

OBJECTIVE: Sleep disturbance is common in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis is important for clearance of the refluxate from the esophagus. We aimed to test the hypothesis whether secondary peristalsis is impaired in GERD patients with sleep disturbance. METHODS: Secondary peristalsis was stimulated with slow and rapid air injections into mid-esophagus in 8 age-matched health controls and 41 patients with GERD. Sleep disturbance was assessed by the Pittsburg Sleep Quality Index (PSQI). Objective sleep measures were assessed by ambulatory actigraphy. RESULTS: The threshold volume for inducing secondary peristalsis during slow air injection was significantly higher in GERD patients with sleep disturbance than healthy controls (14.3 ± 1.2 vs. 8.9 ± 0.5 mL, p < .05). GERD patients with sleep disturbance had higher threshold volume of secondary peristalsis during rapid air injection than GERD patients without sleep disturbance (5.1 ± 0.4 vs. 3.9 ± 0.2 mL, p < .05) and healthy controls (5.1 ± 0.4 vs. 3.6 ± 0.2 mL, p < .05). There was a negative correlation between PSQI score and peristaltic frequency during rapid air injection (r = -.39, p = .01). Secondary peristaltic amplitude during rapid air injection was negatively correlated with wake after sleep onset (r = -.34, p = .04). CONCLUSIONS: Sleep disturbance is associated with secondary peristaltic response to distension-induced esophageal stimulation in patients with GERD. Our study suggests that sleep disturbance per se may adversely influence the effectiveness of esophageal peristalsis and bolus clearance during sleep in patients with GERD.

Sleep disturbance and enhanced esophageal capsaicin sensitivity in patients with gastroesophageal reflux disease.

BACKGROUND AND AIM: Esophageal infusion of capsaicin-containing red pepper sauce induced heartburn symptoms in patients with gastroesophageal reflux disease (GERD). We aimed to test the hypothesis whether sleep disturbance modulates esophageal sensitivity to capsaicin infusion in patients with GERD. METHODS: We enrolled 40 patients with their sleep quality measured by the Pittsburg Sleep Quality Index with > 5 indicating sleep disturbance. Esophageal sensation to capsaicin infusion was documented via measures of lag time to initial heartburn perception, heartburn intensity rating, and sensitivity score by esophageal infusion of capsaicin-containing red pepper sauce. Objective sleep measures were assessed by ambulatory actigraphy. RESULTS: We found 22 patients with sleep disturbance. The patients with sleep disturbance had shorter lag time to initial heartburn perception (P = 0.03) and greater sensory intensity rating (P = 0.02). The sensitivity score for capsaicin infusion was greater in patients with sleep disturbance when compared with those without sleep disturbance (P = 0.04). Actigraphy measures revealed that patients with sleep disturbance also had poor sleep efficiency (P = 0.04), longer average awakening time (P = 0.03), and greater total activity account (P = 0.04). The lag time for perceiving capsaicin infusion was positively correlated with total sleep time (r = 0.43, P = 0.03). CONCLUSIONS: We have shown that GERD patients with sleep disturbance have significantly enhanced heartburn perception to capsaicin infusion as compared with those with normal sleep. Our findings suggest that sleep disturbance is associated with esophageal hypersensitivity to capsaicin infusion in patients with GERD.

Effects of esophageal capsaicin instillation on acid induced excitation of secondary peristalsis in humans.

BACKGROUND/AIM: Esophageal instillation of capsaicin or hydrochloric acid enhances secondary peristalsis. Our aim was to investigate whether intra-esophageal capsaicin infusion can influence symptom perception and physiological alteration of secondary peristalsis subsequent to acid infusion. METHODS: Secondary peristalsis was induced by mid-esophagus injections of air in 18 healthy subjects. Two different sessions including esophageal infusion of hydrochloric acid (0.1 N) following pretreatment with saline or capsaicin-containing red pepper sauce were randomly performed at least one week apart. Symptoms of heartburn and secondary peristalsis were determined and compared between each study session. RESULTS: The intensity of heartburn symptom subsequent to acid infusion was significantly reduced after capsaicin infusion as compared with saline infusion (54 ± 3 vs 61 ± 3; P = 0.03). Capsaicin infusion significantly increased the threshold volume of secondary peristalsis to rapid air injections subsequent to esophageal acid infusion (8.0 ± 0.5 mL vs 4.4 ± 0.3 mL; P < 0.0001). The frequency of secondary peristalsis subsequent to acid infusion was significantly decreased after capsaicin infusion as compared to saline infusion (70% [60-82.5%] vs 80% [70-90%]; P = 0.03). Capsaicin infusion significantly decreased the pressure wave amplitude of secondary peristalsis subsequent to acid infusion during rapid air injections (90.6 ± 8.7 mmHg vs 111.1 ± 11.1 mmHg; P = 0.03). CONCLUSIONS: Capsaicin appears to desensitize the esophagus to acid induced excitation of secondary peristalsis in humans, which is probably mediated by rapidly adapting mucosal mechanoreceptors. High capsaicin-containing diet might attenuate normal physiological response to abrupt acid reflux by inhibiting secondary peristalsis.

Decrease in cytochrome c oxidase reserve capacity diminishes robustness of Drosophila melanogaster and shortens lifespan.

The phenotypic effects of under- and over-expression of CcO (cytochrome c oxidase) regulatory subunits IV and Vb were examined in Drosophila melanogaster in order to test further the hypothesis that suppression of the activities of mitochondrial ETC (electron-transport chain) oxidoreductases retards the aging process and extends lifespan. Underexpression of both CcO subunits, induced by RNAi, resulted in decreases in the respective mRNA and protein levels, CcO holoenzyme activity, rate of mitochondrial respiration, walking speed and the lifespan of fruitflies. Overexpression of CcO IV or Vb in young fruitflies increased the amount of mRNA, but had no effect on the protein level or CcO catalytic activity. On the other hand, in older fruitflies, overexpression of CcO Vb, but not CcO IV, elevated the mRNA and protein amounts as well as the CcO holoenzyme activity, thereby preventing the typical age-related decline in CcO activity. Nevertheless, lifespans of the fruitflies overexpressing CcO IV or Vb were neither extended nor shortened. Our results demonstrate that: (i) the suppression of CcO function exerts deleterious rather than benign effects on fitness and survival, and (ii) the structure/function of CcO, an ETC oxidoreductase, can be 're-engineered' in vivo.

The effect of peroxiredoxin 4 on fly physiology is a complex interplay of antioxidant and signaling functions.

Peroxiredoxin 4 (Prx4) has been implicated in a wide variety of biological processes, including development, progression of cancer, inflammation, and antioxidant function. The purpose of this study was to provide further insight into its multiple roles at the whole-animal level, using Drosophila. Reduced expression of dPrx4 (up to 90%) resulted in greater sensitivity to oxidative stress, an elevated H2O2 flux, and increases in lipid peroxidation, but no effect on longevity. Overexpression at low levels (<2-fold) gave reduced levels of oxidative damage and tended to show an increase in longevity. Flies expressing dPrx4 globally at high levels (>5-fold) had a dramatically reduced life span (by 20-80%) and increased apoptosis. Analysis of these overexpressors revealed an aberrant redistribution of the dPrx4 protein from the endoplasmic reticulum (ER) to cytosol and hemolymph. In addition to the known proapoptotic effects of the cytosolic form of dPrx4, dPrx4 overexpression triggered an NF-κB-mediated proinflammatory response, similar to that observed in cells under ER stress or when microbially challenged. Finally, we provide the first evidence that dPrx4, on secretion into the hemolymph, elicits a JAK/STAT-mediated response. The effects on fly survival and homeostasis appear to represent a combination of differential effects dictated in large part by dPrx4 subcellular and tissue-specific localization.

Kawasaki Disease in the Time of COVID-19 and MIS-C: The International Kawasaki Disease Registry.

BACKGROUND: Patients with multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) have overlapping clinical features. We compared demographics, clinical presentation, management, and outcomes of patients according to evidence of previous SARS-CoV-2 infection. METHODS: The International Kawasaki Disease Registry (IKDR) enrolled KD and MIS-C patients from sites in North, Central, and South America, Europe, Asia, and the Middle East. Evidence of previous infection was defined as: Positive (household contact or positive polymerase chain reaction [PCR]/serology), Possible (suggestive clinical features of MIS-C and/or KD with negative PCR or serology but not both), Negative (negative PCR and serology and no known exposure), and Unknown (incomplete testing and no known exposure). RESULTS: Of 2345 enrolled patients SARS-CoV-2 status was Positive for 1541 (66%) patients, Possible for 89 (4%), Negative for 404 (17%) and Unknown for 311 (13%). Clinical outcomes varied significantly among the groups, with more patients in the Positive/Possible groups presenting with shock, having admission to intensive care, receiving inotropic support, and having longer hospital stays. Regarding cardiac abnormalities, patients in the Positive/Possible groups had a higher prevalence of left ventricular dysfunction, and patients in the Negative and Unknown groups had more severe coronary artery abnormalities. CONCLUSIONS: There appears to be a spectrum of clinical features from MIS-C to KD with a great deal of heterogeneity, and one primary differentiating factor is evidence for previous acute SARS-CoV-2 infection/exposure. SARS-CoV-2 Positive/Possible patients had more severe presentations and required more intensive management, with a greater likelihood of ventricular dysfunction but less severe coronary artery adverse outcomes, in keeping with MIS-C.