[Heart involvement in multisystem inflammatory syndrome in children correlated with SARS-CoV-2 infection: a review by ANMCO/SICP]. / Le manifestazioni cardiache nella sindrome multisistemica infiammatoria del bambino correlate all'infezione da SARS-CoV-2: una rassegna a cura di ANMCO/SICP.

Acute clinical manifestations of COVID-19 are generally less severe in childhood, however a proportion of them can develop a severe systemic hyperinflammatory syndrome after SARS-CoV-2 infection, known as the multisystem inflammatory syndrome (multisystem inflammatory syndrome in children, MIS-C). Cardiovascular manifestations in MIS-C are frequent (34-82%), including myocardial dysfunction, coronary artery dilation or aneurysms, arrhythmias, conduction abnormalities, pericarditis and valvulitis. The most affected cases can develop cardiogenic shock needing intensive care unit admission, inotropic support and sometimes even mechanical circulatory support. The elevation of myocardial necrosis markers, the frequently transient left ventricular systolic dysfunction and the presence of changes on magnetic resonance imaging, support the hypothesis of an immune-mediated post-viral pathogenesis similar to myocarditis. Although MIS-C shows excellent short-term survival, further studies are needed to demonstrate complete reversibility of residual subclinical heart damage.

Presence of coronary aneurysms during Kawasaki Disease (KD) correlates with lower levels of autoantibodies to both full form and spliced variant of immune regulator Del-1.

Kawasaki disease (KD), a rare multisystem inflammatory condition that predominantly affects children under six years of age, is the leading cause of childhood-acquired heart disease in developed countries. The pathogenesis is unknown, but studies support that an infectious stimulus triggers an autoimmune reaction in a genetically susceptible child. Recent studies demonstrated an association with autoantibody response to Del-1 (also known as EDIL3) in children with KD. Del-1 is an extracellular matrix protein that is expressed both in macrophages and vascular endothelium. Del-1 has an anti-inflammatory role by preventing leucocyte migration to inflammatory sites. Del-1 has two expression variants and genetic variants of Del-1 have been associated with the risk of intracranial aneurysms. Due to the physiologic plausibility for a role during KD, we chose to assess if autoantibodies against DEL-1 are seen in a larger cohort of children with KD and to assess if responses correlated to aneurysm formation. Contrary to prior findings, in comparison to febrile controls, autoantibodies were not overall higher in children with KD. Elevation in Post-IVIG samples in comparison to pre-IVIG and convalescent samples supports the commonality of anti-Del-1 antibodies. Autoantibodies were notably lower in children with KD who had coronary Z score elevations in comparison to those who did not.

Multiple MIS-C Readmissions and Giant Coronary Aneurysm After COVID-19 Illness and Vaccination: A Case Report.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) rarely involves delayed giant coronary aneurysms, multiple readmissions or occurrence after COVID-19 vaccination. METHODS: We describe a child with all 3 of these unusual features. We discuss his clinical presentation, medical management, review of the current literature and CDC guidance recommendations regarding further vaccinations. RESULTS: A 5-year-old boy had onset of MIS-C symptoms 55 days after COVID-19 illness and 15 days after receiving his first BNT162b2 COVID-19 vaccination. He was admitted 3 times for MIS-C, and twice after his steroid dose was tapered. On his initial admission, he was given intravenous immunoglobulin and steroids. During his second admission, new, moderate coronary dilation was noted, and he was treated with intravenous immunoglobulin and steroids. At his last admission, worsening coronary dilation was noted, and he was treated with infliximab and steroids. During follow-up, he had improvement in his coronary artery dilatation. However, his inflammatory markers increased after steroid wean, and his steroid taper was further extended, after which time his inflammatory markers improved. This is the only such reported case of a patient who was admitted 3 times for MIS-C complications after COVID-19 vaccination. CONCLUSION: MIS-C rarely involves delayed giant coronary aneurysms, multiple readmissions, or occurrence after COVID-19 vaccination. Whether our patient's COVID-19 vaccine 6 weeks after COVID-19 illness contributed to his MIS-C is unknown. After consultation with the CDC-funded Clinical Immunization Safety Assessment Project, the patient's care team decided against further COVID-19 vaccination until at least 3 months post normalization of inflammatory markers.

Emerging Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome Associated With COVID-19 in Children.

Multisystem inflammatory syndrome in children (MIS-C) has emerged as a rare delayed hyperinflammatory response to SARS-CoV-2 infection and causes severe morbidity in the pediatric age group. Although MIS-C shares many clinical similarities to Kawasaki disease (KD), important differences in epidemiologic, clinical, immunologic, and potentially genetic factors exist and suggest potential differences in pathophysiology and points to be explored and explained. Epidemiologic features include male predominance, peak age of 6 to12 years, and specific racial or ethnicity predilections. MIS-C is characterized by fever, prominent gastrointestinal symptoms, mucocutaneous manifestations, respiratory symptoms, and neurologic complaints, and patients often present with shock. Cardiac complications are frequent and include ventricular dysfunction, valvular regurgitation, pericardial effusion, coronary artery dilation and aneurysms, conduction abnormalities, and arrhythmias. Emerging evidence regarding potential immunologic mechanisms suggest that an exaggerated T-cell response to a superantigen on the SARS-CoV-2 spike glycoprotein-as well as the formation of autoantibodies against cardiovascular, gastrointestinal, and endothelial antigens-are major contributors to the inflammatory milieu of MIS-C. Further studies are needed to determine both shared and distinct immunologic pathway(s) that underlie the pathogenesis of MIS-C vs both acute SARS-CoV-2 infection and KD. There is evidence to suggest that the rare risk of more benign mRNA vaccine-associated myopericarditis is outweighed by a reduced risk of more severe MIS-C. In the current review, we synthesize the published literature to describe associated factors and potential mechanisms regarding an increased risk of MIS-C and cardiac complications, provide insights into the underlying immunologic pathophysiology, and define similarities and differences with KD.

Giant coronary aneurysms in an infant: Dilemma of MIS-C.

COVID-19 related multisystem inflammatory syndrome in children (MIS-C) can present with cardiovascular complications like shock, arrhythmias, pericardial effusion, and coronary artery dilatation. The majority of MIS-C associated coronary artery abnormalities are dilation or small aneurysms which are transient and resolve in a few weeks. We present here a case of a 3-month-old child who was noted to have giant aneurysms of her coronary arteries (LAD and RCA) 26 days after testing positive for COVID-19. She was treated with IVIG, infliximab, and glucocorticoids along with aspirin, clopidogrel, and enoxaparin. She did not show any signs of coronary ischemia or cardiac dysfunction but continued to have persistent giant coronary artery aneurysms involving the LAD (z-score ∼35) and RCA (z-score ∼30). This study emphasizes the importance of early detection and aggressive management of MIS-C to prevent potentially life-threatening consequences.

Rebound multi-system inflammatory syndrome in children (MIS-C): A case report of an extremely rare phenomenon (preprint)

Background: Multi-system inflammatory syndrome in children (MIS-C) is a newly defined clinical syndrome characterized by systemic inflammation, fever, and multi-organ dysfunction related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While MIS-C is familiar to most physicians, recurrent and rebound cases of MIS-C are extremely rare, with only two such cases reported to date. Case presentation: Here, we report the case of a five-month-old boy diagnosed with rebound MIS-C (19 days apart), with the second episode being more severe and featuring a right coronary artery aneurysm. The immunodeficiency workup returned normal. Standard MIS-C treatment protocols were followed in both episodes, eventually yielding an excellent outcome. The patient remained well within 12 months of follow-up. Conclusions: We conclude that longer and closer follow-ups of MIS-C patients may be needed, perhaps with a more aggressive treatment protocol to prevent a rebound or recurrence of the disease, though further studies are required to guide clinical decision-making.

Cardiac effects of multisystem inflammatory syndrome in children: One-year follow-up.

AIM: Cardiovascular involvement is common among children with multisystem inflammatory syndrome (MIS-C) and can cause shock and death. In this study, we evaluated the early and long-term cardiac effects of MIS-C. METHODS: In this observational cohort study, we included all children treated for MIS-C from October 2020 to November 2021 in the Department of Paediatric Infectious Disease at Cukurova University School of Medicine Hospital. The patients underwent serial echocardiographical evaluation during hospitalisation and at 1, 3, 6 and 12 months after discharge. The patients were evaluated using Holter monitorisation between 4 and 6 months and using cardiac magnetic resonance imaging at 6 months and thereafter. RESULTS: Twenty-six patients diagnosed with MIS-C and with a median age of 84 months were included. Cardiac involvement was found in 19 (73.1%) patients. At initial echocardiographic evaluation, the mean ejection fraction value of the patients was 56.7% (range: 30-75). Coronary artery dilatation was detected in two (7.7%) patients, and mitral regurgitation persisted in only one patient by month 3. Treatment was started in two (7.7%) patients due to ventricular arrhythmia. Cardiac magnetic resonance imaging was performed in 13 (50%) patients at a median of 6 months (range: 5-9). The cardiac magnetic resonance imaging findings were consistent with possible interstitial fibrosis in two (7.7%) patients. CONCLUSION: Our results showed that cardiac involvement of patients improved rapidly with treatment, as indicated by previous studies. However, during the 1-year follow-up, frequent extraventricular systole was detected in two patients, one of whom initially did not show cardiac involvement. Moreover, possible interstitial fibrosis was detected in the cardiac magnetic resonance imaging (MRI) evaluation of two patients. In particular, we believe that these findings may be useful to evaluate critically ill paediatric patients and patients with severely low EF with cardiac MRI in their follow-up.

Characteristics and Outcomes of Multisystem Inflammatory Syndrome in Children: A Multicenter, Retrospective, Observational Cohort Study in Mexico (preprint)

Multisystem inflammatory syndrome in children temporally associated with coronavirus disease 2019 (MIS-C), a novel hyperinflammatory condition secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with severe outcomes such as coronary artery aneurysm and death. This multicenter, retrospective, observational cohort study including eight centers in Mexico, aimed to describe the clinical characteristics and outcomes of patients with MIS-C. Patient data were evaluated using latent class analysis to categorize patients into three phenotypes: toxic shock syndrome-like (TSSL)-MIS-C, Kawasaki disease-like (KDL)-MIS-C, and nonspecific MIS-C (NS-MIS-C). Risk factors for adverse outcomes were estimated using multilevel mixed-effects logistic regression. The study included 239 patients with MIS-C, including 61 (26%), 70 (29%), and 108 (45%) patients in the TSSL-MIS-C, KDL-MIS-C, and NS-MIS-C groups, respectively. Fifty-four percent of the patients were admitted to the intensive care unit, and 42%, 78%, and 41% received intravenous immunoglobulin, systemic glucocorticoids, and anticoagulants, respectively. Coronary artery dilatation and aneurysm were found in 5.7% and 13.2% of the patients, respectively. The rate of mortality due to SARS-CoV-2-related factors was 4.6%. Delay of [≥]10 days in hospital admission was associated with coronary artery aneurysm or dilatation (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.2- 2.0). Age [≥] 10 years (OR 5.6, 95% CI 1.4- 2.04), severe underlying condition (OR 9.3, 95% CI 2.8- 31.0), platelet count < 150,000/mm3 (OR 4.2, 95% CI 1.2- 14.7), international normalized ratio > 1.2 at admission (OR 3.8, 95% CI 1.05- 13.9), and serum ferritin concentration > 1500 mg/dL (OR 52, 95% CI 5.9- 463) were risk factors for death.

Coronary artery aneurysm presenting as ST-elevation myocardial infarction in a man with coronavirus disease 2019: a case report.

BACKGROUND: Patients with underlying cardiovascular risk factors have worse clinical outcomes when they have coronavirus disease. In addition, a reduced workload of cardiovascular emergencies has been reported during the coronavirus pandemic due to patients' reluctance to attend hospitals for fear of contracting the disease. Regional health service reorganization, separating hospitals into coronavirus and non-coronavirus can mitigate this effect. However, the effectiveness of this approach on outcomes and patient satisfaction is unknown. CASE PRESENTATION: A 35-year-old Pakistani man with acute ST myocardial infarction was found to have thrombosis of the right coronary artery aneurysm and concomitant coronavirus disease. He had percutaneous coronary angiography and thrombus removal, and was transferred to a coronavirus hospital for the management of the infection. Due to the large size of the aneurysm, he was considered for surgical intervention. Following discharge from the coronavirus hospital and a period of stay at the isolation center, he failed to keep his cardiology follow-up appointment. CONCLUSION: This case illustrates an unusual cause of myocardial infarction in a patient with coronavirus infection whose care may have been adversely affected by the healthcare system restructuring.

Immune and non-immune mechanisms that determine vasculitis and coronary artery aneurysm topography in Kawasaki disease and MIS-C.

The overlap between multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) including coronary artery aneurysms (CAA) and broadly shared gastrointestinal and mucocutaneous disease is poorly defined. In this perspective, we highlight common age-related extravascular epicardial microanatomical and immunological factors that might culminate in CAA expression in both MIS-C and KD. Specifically, the coronary vasa vasorum originates outside the major coronary arteries. Widespread inflammation in the epicardial interstitial compartment in shared between KD and MIS-C. Age-related changes in the neonatal and immature coronary vasculature including the impact of coronary artery biomechanical factors including coronary vessel calibre, age-related vessel distensibility, flow, and vessel neurovascular innervation may explain the decreasing CAA frequency from neonates to older children and the virtual absence of CAA in young adults with the MIS-C phenotype. Other KD and MIS-C features including mucocutaneous disease with keratinocyte-related immunopathology corroborate that disease phenotypes are centrally influenced by inflammation originating outside vessel walls but a potential role for primary coronary artery vascular wall inflammation cannot be excluded. Hence, common extravascular originating tissue-specific responses to aetiologically diverse triggers including superantigens may lead to widespread interstitial tissue inflammation characteristically manifesting as CAA development, especially in younger subjects. Given that CAA is virtually absent in adults, further studies are needed to ascertain whether epicardial interstitial inflammation may impact on both coronary artery physiology and cardiac conduction tissue and contribute to cardiovascular disease- a hitherto unappreciated consideration.

Coronavirus disease 2019-related Kawasaki syndrome: a case report.

BACKGROUND: Coronavirus disease 2019 has changed the pattern of some diseases in the world, especially in pediatrics. Despite data suggesting that the pediatric population is less affected by coronavirus disease-19 infection, new concerns have been raised owing to reported cases with hyperinflammatory conditions such as Kawasaki disease. CASE PRESENTATION: We report herein the case of a pediatric patient diagnosed and treated for classic Kawasaki disease in the setting of confirmed coronavirus disease 2019 infection. She was an 8-year-old, previously healthy, and fully immunized Iranian girl who initially presented to the pediatric emergency department with 5 days of intermittent fever, followed by abdominal pain, nausea, and vomiting. She was admitted for fever and abdominal pain to the surgery service of Akbar Hospital with suspected appendicitis. CONCLUSIONS: This case report may serve as a useful reference to other clinicians caring for pediatric patients affected by coronavirus disease 2019 infection. Standard therapeutic interventions for Kawasaki disease must be performed to prevent critical coronary aneurysm-related complications in the coronavirus disease 2019 era.

Vasoactive Endothelial Growth Factor and Heat Shock Protein Gene Expression Response in Kawasaki Disease Associated Coronary Arteritis (preprint)

Background and Aim Coronary involvement in Kawasaki Disease (KD), whether its after SARS-CoV2 infection or not, can result in significant complications. There is the risk of aneurysm formation associated with inflammation and an unremitting fever. We wished to study the Vasoactive Endothelial Growth Factor (VEGF) and Heat Shock Response from a gene-expression perspective. Thereby aiming to furnish to insights that might be useful in the treatment of Kawasaki Disease. Method KD datasets based on previous work, were selected including microarray studies KD1 (GSE63881), KD2 (GSE73461), KD3 (GSE68004) and the RNAseq dataset KD4 (GSE64486) from the NCBI online repository. Based on clinical literature. HSP genes shown to be associated with angiogenesis were chosen for analysis as well as gene expression for VEFGA and VEGFB. Further in order to gain an impression of inflammatory patterns, gene expression for NFKB1 and TNF were also chosen. Tools for analysis included Gene Set Expression Analysis (GSEA). A KEGG pathway, outlining a relationship between VEGF and endothelial migration and proliferation was assumed. Results A KD dataset showed increased VEGFA and decreased VEGFB in acute versus convalescent samples. In all three KD datasets, HSPA1A and HSBAP1 genes were upregulated in acute versus convalescent samples. In KD4, cases of KD versus controls, VEGFB was down-regulated (p = 4.932e-02) and HSPBAP1 up-regulated (p = 1.202e-03). GSEA of KD1, KD2 and KD3, using Hallmark gene sets, suggested an inflammatory response with TNFA signaling via NFKB, IL6 JAK STAT 3 signaling, apoptosis, angiogenesis, and unfolded protein response. Conclusions A novel application of a model of VEGF and HSP to KD was presented. Coronary pathogenesis based on VEGF and HSP was explored. The ability to follow angiogenesis at the molecular level using a VEGF-HSP model may have therapeutic implications. Further, the significance of gene expression between VEGFA, VEGFB in KD and the relationship of HSP gene expression to angiogenesis in KD requires further study.

Deep immune profiling uncovers novel associations with clinical phenotypes of Multisystem Inflammatory Syndrome in Children (MIS-C) (preprint)

Multisystem Inflammatory Syndrome in Children (MIS-C) is a systemic inflammatory condition that follows SARS-CoV2 infection or exposure in children. Clinical presentations are highly variable and include fever, gastrointestinal (GI) disease, shock, and Kawasaki Disease-like illness (MIS-C/KD). Compared to patients with acute COVID, patients with MIS-C have a distinct immune signature and expansion of TRVB11 expressing T cells. However, the relationship between immunological and clinical phenotypes of MIS-C is unknown. Here, we measured serum biomarkers, TCR repertoire, and SARS-CoV2-specific T cell responses in a cohort of 76 MIS-C patients. Serum biomarkers associated with macrophage and Th1 activation were elevated in patients with shock, consistent with previous reports. Significantly increased SARS-CoV-2-induced IFN-{gamma}, IL-2, and TNF- production were seen in CD4+ T cells from patients with neurologic involvement and respiratory failure. Diarrhea was associated with a significant reduction in shock-associated serum biomarkers, suggesting a protective effect. TRVB11 usage was highly associated with MIS-C/KD and coronary aneurysms, suggesting a potential biomarker for these manifestations in MIS-C patients. By identifying novel immunologic associations with the different clinical phenotypes of MIS-C, this study provides insights into the clinical heterogeneity of MIS-C. These unique immunophenotypic associations could provide biomarkers to identify patients at risk for severe complications of MIS-C, including shock and MIS-C/KD.

Mild coronary artery dilatation developed in some children with mild COVID-19 but completely regressed within 3 months.

AIM: We studied the incidence and time course of any coronary artery changes in children up to 2 years of age who were hospitalised with mild COVID-19. METHODS: This was a single-centre prospective study of 29 children (19 males) with a median age of 3 months and interquartile range (IQR) of 1.6-4.3 months. They were admitted to a Greek University hospital for mild COVID-19 from 1 March to 30 December 2021. Three echocardiographic evaluations were performed at a median (IQR) of 19 (16-24) days, 82 (75-89) days and 172 (163-197) after the first symptoms. The prevalence of coronary artery dilation, regression, and changes was documented. RESULTS: Coronary artery dilation was present in 3 (10.3%) cases at the first evaluation, with complete regression at the second. Regression was observed in 18/24 (75%) cases with follow-up data and 9 (31%) demonstrated significant z-score changes of >2. Coronary artery changes in any segment at any time were documented in 18/29 (62%) of the patients. CONCLUSION: Cases of transient and very mild coronary artery dilatation following mild COVID-19 completely regressed within 3 months. Large-scale studies are needed to document the extent and time course of coronary artery dilation following paediatric COVID-19.

Medium-Term Cardiac Outcomes in Young People with Multi-system Inflammatory Syndrome: The Era of COVID-19.

Multi-system inflammatory syndrome in children (MIS-C) causes widespread inflammation including a pancarditis in the weeks following a COVID infection. As we prepare for further coronavirus surges, understanding the medium-term cardiac impacts of this condition is important for allocating healthcare resources. A retrospective single-center study of 67 consecutive patients with MIS-C was performed evaluating echocardiographic and electrocardiographic (ECG) findings to determine the point of worst cardiac dysfunction during the admission, then at intervals of 6-8 weeks and 6-8 months. Worst cardiac function occurred 6.8 ± 2.4 days after the onset of fever with mean 3D left ventricle (LV) ejection fraction (EF) 50.5 ± 9.8%. A pancarditis was typically present: 46.3% had cardiac impairment; 31.3% had pericardial effusion; 26.8% demonstrated moderate (or worse) valvar regurgitation; and 26.8% had coronary dilatation. Cardiac function normalized in all patients by 6-8 weeks (mean 3D LV EF 61.3 ± 4.4%, p < 0.001 compared to presentation). Coronary dilatation resolved in all but one patient who initially developed large aneurysms at presentation, which persisted 6 months later. ECG changes predominantly featured T-wave changes resolving at follow-up. Adverse events included need for ECMO (n = 2), death as an ECMO-related complication (n = 1), LV thrombus formation (n = 1), and subendocardial infarction (n = 1). MIS-C causes a pancarditis. In the majority, discharge from long-term follow-up can be considered as full cardiac recovery is expected by 8 weeks. The exception includes patients with medium sized aneurysms or greater as these may persist and require on-going surveillance.

Cyclosporine for the treatment of multisystem inflammatory syndrome in children with coronary artery aneurysms.

Multisystem inflammatory syndrome in children (MIS-C) is a newly described syndrome related to the COVID-19, resembling other known aetiologies, including Kawasaki disease. Cardiovascular involvement is common; left ventricle dysfunction and coronary artery aneurysm (CAA) are also observed. Many treatment guidelines recommend using intravenous immunoglobulin (IVIG) alone or with glucocorticoids as the first-line therapy. Biological agents, such as anakinra, are recommended for refractory cases, but the evidence is still accumulating. Moreover, the use of other treatment agents can be beneficial, especially when anakinra is unavailable. Here, we report the case of a 9-year-old girl who presented with MIS-C with CAAs. She received cyclosporine because two rounds of IVIG treatment were ineffective and the use of anakinra is not approved in Japan. Her cytokine profile showed that cyclosporine prevented exacerbation. The case highlights that cyclosporine therapy can be an option for the treatment of refractory MIS-C with CAA.

Monster LCX Fistula Closure by Vascular Plug in a Patient with Post- Covid 19 Myocardial Infarction (preprint)

This report presents a man with a huge coronary fistula, connecting Left Circumflex coronary artery to right ventricle. During the follow-up, the patient developed progressive symptoms of heart failure nonresponsive to medical treatment. Therefore, an endovascular closure with vascular plug was successfully done for him.

Giant Coronary Aneurysms in an Infant: Dilemma of MIS-C (preprint)

COVID-19 related MIS-C (Multisystem inflammatory syndrome in children) can present with cardiovascular complications like shock, arrhythmias, pericardial effusion, and coronary artery dilatation. The majority of MIS-C associated coronary artery abnormalities are dilation or small aneurysms which are transient and resolve in a few weeks[[1, 2]](#ref-0001). We present here a case of a 3-month-old child who was noted to have giant aneurysms of her coronary arteries (LAD and RCA) twenty-six days after testing positive for COVID-19. She was treated with IVIG, infliximab, and glucocorticoids along with aspirin, clopidogrel and enoxaparin. She did not show any signs of coronary ischemia or cardiac dysfunction but continued to have persistent giant coronary artery aneurysms involving the LAD (z-score ~35) and RCA (z-score ~30) [Fig. 1]. This study emphasizes the importance of early detection and aggressive management of MIS-C to prevent potentially life-threatening consequences.

Evaluation of the association between coronary artery aneurysm and concomitant infection in patients with Kawasaki disease (preprint)

Purpose: Multisystem inflammatory syndrome in children, which has overlapping clinical features with Kawasaki disease (KD), has generated considerable interest in the relationship between KD and infectious diseases during the ongoing global outbreak of coronavirus disease 2019. However, few studies have focused on the relationship between KD and concomitant infection, and reports on the relationship between infections and recovery from coronary artery aneurysms (CAA) are even rarer. Methods: : Patients were classified into case and control groups according to the results of their pathogen examinations, and the baseline characteristics of the two groups were compared. The Kaplan–Meier survival analysis was used to compare the medium-term recovery time of CAA between patients with and without infections, and multivariable analyses were performed to evaluate potential risk factors associated with CAA without recovery between 1 and 2 years of follow-up. Results: : A total of 353 pediatric patients with KD were included, of whom 83 (23.5%) had confirmed co-infection. There were no significant differences in patients’ response to treatment and coronary artery outcome when compared between patients with and without infections. Among the 90 patients diagnosed with CAA, 20 (22.2%) had confirmed co-infection, and no significant differences were observed in coronary artery changes from baseline at 2 weeks, 4 weeks, and 3 months in patients with CAA with and without infections. The estimated median time (6 months, 95%CI:1.920–10.080) was higher in the CAA co-infected group than in the CAA non-infected group (3 months, 95%CI:2.366–3.634), with no significant difference. Multivariate analysis revealed that a high Z-score of the coronary artery internal diameter at 1 month after onset was significantly associated with CAA without recovery. The Z score of the left main coronary artery was ≥3.215 with an 89% sensitivity and 77% specificity in predicting CAA without recovery within 1 year of onset. The Z score of the right coronary artery was ≥3.845 with a 64% sensitivity and 98% specificity in predicting CAA without recovery within 1 year of onset and with an 83% sensitivity and 88% specificity within 2 years of onset. Conclusions: : Concomitant infection with KD diagnosis did not affect the patients’ response to IVIG treatment and coronary artery outcome when compared with patients without infections; however, the time to coronary artery normalization was not notably prolonged in CAA patients with infections, but a larger maximum Z score at 1 month after onset was a risk factor significantly associated with coronary artery dilatation without recovery within 2 years of onset.