Guide for cardiological referral for patients with paediatric multisystemic inflammatory syndrome and Kawasaki disease associated with SARS-CoV-2 / Guía para referencia cardiológica de pacientes con síndrome inflamatorio multisistémico pediátrico y enfermedad por Kawasaki asociados al SARS-CoV-2

We present an institutional guide for a referral to the specialized care center and initial management of pediatric patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with severe manifestations of pediatric inflammatory multisystemic syndrome or symptoms similar to Kawasaki syndrome, and who must have a multidisciplinary approach to ensure adequate treatment and safety for the team of Health.

Presentamos una guía para la referencia al centro de atención especializada y el manejo inicial de pacientes pediátricos infectados por el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) con manifestaciones graves del síndrome multisistémico inflamatorio pediátrico o síntomas semejantes al síndrome de Kawasaki y que deben tener un abordaje multidisciplinario para garantizar un adecuado tratamiento y la mayor seguridad para el equipo de salud.

Multisystemic Inflammatory Syndrome in Children and Kawasaki Disease: Parallels in Pathogenesis and Treatment.

PURPOSE OF REVIEW: Since it first appeared, multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been compared to Kawasaki disease (KD). Although there were early parallels between MIS-C and KD, key differences emerged over time. Here, we aim to compare the pathogenesis, clinical presentation, treatment, and outcomes of MIS-C and KD. RECENT FINDINGS: In this article, we review and compare MIS-C and KD, highlighting differentiating features. We discuss the epidemiological and immunological factors along with clinical and laboratory features which discern MIS-C from KD. We also compare treatment and our understanding of long-term outcomes. Though parallels exist between MIS-C and KD, distinguishing the two is important for clinical management of patients, counseling about natural history, and determining long-term monitoring. While both MIS-C and KD are characterized by profound inflammation and inflammatory vasculopathy, further study is needed to determine whether they are distinct immunopathogenic disorders.

Clinical features of multisystem inflammatory syndrome in children.

PURPOSE OF REVIEW: To review diagnosis, clinical characteristics and treatment of multisystem inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RECENT FINDINGS: MIS-C emerged in spring 2020 as a hyperinflammatory syndrome following SARS-CoV-2 exposure in children. Despite growing awareness of MIS-C, diagnosis remains challenging due to the range of phenotypes and severity. Fever accompanied by shock, cardiac dysfunction, gastrointestinal symptoms, or mucocutaneous signs suggestive of Kawasaki disease, especially in the presence of known or suspected coronavirus disease 2019 exposure, should trigger consideration of MIS-C. However, clinical presentations are highly varied and may overlap with other infectious diseases. Clinicians must maintain a high index of suspicion for MIS-C and be aware that patients may develop coronary artery aneurysms and myocarditis even with few or no Kawasaki disease symptoms. More precise diagnostic criteria and specific biomarkers are needed to aid diagnosis. Intravenous immunoglobulin (IVIG) is first-line therapy, and steroids should be considered as initial adjunctive treatment for patients with severe manifestations or other risk factors. Prompt treatment is essential, as patients may worsen acutely, though overall prognosis is reassuring. SUMMARY: MIS-C associated with SARS-CoV-2 has varied clinical manifestations. Clinicians must be aware of the common presentation and potential for decompensation and cardiac sequalae to guide appropriate evaluation and treatment.

Acute phase of Kawasaki disease: a review of national guideline recommendations.

Key aspects of the medical management of Kawasaki disease (KD) are not yet supported by a high evidence level, thus making room for individual recommendations. We performed a structured comparison of existing international KD guidelines to analyze potential differences in the implementation of evidence-based KD recommendations regarding diagnosis and therapy. To identify country-specific guidelines, we took a multilateral approach including a comprehensive PubMed literature, online research, and directly contacting national pediatric associations. We then ran a structured guidelines' analysis and evaluated the diagnostic and therapeutic differences in the context of evidence-based medicine. In this structured guideline analysis, we identified nine national and one European guidelines. According to them all, the diagnosis of KD still relies on its clinical presentation with no reliable biomarker recommended. First-line treatment consistently involves only intravenous immunoglobulin (IVIG) therapy. Recommendations in terms of acetylsalicylic acid, corticosteroids, and additional therapeutic options vary considerably. CONCLUSION: According to all guidelines, KD is diagnosed clinically with some variance in defining incomplete KD and being a non-responder to treatment. First-line treatment consistently includes IVIG. Recommendations for additional therapeutic strategies are more heterogeneous. WHAT IS KNOWN: • The diagnosis of KD relies on the clinical presentation, entailing challenges in timely diagnosis. • Other treatment options then IVIG are not supported by a high evidence level, making room for individual recommendations. WHAT IS NEW: • Definition of incomplete KD and being non-responsive to an initial treatment vary to some extent between the national guidelines. • Only IVIG is consistently proposed throughout all guidelines, further therapeutic recommendations vary between the national recommendations.

Prevalence of paediatric hyperinflammatory conditions in paediatric and adolescent hospitalized COVID-19 patients: a systematic review and meta-analysis.

In the milieu of coronavirus disease 2019 (COVID-19), there are increasing reports of paediatric hyperinflammatory conditions (PHICs), including multisystem inflammatory syndrome in children (MIS-C), paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and Kawasaki disease (KD). Few analyses of PHIC prevalence in paediatric and adolescent hospitalized COVID-19 patients exist. The purpose of this study was to perform a meta-analysis to determine a pooled prevalence estimate of PHICs in paediatric and adolescent hospitalized patients admitted for treatment due to COVID-19. Individual studies were retrieved from PubMed/Medline, EMBASE and Cochrane databases. Relevant prevalence, baseline, treatment and outcome data were extracted using a standardized datasheet. The systematic review and meta-analysis were conducted as per the PRISMA and MOOSE guidelines. Overall, 14 studies with 2202 patients admitted for treatment due to COVID-19, among whom 780 were diagnosed with PHICs, were included. The crude estimate of prevalence was 35.42%, and the pooled estimate of prevalence was 29% (random pooled ES = 0.29; 95% CIs = 0.18-0.42; p < 0.0001; z = 7.45). A sizeable proportion of paediatric and adolescent hospitalized patients admitted for treatment due to COVID-19 are diagnosed with a PHIC warranting a high index of clinical suspicion for PHICs. Further studies are required to validate these findings.

Profile of Children with Kawasaki Disease Associated with Tropical Infections.

OBJECTIVE: To describe various infectious triggers for Kawasaki disease (KD) in India. METHODS: A series of 10 children with diagnosed infections who developed KD during their course of illness has been presented. They were diagnosed by the American Heart Association (AHA) 2017 guidelines. Echocardiography was done to check for coronary artery dilation. Treatment was instituted as per standard protocol. RESULTS: Kawasaki disease was diagnosed in 8 boys and 2 girls, aged 1 mo to 11 y. These children were being treated for dengue, chikungunya, SARS-CoV-2, hepatitis A, tuberculosis, brucellosis, disseminated staphylococcal sepsis, scrub typhus, and enteric fever. CONCLUSIONS: Kawasaki disease has been associated with infectious triggers. It should be considered in febrile patients with mucocutaneous involvement or in nonresponsive sepsis, despite adequate therapy.

Recent Insights into COVID-19 in Children and Clinical Recommendations.

Pediatric coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) have been recognized in multiple countries globally. In this review, we provide recent insights into SARS-CoV-2 infection in children from epidemiological, clinical, and laboratory perspectives, including reports on the disease course and therapy. We highlight key features of SARS-CoV-2 infection in children, the relationship between MIS-C and Kawasaki disease, and summarize treatment guidelines for COVID-19 in children from institutional protocols from Colombia, case reports, recommendations based on expert consensus, and official statements from organizations such as the World Health Organization (WHO), United States Center for Disease Control (CDC), Colombian Association of Infectious Diseases, and the Colombian Society of Pediatrics. Finally, we discuss gaps in research with suggestions for future research on the pathogenesis underlying pediatric COVID-19.

Explanations for 10 of the most puzzling aspects of multisystem inflammatory syndrome and other Kawasaki-like diseases.

WHAT IS KNOWN AND OBJECTIVE: An extensively documented multisystem inflammatory syndrome (MIS) has been observed in a small but significant percentage of COVID-19 patients, in some adults but primarily in paediatric patients, and for these patients it is sometimes called MIS-C. COMMENT: Kawasaki disease has also been observed over the last several decades in patients that tested positive for a variety of very virulent pathogens. Several differences and similarities between MIS-C and Kawasaki disease pathology have been observed. Several puzzling aspects of MIS-C, Kawasaki disease and other Kawasaki-like diseases have been discussed, but not yet explained. WHAT IS NEW AND CONCLUSION: An explanatory hypothesis has been presented. Using the hypothesis that a transient or permanent inability to quickly phagocytize antigen-antibody immune complexes created by a novel virulent pathogen infection induces a Type III hypersensitivity immune response and the resulting proteinase exposure and expression of new autoantigens are the fundamental steps for MIS and other Kawasaki-like diseases, it is possible to provide straightforward explanations for at least 10 of the most puzzling aspects of these diseases. The validity of the hypothesis itself is also supported by its ability to provide consistent and straightforward explanations for a large number of these disease aspects. Furthermore, these straightforward explanations and the explanatory hypothesis on which they are based also suggest several potential new treatments, which could possibly be more effective than various treatments in current use.

Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C.

BACKGROUNDMultisystem inflammatory syndrome in children (MIS-C) is a rare but potentially severe illness that follows exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Kawasaki disease (KD) shares several clinical features with MIS-C, which prompted the use of intravenous immunoglobulin (IVIG), a mainstay therapy for KD. Both diseases share a robust activation of the innate immune system, including the IL-1 signaling pathway, and IL-1 blockade has been used for the treatment of both MIS-C and KD. The mechanism of action of IVIG in these 2 diseases and the cellular source of IL-1ß have not been defined.METHODSThe effects of IVIG on peripheral blood leukocyte populations from patients with MIS-C and KD were examined using flow cytometry and mass cytometry (CyTOF) and live-cell imaging.RESULTSCirculating neutrophils were highly activated in patients with KD and MIS-C and were a major source of IL-1ß. Following IVIG treatment, activated IL-1ß+ neutrophils were reduced in the circulation. In vitro, IVIG was a potent activator of neutrophil cell death via PI3K and NADPH oxidase, but independently of caspase activation.CONCLUSIONSActivated neutrophils expressing IL-1ß can be targeted by IVIG, supporting its use in both KD and MIS-C to ameliorate inflammation.FUNDINGPatient Centered Outcomes Research Institute; NIH; American Asthma Foundation; American Heart Association; Novo Nordisk Foundation; NIGMS; American Academy of Allergy, Asthma and Immunology Foundation.

SARS-CoV-2 infection triggering recurrence of Kawasaki disease in a 10-year-old child.

SARS-CoV-2 infection has recently been related to a spectrum of hyper-inflammatory states in children. There is a striking similarity between these hyper-inflammatory states and Kawasaki disease (KD). We present an interesting case of KD recurrence in a 10-year-old child, who had previously developed KD at 4 years of age. His symptoms included fever, maculopapular rash and altered sensorium. Investigations showed noticeably elevated inflammatory markers, and an echocardiography revealed dilated coronary arteries. SARS-CoV-2 IgG antibodies were positive. The child responded dramatically to intravenous immunoglobulin and intravenous methylprednisolone. It is possible that SARS-CoV-2 infection triggered the recurrence of KD in this child who might have been genetically predisposed to KD.

Cardiac pathology and outcomes vary between Kawasaki disease and PIMS-TS.

Overlapping clinical features promoted the discussion of whether Kawasaki disease (KD) and PIMS-TS share pathophysiological features and disease outcomes. Medical records from English patients with KD (2015-02/20, N = 27) and PIMS-TS (02/2020-21, N = 34) were accessed to extract information. Children with PIMS-TS were older and more frequently of minority ethnicity background. They patients more commonly exhibited cytopenias and hyperferritinemia, which associated with diffuse cardiac involvement and functional impairment. In some PIMS-TS cases, cardiac pathology developed late, but outcomes were more favorable. In both, KD and PIMS-TS, baseline coronary diameter was a predictor of outcomes. PIMS-TS treatment more frequently included respiratory and cardiovascular support, and corticosteroids with IVIG. Cardiac involvement in PIMS-TS may be the result of a cytokine storm. Though more severe and diffuse when compared to KD, cardiac involvement of PIMS-TS has a more favorable prognosis, which may, after recovery, mitigate the need for long-term follow up.

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents.

BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.).

Similarities and differences between multiple inflammatory syndrome in children associated with COVID-19 and Kawasaki disease: clinical presentations, diagnosis, and treatment.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading rapidly around the world, while "multisystem inflammatory syndrome in children" (MIS-C) is a new type of syndrome that has now been reported in many countries. Similar and different characteristics between KD and MIS-C have been reported in a variety of literature. We aimed to focus on reviewing clinical presentations, diagnosis, and treatment of KD and MIS-C. METHODS: We searched articles in the electronic databases, including the Cochrane Library database, EMBASE, and MEDLINE with the keywords "multiple inflammatory syndrome" and/or "COVID-19" and/or "Kawasaki disease" and "children". RESULTS: Main presentations of MIS-C and KD include fever, rashes, mucous membrane involvement, conjunctivitis, hands and feet erythema/edema, and cervical lymphadenopathy. However, compared with the highest incidence of KD among some Asian countries, MIS-C is common among Black and Hispanic children. MIS-C is common in older children and teenagers, whereas classic KD is common in children under five years of age. Gastrointestinal symptoms, shock, and coagulopathy are common in MIS-C patients but are not common in classic KD. Cardiac manifestations are more common than KD, including myocarditis with cardiac dysfunction and coronary artery dilation or aneurysms. Severe cases in MIS-C present with vasodilated or cardiogenic shock that requires fluid resuscitation, muscular support, and even mechanical ventilation and extracorporeal membrane oxygenation (ECMO), whereas KD rarely presents with these manifestations and requires these treatments. Increased serum ferritin, leukopenia, lymphopenia and thrombocytopenia are common in MIS-C. However, thrombocytosis is a characteristic feature of KD. Intravenous immunoglobulin (IVIG) and moderate-high dose aspirin are still a standard recommended treatment for KD. In addition to the above-mentioned medications, steroids and biological drugs are frequently used in patients with MIS-C. Most of the children with KD have a good prognosis; however, the long-term clinical outcomes of MIS-C are not clear. CONCLUSIONS: The overall presentation and treatment of MIS-C appear to overlap with KD. However, there are still great differences between the syndromes, and it is controversial to say whether MIS-C is a new entity or is a "severe type" of KD.

Update on SARS-CoV-2 infection in children.

Despite the worldwide spread of SARS-CoV-2 infection (COVID-19), knowledge of the different clinical presentations, ways of transmission, severity and prognosis in children and adolescents is limited. An increasing number of reports describe some of these characteristics in this age range. A non-systematic review was undertaken using MEDLINE (PubMed), LILACS (VHL), Scopus, Web of Science, Cochrane and CAPES Portal databases from 1 January until 30 September 2020 [103] with the search terms SARS-CoV-2, COVID-19, child, children, youth, adolescent and newborn to identify the more recent clinical aspects of SARS-CoV-2 infection in children. In general, SARS-CoV-2 infection in children tends to be asymptomatic or to have mild or moderate signs, and most young ones are infected by family members. Recent reports offer new insights into the disease. Current evidence on SARS-CoV-2 infection in children and adolescents is presented, especially concerning the clinical presentation, imaging and uncommon severe forms of the disease, particularly the COVID-19-associated multisystem inflammatory syndrome. The impact of COVID-19 infection in the perinatal period is described in detail. Knowledge of the various clinical presentations of SARS-CoV-2 in children and adolescents allows the paediatrician to diagnose earlier, monitor warnings signs, implement treatment and, especially, establish preventive measures.Abbreviations : ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; ARF, acute rheumatic fever; CAA, coronary artery aneurysms; CK-MB, creatine kinase-MB; COVID-19, coronavirus disease-2019; HLA, specific human leucocyte antigen; IPC, infection prevention and control; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; MIS-C, COVID-19-associated multisystem inflammatory syndrome; RNA, ribonucleic acid; RT-PCR, reserve transcription-polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; TCT, thoracic computed tomography; TSS, toxic shock syndrome; WHO, World Health Organization.

Multisystem Inflammatory Syndrome in Children in New York State.

BACKGROUND: A multisystem inflammatory syndrome in children (MIS-C) is associated with coronavirus disease 2019. The New York State Department of Health (NYSDOH) established active, statewide surveillance to describe hospitalized patients with the syndrome. METHODS: Hospitals in New York State reported cases of Kawasaki's disease, toxic shock syndrome, myocarditis, and potential MIS-C in hospitalized patients younger than 21 years of age and sent medical records to the NYSDOH. We carried out descriptive analyses that summarized the clinical presentation, complications, and outcomes of patients who met the NYSDOH case definition for MIS-C between March 1 and May 10, 2020. RESULTS: As of May 10, 2020, a total of 191 potential cases were reported to the NYSDOH. Of 95 patients with confirmed MIS-C (laboratory-confirmed acute or recent severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) and 4 with suspected MIS-C (met clinical and epidemiologic criteria), 53 (54%) were male; 31 of 78 (40%) were black, and 31 of 85 (36%) were Hispanic. A total of 31 patients (31%) were 0 to 5 years of age, 42 (42%) were 6 to 12 years of age, and 26 (26%) were 13 to 20 years of age. All presented with subjective fever or chills; 97% had tachycardia, 80% had gastrointestinal symptoms, 60% had rash, 56% had conjunctival injection, and 27% had mucosal changes. Elevated levels of C-reactive protein, d-dimer, and troponin were found in 100%, 91%, and 71% of the patients, respectively; 62% received vasopressor support, 53% had evidence of myocarditis, 80% were admitted to an intensive care unit, and 2 died. The median length of hospital stay was 6 days. CONCLUSIONS: The emergence of multisystem inflammatory syndrome in children in New York State coincided with widespread SARS-CoV-2 transmission; this hyperinflammatory syndrome with dermatologic, mucocutaneous, and gastrointestinal manifestations was associated with cardiac dysfunction.

Phenotype, Susceptibility, Autoimmunity, and Immunotherapy Between Kawasaki Disease and Coronavirus Disease-19 Associated Multisystem Inflammatory Syndrome in Children.

Coronavirus disease-19 (COVID-19) in children is usually mild but some are susceptible to a Kawasaki disease (KD)-like multisystem inflammatory syndrome in children (MIS-C) in the convalescent stage, posing a need to differentiate the phenotype, susceptibility, autoimmunity, and immunotherapy between KD and MIS-C, particularly in the upcoming mass vaccination of COVID-19. Patients with MIS-C are prone to gastrointestinal symptoms, coagulopathy, and shock in addition to atypical KD syndrome with fever, mucocutaneous lesions, lymphadenopathy, and/or cardiovascular events. MIS-C manifests KD-like symptoms that alert physicians to early recognize and adopt the KD treatment regimen for patients with MIS-C. MIS-C linked to COVID-19 teaches us infection-associated autoimmune vasculitis and vice versa. Studies on genetic susceptibility have identified certain human leukocyte antigen (HLA) locus and toll-like receptor (TLR) associated with KD and/or COVID-19. Certain HLA subtypes, such as HLA-DRB1 and HLA-MICA A4 are associated with KD. HLA-B*46:01 is proposed to be the risk allele of severe COVID-19 infection, and blood group O type is a protective factor of COVID-19. The autoimmune vasculitis of KD, KD shock syndrome (KDSS), or MIS-C is mediated by a genetic variant of HLA, FcγR, and/or antibody-dependent enhancement (ADE) resulting in hyperinflammation with T helper 17 (Th17)/Treg imbalance with augmented Th17/Th1 mediators: interleukin-6 (IL-6), IL-10, inducible protein-10 (IP-10), Interferon (IFNγ), and IL-17A, and lower expression of Treg-signaling molecules, FoxP3, and transforming growth factor (TGF-ß). There are certain similarities and differences in phenotypes, susceptibility, and pathogenesis of KD, KDSS, and MIS-C, by which a physician can make early protection, prevention, and precision treatment of the diseases. The evolution of immunotherapies for the diseases has shown that intravenous immunoglobulin (IVIG) alone or combined with corticosteroids is the standard treatment for KD, KDSS, and MIS-C. However, a certain portion of patients who revealed a treatment resistance to IVIG or IVIG plus corticosteroids, posing a need to early identify the immunopathogenesis, to protect hosts with genetic susceptibility, and to combat Th17/Treg imbalance by anti-cytokine or pro-Treg for reversal of the hyperinflammation and IVIG resistance. Based on physiological and pathological immunity of the diseases under genetic susceptibility and host milieu conditions, a series of sequential regimens are provided to develop a so-called "Know thyself, enemy (pathogen), and ever-victorious" strategy for the prevention and immunotherapy of KD and/or MIS-C.

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey.

BACKGROUND: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. METHODS: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. RESULTS: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. CONCLUSION: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

Revised recommendations of the Italian Society of Pediatrics about the general management of Kawasaki disease.

Aim of these revised recommendations for the general management of Kawasaki disease is to encourage its prompter recognition and warrant the most appropriate therapy, based on ascertained scientific data, raising awareness of the complications related to misdiagnosis or delayed treatment. A set of 20 synthetic operative statements is herein provided, including the definition of Kawasaki disease, its protean presentations, clinical course and seminal treatment modalities of all disease phases. The application of these recommendations should improve prognosis of Kawasaki disease and prevent the progression to permanent vascular abnormalities, thereby diminishing morbidity and mortality.

[Recommendation for the recognition, management and follow up of cardiovascular compromise in patients with Pediatric Multisystemic Inflammatory Syndrome associated with COVID-19 (PIMS-CT). Position statement of Chilean Scientific Societies]. / Recomendación para la sospecha, manejo y seguimiento del compromiso cardiovascular en pacientes con Síndrome Inflamatorio Multisistémico en Pediatría asociado a COVID-19 (PIMS-TC). Declaración de Posición de la Sociedad Chilena de Pediatría (SOCHIPE) y Sociedad Chilena de Cardiología y Cirugía Cardiovascular (SOCHICAR).

Since the onset of the SARS-CoV-2 pandemic, the pediatric population has been less affected by the disease both in frequency and severity. However, since April cases of variable presentation and severity characterized by inflammatory phenomena that affect multiple organs have been reported, a condition called Multisystem Inflammatory Syndrome in Children (MIS-C). The literature has reported frequent cardiac involvement, up to 80%. This is characterized by myocardial injury with a significant increase of biomarkers such as serum troponins I and T, BNP, or NT-ProBNP coupled with varying degrees of ventricular dysfunction, pericarditis, valvulitis, and arrhythmias. Coronary compromise has also been described, which can occur in up to 23% of cases, and ranges from dila tations to aneurysms. Inpatient and outpatient cardiology follow-up has been systematized based on the clinical phenotypes such as myocardial injury (myocarditis, valvulitis, pericarditis), shock (usua lly vasoplegic), Kawasaki disease-type manifestations, and those MIS-C that do not comply with the clinic of the previous three. This last group represents the main challenge in the short-, medium- and long-term follow-up, therefore, it is necessary a multidisciplinary team for managing these patients. Considering the high frequency of cardiac compromise in MIS-C, and the importance of reaching a consensus regarding its management and follow-up, we present these recommendations according to the current state of knowledge regarding this recently described pathology.