cord-000627-gvzs9vxr	2011	In the patients, polymorphisms of CLEC5A showed no significant association with coronary artery lesion formation and intravenous immunoglobulin treatment response. This study showed for the first time that polymorphisms of CLEC5A are not associated with susceptibility to KD, coronary artery lesion formation, and intravenous immunoglobulin treatment response in a Taiwanese population. To gain further understanding of the genetic role of CLEC5A in the pathogenesis of KD, the aim of our study was to determine if any CLEC5A SNPs are associated with susceptibility to KD, CAL formation, or IVIG treatment response in Taiwanese children. Additionally, the CLEC5A polymorphisms tested in this study failed to show any significant associations with genotype or allele frequency in the KD patients who showed a response to IVIG treatment (Table 4 ). In conclusion, this study showed for the first time that tSNPs of CLEC5A are not associated with susceptibility to KD, CAL formation, and IVIG treatment response in a Taiwanese population.
cord-003713-n3o8lwu4	2018	title: High antistreptolysin O titer is associated with coronary artery lesions in patients with Kawasaki disease PURPOSE: In Kawasaki disease (KD) patients, coronary artery complications, incomplete and refractory types occur more frequently in patients with streptococcal or other bacterial/viral infections. Therefore, we hypothesized that KD patients diagnosed with concurrent streptococcal infection have poor prognoses, with respect to treatment response and development of coronary artery lesions. CONCLUSION: It is not certain whether acute streptococcal infection may cause KD, but this study revealed that KD with high ASO titers showed higher rates of severe clinical course. A good clinical course group is defined as fever subsiding within 36 hours after the end of first IVIG treatment without any coronary artery abnormalities. All patients in the good clinical course group had complete KD, fevers that subsided within 36 hours after the first IVIG treatment, and normal coronary arteries.
cord-007277-86lynlxn	2005	started their work), but rather that, in some of the earliest work on CoVs during the 1960s, viruses were reported that were then forgotten-viruses that came from adults with respiratory illness, that grew only in human embryonic tracheal organ culture, that caused illness in volunteers, and that were not, or were only distantly, antigenically related to the 2 HCoV species that were subsequently the best studied, HCoV-229E and HCoV-OC43. However, the details from Esper et al.''s study-the seasonal distribution, the percentage of positive samples, the associated respiratory syndromes, and the numbers of infected children at various ages, for example-were heavily influenced by both the particular population that was investigated and the clinical setting, so it is essentially impossible to draw conclusions on the epidemiology, pathogenicity, and relative importance of HCoV-NH in relation to other respiratory viruses. Evidence of a novel human coronavirus that is associated with respiratory tract disease in infants and young children
cord-017161-lcqrd4v0	2012	Apart from relatively common vasculitides such as Henoch-Schönlein Purpura (HSP) and Kawasaki disease (KD), most of the primary vasculitic syndromes are rare in childhood, but when present are associated with signi fi cant morbidity and mortality [ 2, 3 ] . This chapter summarizes the fi ndings of recent studies relating to the pathogenesis of systemic vasculitis, and considers HSP, KD, antineutrophil cytoplasmic antibodies (ANCAs)-associated vasculitis, polyarteritis nodosa and Takayasu arteritis (TA). The common features between this murine model and the human disease include an infectious trigger leading to immune activation; disease susceptibility in the young; a time course similar to that seen clinically in KD; similar pathology of coronary arteritis; and response to intravenous immunoglobulin (IVIG) treatment [ 55 ] . Additional data TNF-a -308A associated with increased intravenous immune globulin (IVIG) resistance [ 82 ] Interleukin-10 (IL10) IL-10 gene promoter polymorphisms in fl uence risk of CAA [ 82 ] Vascular endothelial growth factor (VEGF) and its receptor (KDR)
cord-017245-kxqh32ip	2016	Initially described in 1967 by Dr. Tomisaku Kawasaki in Japanese children as an acute mucocutaneous lymph node syndrome [ 1 -3 ] , KD may lead to coronary artery abnormalities (CAAs) in up to 25 % of patients if left untreated. Japan reports the highest incidence of KD in the world -the present fi gure being 265/100,000 children below the age of 5 years. In the years to come, KD may soon replace rheumatic fever to become the leading cause of acquired heart disease in children in India, just as in Japan, Europe and North America. If a child has fever for less than 5 days or has less than four criteria, the presence of coronary artery abnormalities (CAAs) detected on 2D echocardiography would also suggest a diagnosis of KD [ 17 ] . A replication study for association of ITPKC and CASP3 two-locus analysis in IVIG unresponsiveness and coronary artery lesion in Kawasaki disease
cord-018638-4pyjhpbk	2019	Acute non-purulent cervical lymphadenopathy Table 4 .2 AHA 2017 diagnostic criteria for KD [28] Diagnosis of classic KD can be proffered in the presence of fever for at least 5 days associated with at least 4 of the 5 following principal clinical features. Cervical lymphadenopathy (>1.5 cm diameter), usually unilateral A careful history may reveal that ≥1 principal clinical features were present during the illness but resolved by the time of presentation Exclusion of other diseases with similar findings (e.g., scarlet fever, viral infections like measles, adenovirus, enterovirus, Stevens-Johnson syndrome, toxic shock syndrome, drug hypersensitivity reactions, systemic juvenile idiopathic arthritis) unusual for KD. Perianal desquamation is virtually pathognomonic of KD and is a useful clinical sign for diagnosis of the disease during the acute phase ( Fig. 4 .3c). Epidemiological and clinical characteristics of Kawasaki disease and factors associated with coronary artery abnormalities in East China: nine years experience
cord-024189-t7mbsr25	2008	
cord-027870-cuvfy4pj	2020	Other annular erythemas known to be a manifestation of well-defi ned diseases (e.g. neonatal lupus) or with distinctive clinical or histologic features (e.g. erythema multiforme, erythema chronicum migrans, erythema marginatum rheumaticum, and erythema gyratum repens) are not considered under this heading. Differential diagnosis includes other eruptions with ringlike lesions, such as neonatal lupus, erythema multiforme, urticaria, urticarial lesions of pemphigoid, fungal infections, erythema chronicum migrans, and congenital Lyme disease. [98] [99] [100] This type of reaction may be seen in infants with an unknown or presumably viral etiology ( Fig. 19-9) Hypersensitivity syndrome reaction is a serious drug reaction characterized by fever, skin rash, lymphadenopathy, and internal organ involvement, especially of the liver. Sweet syndrome, or acute febrile neutrophilic dermatosis, is a benign disease characterized by tender, raised erythematous plaques, fever, peripheral leukocytosis, histologic fi ndings of a dense dermal infi ltrate of polymorphonuclear leukocytes, and a rapid response to systemic corticosteroids. 412 Congenital erythropoietic porphyria and transient elevated porphyrin levels in neonates with hemolytic disease may also cause photosensitivity.
cord-030192-ebsh62ll	2020	12 Furthermore, emerging new evidence suggests that COVID-19 infection in children and adolescents is associated with a multisystem inflammatory syndrome (MIS-C), with features similar to Kawasaki disease and toxic shock syndrome, frequently requiring intensive care unit (ICU) admissions. The United States CDC has presented the following case definition for a diagnosis of MIS-C associated with COVID-19, with pediatric patients required to meet all three of the following criteria: (1.) Individual under 21 years of age presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (≥2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurologic); (2.) No alternative plausible diagnosis; (3.) Positive current or recent SARS-CoV-2 infection by RT-PCR, serology, or I n p r e s s antigen test; or COVID-19 exposure within four weeks prior to symptom onset.
cord-253056-765rs3e7	2018	title: Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection Children with persistent or recurrent fever 36 hours after the end of intravenous immunoglobulin (IVIG) are considered to be resistant to treatment and are at increased risk for coronary complications. RESULTS: Children with concomitant infection were more likely to have fever 48 hours after initial IVIG treatment (36% vs 20%, p = 0.05) and to be treated with a second dose (33% vs 18%, p = 0.04). Children with concurrent infection had higher rates of IVIG resistance (19 (33%) versus 17 (18%) patients, p = 0.04), and higher temperature at 48 hours (Fig 1) . In this retrospective series, the presence of a concomitant infection was associated with a higher rate of resistance to IVIG treatment. In this study, patients with concomitant infection had a higher rate of resistance to IVIG treatment.
cord-256642-payjduek	2019	BACKGROUND: Reactivation of the Bacillus Calmette-Guérin (BCG), manifesting as erythema, induration, ulceration or crust formation at a previous BCG inoculation site, is a common and highly specific feature of Kawasaki disease (KD). CONCLUSIONS: This case report highlights the rare finding of BCG reactivation in a child with confirmed measles infection, and suggests that this clinical manifestation may occasionally occur in children with infections or conditions other than KD. Reactivation of the BCG, manifesting as erythema, induration, ulceration or crust formation at the BCG site months or years after inoculation, has been described as an important feature of Kawasaki disease (KD) [5, 6] . Here, we present a case report of a 7-month old infant with laboratory-confirmed measles who presented with erythema and induration at the BCG inoculation site. Apart from those to confirm the measles infection, no laboratory investigations were undertaken to determine if additional viral pathogens were present in the patient and contributed to the development of the BCG reactivation.
cord-259996-uhrhsrky	2015	Coronary artery diameter, C-reactive protein levels, platelet count, alanine aminotransferase levels, and NT-pro BNP levels were significantly higher and albumin levels lower in group 2 compared with group 3. Laboratory data obtained from each patient included complete blood count, erythrocyte sedimentation rate (ESR), and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total protein, albumin, C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP). The KD patients in their studies had significantly higher positive rates for virus isolation and PCR for those viruses compared with the control group (50.4% vs. 12) found that children with KD who had respiratory virus infections had a higher incidence of coronary artery dilatation than KD patients without viral infections, and the former group were more often diagnosed with incomplete KD. Detection rate and clinical impact of respiratory viruses in children with Kawasaki disease
cord-261058-yu2qw02l	2005	Thus in genetically susceptible children, acute infections such as those causing fever and rash, may result in unrecognised damage to the cardiovascular system that later manifests itself as adult cardiovascular disease. 3 The consensus view is that KD results from a widely distributed infectious agent (or possibly agents) that causes the clinical syndrome in genetically susceptible children. Kawasaki disease is more common in boys (male:female ratio 1.6:1) 1 a feature observed in many infectious diseases 30, 31 and also in coronary atherosclerosis, where sex differences in immune responses are suggested to mediate susceptibility. A recent report of an association between the presence of genetic material from a novel coronavirus and Kawasaki disease in a handful of cases 48 remains unproven and may reflect an epiphenomenon; the putative etiological agent is a relatively common viral pathogen in young children and it is unclear how long the DNA persists.
cord-269170-9f460xbq	2020	The disease seems to result from the interplay of genetic and environmental susceptibility factors with infectious triggers, followed by a subsequent abnormal immune response characterized by increased levels of inflammatory cytokines and chemokines during the acute phase. Recent advances in culture-independent techniques for detection and identification of intestinal commensal bacteria enabled the discovery that Th17 and Treg differentiation are regulated by short chain fatty acids (SCFAs), in particular butyrate, produced by the gut microbiota. This perspective is illustrated in Figure 1 and can be explained as follows: [1] various factors during the in utero and postnatal period drive dysbiosis in young children; [2] dysbiosis results in reduced intestinal production of SCFAs including butyrate; [3] reduced levels of SCFAs in the gut cause an imbalance of Th17s/Tregs; and [4] individuals with Th17/Treg imbalances develop hypercytokinemia triggered by ubiquitous infectious agents(s), followed by KD (Figure 1) .
cord-270035-1e1wzdri	2020	The association of Kawasaki disease and COVID-19 infection has to our knowledge been reported only once (5), we report a second case from Italy, currently the third most affected country in the world with regard to number of proven SARS-COV-2 infections. We were then contacted as reference Center for Kawasaki Disease (KD) in our Pediatric Immunology Unit: considering the clinical history (fever lasting more than 5 days, erythematous rash, labial, and conjunctival hyperemia) and the result of laboratory tests we confirmed the diagnostic suspicion of atypical/incomplete KD without coronary involvement, and started treatment with high dose intravenous immunoglobulins (IVIG) 2 g/kg and high dose acetylsalicylic acid (ASA 50 mg/kg/day). In the setting of COVID-19 there are several reports of using corticosteroids for Acute Respiratory Disease Syndrome (ARDS), but considering the not severe clinical course and presentation in our patient we did not start steroid therapy.
cord-277908-d26xzean	2020	Early-childhood prescribed antibiotics associated with type 1 Diabetes Main Results 1,297 children (0.2%) developed DM1 (median age 4.0 years, range 0-8.3). Conclusions Early-life prescribed antibiotics for otitis media and respiratory infections, are associated with DM1 development, with a higher risk in cesarean delivery birth. Those diagnosed in the COVID-19 era demonstrated a higher incidence: 10 vs 0.3 per month, mean age: 7.5 vs 3.0 years, Kawasaki disease shock syndrome: 50% vs 0%, MAS: 50% vs 0%, and steroid requirement: 80% vs 15%, all P < .01. Emphasizing, at health supervision visits, the American Academy of Pediatrics recommendations regarding appropriate media use with children, 3 parents should also be apprised of the association between earlier screen exposure and the risk of developing ASD-like symptoms, although currently, a causal relationship cannot be inferred. 1 US studies based on vital statistics data, found a higher risk of neonatal death in home compared with hospital births.
cord-278761-cqrggpmj	2020	title: Sars-CoV-2 et Kawasaki, rapprochement à risque Focus © zilvergolf/stock.adobe.com Le Lancet a publié une observation, d''une équipe de pédiatrie de l''hôpital Pape-Jean-XXIII de Bergame [1] , évoquant ce Kawasaki-like sévère avec l''épidémie de Covid-19. Les médecins ont évalué les caractéristiques cliniques d e s p a t i e n t s K a w a s a k i -l i k e lors de l''épidémie, ilsont repris les obser vations de maladie de Kawasaki des cinq dernières années au service de pédiatrie, selon un groupe 1 (avant le Covid-19) et un groupe 2 (après le début du Covid-19). La présentation de Kawasaki-like a été comparée à la maladie de Kawasaki selon les critères de l''American Heart Des cliniciens français ont récemment établi un rapprochement entre le Covid-19 et la maladie de Kawasaki chez l''enfant très symptomatique porteur du Sars-CoV-2, à type de Kawasaki-like. Sars-CoV-2 et Kawasaki, rapprochement à risque .
cord-280280-9jr7ekbu	2020	Ongoing studies and accumulated data are detailing the features and the effects of the new coronavirus disease 19 (COVID 19) in the adult population, and cardiovascular involvement is emerging as the most significant and life-threatening complication, with an increased risk of morbidity and mortality in patients with underlying cardiovascular disease. At present, though the limited data on the effects of COVID 19 in pediatric patients, children seem to count for a little proportion of SARS-COV 2 infection, and present with less severe disease and effects However infants and toddlers are at risk of developing critical course. Coronavirus disease 19 (COVID-19) is a severe acute respiratory syndrome for which the etiologic agent is the novel beta coronavirus SARS-CoV-2, first described in December 2019 in China in a cluster of patients presenting with pneumonia. The main presenting clinical feature of the disease is pneumonia, ranging from asymptomatic or mildly symptomatic to severe acute respiratory distress syndrome, but cardiovascular involvement is emerging as one of the most significant and life-threatening complications of SARS-CoV-2 infection (1, 2) .
cord-283349-9x2d1qip	2020	title: Peripheral blood smears of children with multisystem inflammatory syndrome demonstrate prominence of early myeloid forms with morphologic evidence of toxic change There is a growing body of evidence that suggests that children have largely been spared of much of the morbidity associated with the ongoing SARS-CoV-2 pandemic 1,2 Over the last several weeks, however, there has been an increasing awareness and understanding of a hyperinflammatory shock syndrome that appears to mimic some aspects of Kawasaki disease in some pediatric patients. While the role that neutrophils play in the development of Kawasaki disease continues to be clarified, it is described in the literature that higher neutrophil to lymphocyte ratios (NLRs) may portend an increased risk of resistance to treatment with intravenous immunoglobulin as well as development of coronary aneurysms 6, 7 Indeed, there is also evidence that suggests that higher NLRs in patients with COVID-19 are associated with increased levels of inflammation and clinical severity.
cord-286607-5i406twr	2019	Kawasaki syndrome (KS) is a necrotizing vasculitis of smalland medium-sized vessels mostly affecting children under 5 years of age; a host of clinical and epidemiological data supports the notion that KS might result from an infectious disease. All studies available to date have confirmed that an imbalance in the gut microbiota might indirectly interfere with the normal function of innate and adaptive immunity, and that variable microbiota interactions with environmental factors, mainly infectious agents, might selectively drive the development of KS in genetically susceptible children. The microbiota, a microbial community of trillions of microorganisms and at least 1,000 different bacterial species, some eukaryotic fungi and viruses, and which covers every surface of the human body, plays a contributory role in many infections, immune-mediated disorders, rheumatologic diseases, and disorders of the nervous system.
cord-292719-n5lg43tr	2014	To investigate the infectious etiology of Kawasaki disease, we initiated a prospective case-control study to investigate possible links between common viral infections and Kawasaki disease. The infectious evidence of Kawasaki disease includes temporal clustering and marked seasonality, geographic clustering, family clustering, a high association between Kawasaki disease and infectious disease surveillance, and age distribution, for which the highest incidence rates are seen among 6 monthe2-year-old children who have low maternal antibodies and are most susceptible to infections in general. We thus carried out a prospective case-control study to investigate the association of common viral infections with Kawasaki disease to test the above hypothesis. We enrolled Kawasaki disease cases that had fever for over 5 days and at least four of the following five manifestations: neck lymphadenopathy, lip fissure and/or strawberry tongue, skin rash, nonpurulent bulbar conjunctivitis, palm/sole erythema, and induration followed by periungual desquamation. The c 2 test was used to compare the rates of viral isolation and PCR of various viruses between KD cases and the control children.
cord-293714-s6ezxi5r	2013	Further findings that strongly support an infectious origin of KS are those of Orenstein et al., who used light microscopy and TEM to study tissue specimens from 32 autopsies, eight heart transplants and an excised coronary aneurysm of patients with KS and identified three different vasculopathic processes: acute self-limited necrotising arteritis (NA), subacute/chronic vasculitis, and luminal myofibroplastic proliferation. More recently, Japanese and Taiwanese groups independently reported a significant association between KS and polymorphisms in the intergenic region on chromosome 8p23-p22 between B lymphoid kinase (BLK ), a tyrosine kinase involved in B-cell receptor signal transduction and FAM167A, a functionally uncharacterized gene. 117 They found that polymorphisms at BLK gene together with genetic abnormalities at CD40, were associated with KS at genomewide significance (p < 5.5 Â 10 À8 ) confirming the role of immune activation and inflammation in the pathogenesis of the syndrome. Association of vascular endothelial growth factor (VEGF) and VEGF receptor gene polymorphisms with coronary artery lesions of Kawasaki disease
cord-294729-c9f0iokr	2020	Conclusion: Our representative case of a patient with coronavirus disease-19-associated multisystem inflammatory syndrome in children without robust hyperinflammation and a delayed finding of coronary artery dilatation compared with reported case series highlights the need for further mechanistic understanding of coronavirus disease-19 disease and subsequent multisystem inflammatory syndrome in children or Kawasaki disease development. Key Words: coronavirus disease-19; immune suppression; Kawasaki disease; multisystem inflammatory syndrome in children; research S ignificant disease burden in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been relatively uncommon in children with less than 5% of cases in the United States and globally under 18 years old (1) (2) (3) (4) (5) (6) . However, although children appear to have a less severe acute disease course, worldwide cases of a postinfectious multisystem inflammatory syndrome in children (MIS-C) and possible atypical Kawasaki-like disease attributed to SARS-CoV-2 infection have arisen (8) (9) (10) .
cord-299870-4ulmbn1r	2020	Intravenous immunoglobulin (IVIG) in association with aspirin represents the main treatment for KD, and administration of these treatments within the first 10 days following fever onset has been associated with a fivefold reduction in the risk of coronary artery aneurysms (CAA) [1] . The first report on the use of anti-IL-1 in KD dates back to 2012 [20] and described a 2-year-old boy with classic KD who developed myocarditis with reduction of the ejection fraction to 20%, without coronary artery inflammation, 2 days after the first dose of IVIG. The main reason for the use of anakinra was persistent fever (8/11), followed by gradual dilatation of the coronary arteries (7/11), persistence of clinical (2/11) or laboratory abnormalities (6/11), and severe myocarditis with KD shock syndrome in one case. This study supports the early use of anakinra in cases refractory to IVIG, demonstrating that it is quickly effective on KD symptoms, inflammation parameters, and dilatation of the coronary arteries in most patients, with good tolerability.
cord-300216-3mvfiuwc	2020	title: Subconjunctival Acute Bilateral Hemorrhages Due to Kawasaki Disease in a Costa Rican Girl: An Unusual Clinical Manifestation of the Disease Among the ocular manifestations in these patients, bilateral non-suppurative conjunctival injection and uveitis are the most common. We describe a six-year-old Costa Rican girl with acute Kawasaki disease who developed severe bilateral conjunctival injection with subsequent bilateral subconjunctival hemorrhages. To our knowledge, this is the first report from Latin America and among the few in the literature of a child in whom severe bilateral subconjunctival hemorrhages occur as a manifestation of Kawasaki disease. Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired cardiac disease in children, with approximately 80% of cases occurring in children in the first five years of age. Rare ocular manifestations in an 11-year-old girl with incomplete Kawasaki disease: a case report
cord-301107-0njnjqeb	2020	After pandemic, the number of patients with Pityriasis rosea and Kawasaki disease increased significantly in patients who applied to the dermatology outpatient clinic. Herein, we wanted to aim to evaluate whether two diseases (Pityriasis rosea and Kawasaki disease), in which Human Herpesvirus 6 (HHV-6) was held responsible for etiopathogenesis, after the COVID-19 pandemic. After pandemic, the number of patients with Pityriasis rosea increased significantly in patients who applied to the dermatology outpatient clinic (p:0,000). After pandemic, the number of patients with Kawasaki disease increased significantly in patients who applied to the dermatology outpatient clinic (p:0,009). In our study, it was found that the rate of Pityriasis rosae patients who applied to the dermatology outpatient clinic this year during the pandemic period increased approximately 5 times compared to the same time last year. In our study, there was a 10-fold increase in the rate of patients with Kawasaki disease who applied to the dermatology outpatient clinic compared to the previous year.
cord-301160-7ik3iszp	2012	Therefore, circulating immune cells, especially T cells, control the inflammation of the majority of the affected regions of KD patients without sequelae, but they also may be involved in the progression of the disease, such as in the case of CALs. Epidemiological and clinical data suggest that KD is an immunological reaction to infectious triggers occurring in genetically susceptible children. Many genetic studies in different countries have evaluated variants in candidate KD genes, and a number of variants, including inositol 1,4,5 triphosphate 3-kinase (ITPKC) and caspase-3, risk of CALs. For example, a severely affected patient who is persistently febrile for a week, showing constant low levels of platelet with high levels of AST and ALT in followup examination, may still not have reached the peak stage of inflammation, suggesting a higher possibility of more severe CALs. Laboratory findings are now mandatory for diagnosis of incomplete KD.
cord-304533-qwbbsg14	2020	key: cord-304533-qwbbsg14 cord_uid: qwbbsg14 The patient had no previous his tory of COVID19 symptoms or con tact with known COVID19 cases. Adult and paediatric specialists conferred and concluded that the most likely diagnosis was Kawasaki like disease on the PIMSTS spectrum. Kawasaki dis ease has been described in adults in association with viral infection. 4, 5 To the best of our knowledge, this is the first reported case of adult Kawasaki like disease related to SARSCoV2 infection. There is an urgent need to recognise and fully characterise PIMS TS in young adults to improve our understanding of pathogenesis, guide treatment decisions, and prevent sequelae in these patients. An outbreak of severe Kawasakilike disease at the Italian epicentre of SARSCoV2 epidemic: an observational cohort study A case of complete adultonset Kawasaki disease: a review of pathogenesis and classification Kawasakilike syndromes in HIVinfected adults
cord-309317-cgs0sui7	2020	Emerging reports show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection precedes the appearance of various autoimmune and autoinflammatory diseases, including paediatric inflammatory multisystemic syndrome (PIMS) or multisystem inflammatory syndrome in children (MIS-C), thus adding to the growing mystery of this virus and raising questions about the nature of its link with autoimmune and autoinflammatory sequelae. Several emerging reports show that coronavirus disease 2019 (COVID-19), a pandemic respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), could lead to autoimmune and autoinflammatory diseases, such as paedi atric inflammatory multisystemic syndrome (PIMS; which includes Kawasaki-like disease, Kawasaki disease shock syndrome, toxic shock syndrome, myocarditis and macrophage activation syndrome) in children [1] [2] [3] [4] [5] [6] . In the USA, the New York City Health Department on 4 May 2020 reported that 15 children aged 2-15 years had presented with symptoms of MIS-C, including persistent fever and increased levels of inflammatory markers, and many also had rash, abdominal pain, vomiting or diarrhea; ten of the 15 child ren were positive for SARS-CoV-2 infection 6 .
cord-312486-rumqopg0	2020	The question is whether ACE2 expression levels are pertinent to SARS-CoV-2 infection only in the tissues relevant to viral entry and the lungs as its major target, [44, 45] or, given that COVID-19 in its severe form is a systemic disease with multi-organ disfunction [46, 47] , ACE2 expression levels may be important in multiple organs and tissues other than those of the respiratory system. However, the activation of multiple complement pathways, dysregulated neutrophil responses, endothelial injury, and hypercoagulability appear to be interlinked with SARS-CoV-2 infection and instead serve to drive the severity of the disease [91] . Regarding SLE, the prototypic systemic autoimmune disease, a group of investigators suggested that inherent epigenetic dysregulation causing hypomethylation and overexpression of ACE2, the functional receptor for SARS-CoV-2, might facilitate viral J o u r n a l P r e -p r o o f entry, viremia, and increased likelihood of cytokine storm in such patients [153] .
cord-314662-nem6dw34	2020	Initial reports surfaced in the UK [3] and Italy [4] , followed by New York and other parts of the U.S. Preliminary accounts of the features of this syndrome resemble those of known entities such as Kawasaki Disease (KD), toxic shock syndrome (TSS), and secondary hemophagocytic lymphohistiocytosis (SHLH)/macrophage activation syndrome (MAS). Early consultation of specialists to assist in management, such as intensive care, cardiology, rheumatology, infectious diseases, allergy/immunology, neurology Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; pro-BNP, pro-B-type natriuretic peptide; BUN, blood urea nitrogen; CRP, C-reactive protein; CT, computed tomography; ESR, erythrocyte sedimentation rate; GI, gastrointestinal; HLH, hemophagocytic lymphohistiocytosis; IL, interleukin; MIS-C, multisystem inflammatory syndrome in children; NK, natural killer; NP, nasopharyngeal; PT, prothrombin time; PTT, partial thromboplastin time; RT-PCR, reverse transcriptase polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
cord-315001-1ui27pkc	2020	Due to her prolonged fever, she was tested for COVID-19 which was positive; however, she did not develop respiratory symptoms during her illness. At the time of manuscript submission, this is the second case report to our knowledge showing an association between Kawasaki Disease and SARS-CoV-2 virus, both of which are poorly understood diseases in the pediatric population. This case highlights the value of testing pediatric patients for COVID-19 who present with fever in the absence of other symptoms to improve epidemiologic measures during the ongoing pandemic, and it also adds to a foundation of cases for future research on the presence of a link between Kawasaki Disease and COVID-19. We present a case showing an association between Kawasaki disease and the SARS-CoV-2 virus. is case highlights the value of testing patients for COVID-19 during evaluation for Kawasaki disease (KD). is case highlights the value of testing patients for COVID-19 during evaluation for possible Kawasaki disease.
cord-323202-kcy8xoos	2020	The observed and synthetic KD clusters were compared with respect to demographic and clinical characteristics and median values for standard laboratory data using univariate analysis and a multivariate, Rotated Empirical Orthogonal Function Analysis (REOFs). CONCLUSIONS: Cases of Kawasaki disease within a cluster were more similar with respect to demographic and clinical features, and levels of inflammation than would be expected by chance. In the univariate analysis, cluster-level averages of demographic and clinical characteristics were compared between the set of 47 true KD clusters and 100 sets of 47 synthetic clusters of equal size created either by randomly shuffling membership of cluster cases (referred to as shuffled clusters) or by randomly creating clusters from non-cluster cases of Kawasaki disease within the same season as the true cluster (referred to as control clusters). (Figure 2 ; available at www.jpeds.com) Striking differences were noted between individual true clusters and synthetic clusters for the following variables: age, ESR, and the presence of enlarged lymph nodes or strawberry tongue.
cord-331249-jrzgqq8q	2006	Para que un caso pueda ser diagnosticado de enfermedad de Kawasaki incompleta, debe tener al menos 5 días de fiebre, 2 o 3 criterios clínicos, elevación de los reactantes de fase aguda (proteína C reactiva y/o velocidad de sedimentación) y al menos 3 de las siguientes alteraciones analíticas: albúmina ≤ 3 g/dl, anemia para la edad del niño, elevación de alaninaminotransferasa, plaquetas > 450.000 después de 7 días de fiebre, leucocitos ≥ 15.000/µl y en orina ≥ 10 células/campo. Hay autores que incluso proponen un tratamiento si el niño es un lactante con fiebre sin foco de más de 5 días de duración, acompañada de aumento de la proteína C reactiva, neutrofilia y trombocitosis después de 7 días de fiebre, pero muy especialmente si tiene al menos uno de los siguientes signos: inyección conjuntival, enrojecimiento de labios o exantema 48 .
cord-333145-a20dlaxn	2020	In a meta-analysis of three GWAS for susceptibility to Kawasaki disease (KD) conducted in Japan, Korea, and Taiwan and follow-up studies with a total of 11,265 subjects (3428 cases and 7837 controls), a significantly associated SNV in the immunoglobulin heavy variable gene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P = 6.0 × 10(−9)). Considering that significant association of SNVs in the IGHV region with disease susceptibility was previously known only for rheumatic heart disease (RHD), a complication of acute rheumatic fever (ARF), these observations suggest that common B-cell related mechanisms may mediate the symptomology of KD and ARF as well as RHD. Instead, 7 out of 12 groups of SNVs in the 6p21 region examined in the Stage 2 analyses showed significant association in the metaanalyses of the data sets in the three GWAS as well as in the follow-up studies ( Table 1 and Supplementary Fig. 3A ).
cord-342372-2g9sq36w	2016	The use of corticosteroids in patients with KD is currently reserved for children who have received ≥2 infusions of IVIG on the basis that effects of steroid therapy on coronary artery abnormalities were uncertain at the time of publication of KD treatment guidelines in 2004. In Japan, the study on the efficacy of IVIG and steroids in patients with severe presentation of KD (RAISE study), a multicenter, prospective, randomized, open-label, blinded-endpoints trial, showed combination treatment with IVIG and prednisolone had significant advantages over IVIG alone in the prevention of coronary artery abnormalities with rapid defervescence of fever and normalization of inflammatory markers [41•] . The earlier initiation of IVIG and corticosteroid therapy with subsequent increased steroid treatment duration was associated with significantly lower rates of coronary artery abnormalities in the RAISE study. Treatment with infliximab in patients with refractory Kawasaki disease was associated with shorter duration of fever and hospitalization when compared to second dose of IVIG in this randomized
cord-343387-7el80yby	2020	Recent reports have described in the pediatric population a new type of hyperinflammatory response manifested following contact with SARS-CoV-2, with some of the clinical features attributable to Kawasaki disease (KD). Although today little is known about the etiology of KD, the most accepted hypothesis is that of a probable viral etiology, therefore, even the SARS-CoV-2 virus could trigger, in genetically predisposed subjects, an exaggerated inflammatory response that is clinically evident like the one described in KD. In this context the scientific community is wondering about a possible correlation between SARS-CoV-2 virus infection and the onset of Kawasaki-like diseases. They suggest that this clinical picture represents a new phenomenon that affects previously asymptomatic children with SARS-CoV-2 infection manifesting itself as a hyperinflammatory multi-organ involvement syndrome similar to a shock syndrome in KD [8] . Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study
cord-353229-k3zerr83	2020	Herein, we report the characteristics of four patients with Kawasaki-like phenotype associated with COVID-19 from Turkey and analyze the features of similar published cases through a systematic literature review. Diagnosis of complete KD was based on the criteria of the American Heart Association (AHA): the presence of fever for at least 5 days accompanied by the presence of at least four of the following five findings: bilateral non-exudative conjunctival injection, unilateral cervical lymphadenopathy, changes in the lips and oral cavity, skin rash, and changes in extremities, including indurative angioedema and desquamation [18] . Children with persistent fever, inflammation (neutrophilia, high CRP, and lymphopenia), and single or multi-organ dysfunction have been identified in the UK as "Pediatric Multisystem Inflammatory Syndrome in relation to SARSCoV-2 (PMIS-TS)" regardless of the SARS-CoV-2 RT-PCR test results [73] . Pediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort