Exploring viral infections' role in Kawasaki disease onset: A study during the COVID-19 pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, known viral diseases declined in all ages. By using the current situation as a natural experiment, this study aimed to evaluate whether the change in the incidence of Kawasaki disease (KD) during the COVID-19 pandemic varies with age and whether a specific infectious disease mediates the occurrence of KD. Monthly number of KD patients were extracted from the nationwide inpatient database. Segmented regression analysis was conducted on the interrupted time series data. Additionally, causal mediation analysis was performed to examine the role of viral infections in the changes in the number of KD patients. After the first emergency declaration for COVID-19 in Japan, there was an immediate decrease in the number of KD patients per 100 000 population aged between 6 months and 4 years (immediate change = -2.66; 95% confidence interval [CI]: -5.16 to -0.16) and aged 5-15 years (immediate change = -0.26; 95% CI: -0.49 to -0.04). However, no immediate change was observed in patients under 6 months of age. In the causal mediation analysis for each viral infection, it was found that the decrease in the number of patients with KD was mediated by changes in the number of patients with pharyngoconjunctival fever and infectious gastroenteritis. The current results suggest that viral infections may be one of the etiological agents for KD, while they may not be the main cause in early infancy. Specifically, we found that adenovirus infection and gastroenteritis was closely related to the onset of KD in some areas of Japan.

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.

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.).

Identification of Torquetenovirus Species in Patients with Kawasaki Disease Using a Newly Developed Species-Specific PCR Method.

A next-generation sequencing (NGS) study identified a very high viral load of Torquetenovirus (TTV) in KD patients. We aimed to evaluate the feasibility of a newly developed quantitative species-specific TTV-PCR (ssTTV-PCR) method to identify the etiology of KD. We applied ssTTV-PCR to samples collected from 11 KD patients and 22 matched control subjects who participated in our previous prospective study. We used the NGS dataset from the previous study to validate ssTTV-PCR. The TTV loads in whole blood and nasopharyngeal aspirates correlated highly (Spearman's R = 0.8931, p < 0.0001, n = 33), supporting the validity of ssTTV-PCR. The ssTTV-PCR and NGS results were largely consistent. However, inconsistencies occurred when ssTTV-PCR was more sensitive than NGS, when the PCR primer sequences mismatched the viral sequences in the participants, and when the NGS quality score was low. Interpretation of NGS requires complex procedures. ssTTV-PCR is more sensitive than NGS but may fail to detect a fast-evolving TTV species. It would be prudent to update primer sets using NGS data. With this precaution, ssTTV-PCR can be used reliably in a future large-scale etiological study for KD.

Coronavirus disease 2019 (COVID-19): A systematic review of 133 Children that presented with Kawasaki-like multisystem inflammatory syndrome.

Kawasaki-like disease (KLD) and multisystem inflammatory syndrome in children (MIS-C) are considered as challenges for pediatric patients under the age of 18 infected with coronavirus disease 2019 (COVID-19). A systematic search was performed on July 2, 2020, and updated on December 1, 2020, to identify studies on KLD/MIS-C associated with COVID-19. The databases of Scopus, PubMed, Web of Science, Embase, and Scholar were searched. The hospitalized children with a presentation of Kawasaki disease (KD), KLD, MIS-C, or inflammatory shock syndromes were included. A total number of 133 children in 45 studies were reviewed. A total of 74 (55.6%) cases had been admitted to pediatric intensive care units (PICUs). Also, 49 (36.8%) patients had required respiratory support, of whom 31 (23.3%) cases had required mechanical ventilation/intubation, 18 (13.5%) cases had required other oxygen therapies. In total, 79 (59.4%) cases had been discharged from hospitals, 3 (2.2%) had been readmitted, 9 (6.7%) had been hospitalized at the time of the study, and 9 (6.7%) patients had expired due to the severe heart failure, shock, brain infarction. Similar outcomes had not been reported in other patients. Approximately two-thirds of the children with KLD associated with COVID-19 had been admitted to PICUs, around one-fourth of them had required mechanical ventilation/intubation, and even some of them had been required readmissions. Therefore, physicians are strongly recommended to monitor children that present with the characteristics of KD during the pandemic as they can be the dominant manifestations in children with COVID-19.

Shock and Myocardial Injury in Children With Multisystem Inflammatory Syndrome Associated With SARS-CoV-2 Infection: What We Know. Case Series and Review of the Literature.

BACKGROUND: Multisystem inflammatory syndrome associated with SARS-CoV-2 infection can lead to myocardial injury and shock in children, likely the result of a severe inflammatory state, and can mimic Kawasaki disease. OBJECTIVE: To describe the characteristics of shock and myocardial injury in children with confirmed or suspeted COVID-19 during the SARS-CoV-2 pandemic in Spain, including clinical presentation, laboratory and imaging findings, treatment, disease course, and outcome. An extensive literature review is provided. METHODS: Retrospective case series including all children (age 1 month-18 years) admitted to a pediatric intensive care unit in Madrid, Spain, between March 15 and April 30, 2020 with suspected or confirmed SARS-CoV-2 infection and shock. RESULTS: Twelve previously healthy patients with shock, age 5 to 14 years, were included. All required volume resuscitation and 75% required vasoactive/inotropic support. Distributive shock was present on admission in 67% (n = 8), and 4 patients (33%) showed features of cardiogenic shock. Myocardial injury was diagnosed in 67% (n = 8) and ventricular dysfunction in 33% (n = 4). The most common symptoms on presentation were fever (100%), anorexia (100%), diarrhea (75%), and vomiting (75%). Five patients showed signs of Kawasaki disease but none met the criteria for the classic form. Laboratory findings revealed lymphopenia (83%), thrombocytopenia (83%), and increased inflammatory markers (100%). Respiratory status was not significantly impacted. Chest X-ray showed bilateral alveolar infiltrates in 7 (58%) and bilateral pneumonia in 3 (25%). COVID-19 was confirmed in 11 cases (92%). All received empirical therapy against COVID-19, thromboprophylaxis and immunomodulation. Median stay in the PICU and inpatient ward was 4.5 and 10 days, respectively. No patients died. CONCLUSION: Multisystem inflammatory syndrome in children with COVID-19 can mimic Kawasaki disease and lead to a combination of distributive and cardiogenic shock, probably secondary to a hyperinflammatory state that remains to be precisely defined. Treatment strategies include hemodynamic support, empirical therapies against COVID-19, thromboprophylaxis, and immunomodulation.

Paediatric multisystem inflammatory syndrome associated with COVID-19: filling the gap between myocarditis and Kawasaki?

Myocarditis and Kawasaki disease are common but usually distinct diseases in children. During the coronavirus pandemic (COVID-19), reports of a new form of myocarditis with clinical features of Kawasaki appeared. We investigated the place of this new disease in the spectrum encompassing Kawasaki disease and myocarditis.Thirty two consecutive children referred to our centre for a suspicion of Kawasaki or a diagnosis of myocarditis were included and eventually divided into four groups: 11 Kawasaki diseases, 6 Kawasaki syndromes (children with another diagnosis), 7 myocarditis without Kawasaki clinical feature and 7 myocarditis with incomplete Kawasaki clinical features. All were treated with immunoglobulins except those of the myocarditis group. The survival rate was 91%. The 7 children with myocarditis and clinical features of incomplete Kawasaki were all positive for SARS-CoV-2. They had a transient myocardial failure with a favourable course and none had coronary artery disease.Conclusion: Every COVID-19 child within our population had a mild to severe myocarditis and presented with fever plus two or three Kawasaki clinical features. Short-term evolution was good for these children. This new disease seems to fill the gap between isolated myocarditis and Kawasaki disease. What is Known: • A new paediatric disease close to Kawasaki disease appeared during the COVID-19 pandemic What is New: • In our population, children presented with fever, vivid Kawasaki clinical features (although the Kawasaki syndrome was always incomplete) and a myocarditis without coronary abnormalities. • The new disease fills the gap between paediatric myocarditis and Kawasaki disease but its prognosis is much better.

Skin manifestations of COVID-19 in children: Part 2.

The current COVID-19 pandemic is caused by the SARS-CoV-2 coronavirus. The initial recognized symptoms were respiratory, sometimes culminating in severe respiratory distress requiring ventilation, and causing death in a percentage of those infected. As time has passed, other symptoms have been recognized. The initial reports of cutaneous manifestations were from Italian dermatologists, probably because Italy was the first European country to be heavily affected by the pandemic. The overall clinical presentation, course and outcome of SARS-CoV-2 infection in children differ from those in adults, as do the cutaneous manifestations of childhood. In this review, we summarize the current knowledge on the cutaneous manifestations of COVID-19 in children after thorough and critical review of articles published in the literature and from the personal experience of a large panel of paediatric dermatologists in Europe. In Part 1, we discussed one of the first and most widespread cutaneous manifestations of COVID-19, chilblain-like lesions. In this part of the review, we describe other manifestations, including erythema multiforme, urticaria and Kawasaki disease-like inflammatory multisystemic syndrome. In Part 3, we discuss the histological findings of COVID-19 manifestations, and the testing and management of infected children for both COVID-19 and any other pre-existing conditions.

The Emerging Role of Neutrophils in the Pathogenesis of Thrombosis in COVID-19.

Previous studies have shown that COVID-19 leads to thrombotic complications, which have been associated with high morbidity and mortality rates. Neutrophils are the largest population of white blood cells and play a pivotal role in innate immunity. During an infection, neutrophils migrate from circulation to the infection site, contributing to killing pathogens. This mechanism is regulated by chemokines such as IL-8. Moreover, it was shown that neutrophils play an important role in thromboinflammation. Through a diverse repertoire of mechanisms, neutrophils, apart from directly killing pathogens, are able to activate the formation of thrombi. In COVID-19 patients, neutrophil activation promotes neutrophil extracellular trap (NET) formation, platelet aggregation, and cell damage. Furthermore, neutrophils participate in the pathogenesis of endothelitis. Overall, this review summarizes recent progress in research on the pathogenesis of COVID-19, highlighting the role of the prothrombotic action of neutrophils in NET formation.

Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort.

BACKGROUND: Current data suggest that COVID-19 is less frequent in children, with a milder course. However, over the past weeks, an increase in the number of children presenting to hospitals in the greater Paris region with a phenotype resembling Kawasaki disease (KD) has led to an alert by the French national health authorities. METHODS: Multicentre compilation of patients with KD in Paris region since April 2020, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ('Kawa-COVID-19'). A historical cohort of 'classical' KD served as a comparator. RESULTS: Sixteen patients were included (sex ratio=1, median age 10 years IQR (4·7 to 12.5)). SARS-CoV-2 was detected in 12 cases (69%), while a further three cases had documented recent contact with a quantitative PCR-positive individual (19%). Cardiac involvement included myocarditis in 44% (n=7). Factors prognostic for the development of severe disease (ie, requiring intensive care, n=7) were age over 5 years and ferritinaemia >1400 µg/L. Only five patients (31%) were successfully treated with a single intravenous immunoglobulin (IVIg) infusion, while 10 patients (62%) required a second line of treatment. The Kawa-COVID-19 cohort differed from a comparator group of 'classical' KD by older age at onset 10 vs 2 years (p<0.0001), lower platelet count (188 vs 383 G/L (p<0.0001)), a higher rate of myocarditis 7/16 vs 3/220 (p=0.0001) and resistance to first IVIg treatment 10/16 vs 45/220 (p=0.004). CONCLUSION: Kawa-COVID-19 likely represents a new systemic inflammatory syndrome temporally associated with SARS-CoV-2 infection in children. Further prospective international studies are necessary to confirm these findings and better understand the pathophysiology of Kawa-COVID-19. Trial registration number NCT02377245.

SARS-CoV-2, which induces COVID-19, causes kawasaki-like disease in children: role of pro-inflammatory and anti-inflammatory cytokines.

Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic coronavirus disease 2019 (COVID-19). In humans, SARS-CoV-2 infection leads to acute respiratory distress syndrome which presents edema, hemorrhage, intra-alveolar fibrin deposition, and vascular changes characterized by thrombus formation, micro-angiopathy and thrombosis. These clinical signs are mediated by pro-inflammatory cytokines. In recent studies it has been noted that COVID-19 pandemic can affect patients of all ages, including children (even if less severely) who were initially thought to be immune. Kawasaki disease is an autoimmune acute febrile inflammatory condition, which primarily affects young children. The disease can present immunodeficiency with the inability of the immune system to fight inflammatory pathogens and leads to fever, rash, alterations of the mucous membranes, conjunctiva infection, pharyngeal erythema, adenopathy, and inflammation. In the COVID-19 period, virus infection aggravates the condition of Kawasaki disease, but it has also been noted that children affected by SARS-V-2 may develop a disease similar to Kawasaki's illness. However, it is uncertain whether the virus alone can give Kawasaki disease-like forms. As in COVID-19, Kawasaki disease and its similar forms are mediated by pro-inflammatory cytokines produced by innate immunity cells such as macrophages and mast cells (MCs). In light of the above, it is therefore pertinent to think that by blocking pro-inflammatory cytokines with new anti-inflammatory cytokines, such as IL-37 and IL-38, it is possible to alleviate the symptoms of the disease and have a new available therapeutic tool. However, since Kawasaki and Kawasaki-like diseases present immunodeficiency, treatment with anti-inflammatory/immunosuppressant molecules must be applied very carefully.

The clinics of HHV-6 infection in COVID-19 pandemic: Pityriasis rosea and Kawasaki disease.

A new type of coronavirus family (SARS-CoV-2), which can be found in humans and animals, with many varieties and clinical symptoms, was first seen in Wuhan, China in late 2019, under the name novel Coronavirus Disease 2019 (COVID-19). In the literature, cutaneous symptoms related to the disease are generally emphasized. However, it is not yet known whether this new SARS-CoV-2 virus, which has entered our lives, plays a role in the etiopathogenesis of dermatological diseases. The patients who were admitted to the dermatology outpatient clinic between 1 April and 15 May 2019, and on 1 April and 15 May 2020 were retrospectively analyzed by searching the hospital automation system and patient files. The reason for the same months to be included in the study was to exclude seasonal effects on the diseases. After pandemic, the number of patients with Pityriasis rosea and Kawasaki disease increased significantly in patients who applied to the dermatology outpatient clinic. Our study is the first study showing Pityriasis rosea increase during the pandemic period. We think that this increase is related to HHV-6 reactivation. Herein, we wanted to draw attention to two diseases in which Human Herpes 6 (HHV-6) was accused in etiopathogenesis: Kawasaki disease and Pityriasis rosea.

Kawasaki-like disease in children with COVID-19.

Children with Coronavirus disease 2019 (COVID-19) are being reported to have manifestations of hyperinflammatory states and/or Kawasaki-like disease. In this study, we investigated children with typical and atypical Kawasaki disease (KD) likely to be associated with COVID-19. We have reported four children with Kawasaki-like disease probably associated with COVID-19. The clinical features were consistent with incomplete KD in three patients. SARS-CoV-2 RT-PCR was positive in one and the serology was positive in one patient with negative RT-PCR. Corticosteroids, anakinra, intravenous immunoglobulin (IVIG), and acetylsalicylic acid were used in the treatment. Three patients recovered after the treatment while one patient died. The literature review revealed 36 articles describing 320 children with Kawasaki-like disease associated with COVID-19. SARS-CoV-2 RT-PCR was negative in 120 (65.5%) of 183 patients while the serology was positive in 130 (83.8%) of 155 patients. The therapeutic options have included IVIG, acetylsalicylic acid, tocilizumab, anakinra, enoxaparin, and methylprednisolone. Pediatric COVID-19 cases may present with atypical/incomplete Kawasaki-like disease. Thus, pediatricians need to be aware of such atypical presentations resembling KD for early diagnosis of COVID-19.

Kawasaki Disease Features and Myocarditis in a Patient with COVID-19.

A 10-year-old male with prolonged fever, rash, and conjunctivitis presented to the emergency department with concern for Kawasaki disease, found to have myocarditis and PCR positive for SARS-CoV-2.

Association between SARS-CoV-2 infection and Kawasaki-like multisystem inflammatory syndrome: a retrospective matched case-control study, Paris, France, April to May 2020.

We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and Kawasaki disease (KD)-like multisystem inflammatory syndrome in a retrospective case-control study in France. RT-PCR and serological tests revealed SARS-CoV-2 infection in 17/23 cases vs 11/102 controls (matched odds ratio: 26.4; 95% confidence interval: 6.0-116.9), indicating strong association between SARS-CoV-2 infection and KD-like illness. Clinicians should keep a high level of suspicion for KD-like illness during the COVID-19 pandemic.

A viral infection explanation for Kawasaki disease in general and for COVID-19 virus-related Kawasaki disease symptoms.

SARS-CoV-2, a new virus that appeared in Wuhan, China, in 2019 has approximately an 80% genomic match to the Severe Acute Respiratory Symptom (SARS) virus, which is known to come from a bat virus. Symptoms of Kawasaki disease in general and incomplete Kawasaki disease have been seen in a subset of pediatric patients having a current or previous infection of SARS-CoV-2. A viral infection, such as a SARS-CoV-2 virus infection, could result in extensive antigen-antibody immune complexes that cannot be quickly cleared in a subset of patients and thus create a type III hypersensitivity immune reaction and cause Kawasaki disease or Kawasaki disease symptoms (also known as multisystem inflammatory syndrome) in a subset of patients. Extensive binding of antibodies to viral antigens can create antigen-antibody immune complexes, which, if not eliminated in certain individuals having dysfunctional complement systems, can start inflammatory type III hypersensitivity symptoms, including protease releases that can disrupt epithelium, mesothelium, and endothelium basement membranes, and induce pervasive inflammation throughout the body. This could continue after SARS-CoV-2 infections end if the first wave of protease attacks on basement membranes created new secondary autoantibodies and new uncleared antigen-antibody immune complexes.

[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.

Reactivation of human herpesviruses 6 and 7 in Kawasaki disease.

Objectives: Kawasaki disease (KD) is one of the most common childhood vasculitides. Some serological studies have suggested an etiological relationship between KD and human herpesvirus (HHV)-6 or HHV-7. However, primary or reactivated HHV-6 and -7 has not been fully investigated in patients with KD. Methods: Twenty-three patients with KD were prospectively enrolled in this study. Peripheral blood was collected in the acute and convalescence phases, and HHV-6 and -7 viral loads were measured by real-time PCR. Results: In the acute phase, HHV-6 and -7 DNA was detected in 7 (30%) patients each, compared to 13 (57%) and 9 (39%) patients in the convalescence phase, respectively. HHV-6 and -7 DNA loads were significantly higher in the convalescence phase than in the acute phase. Significant increases in HHV-6 and -7 DNA loads were not observed in disease control patients. Taking into account HHV-6 and -7 serostatus, reactivation of HHV-6 and -7 was observed in 7 and 9 patients, respectively. KD patients with HHV-6 reactivation showed higher C-reactive protein levels and more frequently required steroid therapies than patients without reactivation. Conclusion: HHV-6 and -7 reactivation is frequent in KD patients. HHV-6 reactivation might exacerbate the severity of KD.

Soluble CD163, a unique biomarker to evaluate the disease activity, exhibits macrophage activation in systemic juvenile idiopathic arthritis.

This study aims to investigate the clinical significance of serum soluble CD163 (sCD163) levels as a predictor of the disease activity of systemic juvenile idiopathic arthritis (s-JIA). In this study, we examined 63 patients with s-JIA, four with Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis (EBV-HLH), and seven with Kawasaki disease (KD), along with 14 healthy controls. We quantified serum cytokine levels (sCD163, neopterin, IL-18, IL-6) by enzyme-linked immunosorbent assay and compared the results with the clinical features of s-JIA. Serum sCD163 levels were significantly elevated in patients with s-JIA associated macrophage activation syndrome (MAS) and EBV-HLH compared to those in patients with acute-phase s-JIA and KD. In addition, serum sCD163 levels profoundly increased with the progress of MAS and correlated positively with the disease activity of s-JIA, even in patients receiving tocilizumab. Furthermore, serum sCD163 levels significantly decreased in the inactive phase compared to those in the active phase and normalized in remission. The correlation between macrophage activation and serum sCD163 levels might be a unique indicator of the disease activity and a potential diagnostic laboratory criterion for clinical remission in patients with s-JIA, including those receiving tocilizumab.

Clinical and Virologic Characteristics May Aid Distinction of Acute Adenovirus Disease from Kawasaki Disease with Incidental Adenovirus Detection.

Incidental adenovirus detection in Kawasaki disease (KD) is important to differentiate from acute adenovirus disease. Twenty-four of 25 children with adenovirus disease and mimicking features of KD had <4 KD-like features, predominance of species B or E, and higher viral burden compared with those with KD and incidental adenovirus detection.