Biologically informed machine learning modeling of immune cells to reveal physiological and pathological aging process (preprint)

The immune system undergoes progressive functional remodeling from neonatal stages to old age. Therefore, understanding how aging shapes immune cell function is vital for precise treatment of patients at different life stages. Here, we constructed the first transcriptomic atlas of immune cells encompassing human lifespan, ranging from newborns to supercentenarians, and comprehensively examined gene expression signatures involving cell signaling, metabolism, differentiation, and functions in all cell types to investigate immune aging changes. By comparing immune cell composition among different age groups, HLA highly expressing NK cells and CD83 positive B cells were identified with high percentages exclusively in the teenager (Tg) group, whereas CD4_CTL precursors were exclusively enriched in the supercentenarian (Sc) group. Notably, we found that the biological age (BA) of pediatric COVID-19 patients with multisystem inflammatory syndrome accelerated aging according to their chronological age (CA). Besides, we proved that inflammatory shift- myeloid abundance and signature correlate with the progression of complications in Kawasaki disease (KD). Finally, based on those age-related immune cell compositions, we developed a novel BA prediction model, PHARE (https://xiazlab.org/phare/), which applies to both scRNA-seq and bulk RNA-seq data. Overall, our study revealed changes in immune cell proportions and function associated with aging, both in health and disease, and provided a novel tool for successfully capturing features that accelerate or delay aging.

Comparison of the type and prevalence of cardiac involvement among children hospitalized with COVID-19 and Multisystem Inflammatory Syndrome in Children: A cross-sectional study (preprint)

Background: Since the outbreak of COVID-19 in late 2019, more than 772 million individuals have been infected. There are numerous reports and studies about the complications and effects of this viral disease on different systems of the body. One of the important complications of COVID-19 in children is a condition named “Multisystem Inflammatory syndrome in Children (MIS-C)” which has some manifestations similar to Kawasaki disease or sepsis. Methods: In this study, we retrospectively compared the cardiac complications of COVID-19 and MIS-C in individuals under 18 years old of age, admitted to the Children’s Hospital of Bandar-Abbas, Iran, in an 18-months period of time. Results: The prevalence of mitral regurgitation in MIS-C and COVID-19 groups was 36.4% and 15.6%, respectively. The prevalence of tricuspid regurgitation in MIS-C and COVID-19 groups was 62.8% and 34.6%, respectively. The prevalence of positive result for troponin enzyme level in MIS-C and COVID-19 groups was 24.2% and 7.4%, respectively. Conclusion: This study showed that the prevalence of cardiac involvement in MIS-C patients was greater than COVID-19 patients. Additionally, the most cardiac complications among these groups of patients were tricuspid regurgitation and mitral regurgitation.

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.

Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature.

BACKGROUND: To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections. METHODS: Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39). RESULTS: In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV. CONCLUSIONS: MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.

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.

Is Kawasaki Disease Caused by a Respiratory Virus?

BACKGROUND: Kawasaki disease is characterized by high fever, rash, cervical lymphadenopathy, conjunctival injection, oral mucous membrane changes and swelling of the extremities followed by skin sloughing. Despite >50 years of study, no bacterial, viral or other infectious agent has been consistently associated with the illness. The lockdown and social distancing for COVID-19 in March 2020 led to a marked decrease in respiratory virus circulation. This provided an "experiment of nature" to determine whether Kawasaki disease would decline in parallel. METHODS: Discharge ICD-10 diagnosis codes were obtained from the Vizient Clinical Data Base for Kawasaki disease and respiratory viruses, and analyzed for the age group < 5 years. Weekly respiratory virus positivity data were also obtained from BioFire Diagnostics. RESULTS: Common enveloped respiratory viruses declined precipitously from April 2020 through March 2021 to levels at or below historical seasonal minimum levels. Kawasaki Disease declined about 40% compared with 2018-2019, which is distinctly different from the pattern seen for the enveloped respiratory viruses. Strong seasonality was seen for Kawasaki disease as far back as 2010, and correlated most closely with respiratory syncytial virus, human metapneumovirus and less so with influenza virus suggesting there is a baseline level of Kawasaki disease activity that is heightened during yearly respiratory virus activity but that remains at a certain level even in the near total absence of respiratory viruses. CONCLUSIONS: The striking decrease in enveloped respiratory viruses after lockdown and social distancing was not paralleled by a comparable decrease in Kawasaki disease incidence, suggesting a different epidemiology.

Multisystem inflammatory syndrome in children: A dysregulated autoimmune disorder following COVID-19.

Multisystem inflammatory syndrome in children (MIS-C) is a dysregulated autoimmune-mediated illness in genetically susceptible patients following COVID-19 with an interval of 2-6 weeks. The median age of patients with MIS-C is 6-11 years. Most common manifestations are involvement of gastrointestinal tract, cardiovascular system, hematological system, and mucocutaneous system. Respiratory tract, neurological system, musculoskeletal system, and kidney are less frequently affected. Mucocutaneous manifestations and coronary artery abnormalities characteristic for Kawasaki disease (KD) may be observed in a significant proportion of MIS-C patients that may make the differential diagnosis be difficult for some patients, especially in the post-pandemic era. The mortality rate is 1-3%. Management and prognosis of MIS-C are similar to that of KD. MIS-C and KD may share a common pathogenic process. Based on the observation of MIS-C-like illness in uninfected neonates, i.e. multisystem inflammatory syndrome in neonates, both MIS-C and KD may be a consequence of dysregulated, over-exaggerated humoral immune responses triggered by a specific infectious agent.

Multisystem Inflammatory Syndrome in Children and Kawasaki Disease: A Spectrum of Postinfectious Hyperinflammatory Disease.

Kawasaki disease and multisystem inflammatory syndrome in children are hyperinflammatory conditions that share similar emerging pathophysiology hypotheses, clinical features, treatment strategies, and outcomes. Although both conditions have key differences, growing evidence suggests that both conditions might be closely related on a larger spectrum of postinfectious autoimmune responses.

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

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

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.

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

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

Comparison of Characteristics and Outcomes of Multisystem Inflammatory Syndrome, Kawasaki Disease and Toxic Shock Syndrome in Children.

Background and Objectives: Since the first cases of multisystem inflammatory syndrome in children (MIS-C) in April 2020, the diagnostic challenge has been to recognize this syndrome and to differentiate it from other clinically similar pathologies such as Kawasaki disease (KD) and toxic shock syndrome (TSS). Our objective is to compare clinical signs, laboratory data and instrumental investigations between patients with MIS-C, KD and TSS. Materials and Methods: This retrospective observational study was conducted at the Children's Clinical University Hospital, Latvia (CCUH). We collected data from all pediatric patients <18 years of age, who met the Centers for Disease Control and Prevention case definition for MIS-C, and who presented to CCUH between December 2020 and December 2021. We also retrospectively reviewed data from inpatient medical records of patients <18 years of age diagnosed as having KD and TSS at CCUH between December 2015 and December 2021. Results: In total, 81 patients were included in this study: 39 (48.1%) with KD, 29 (35.8%) with MIS-C and 13 (16.1%) with TSS. In comparison with TSS and KD, patients with MIS-C more often presented with gastrointestinal symptoms (abdominal pain (p < 0.001), diarrhea (p = 0.003)), shortness of breath (p < 0.02) and headache (p < 0.003). All MIS-C patients had cardiovascular involvement and 93.1% of MIS-C patients fulfilled KD criteria, showing higher prevalence than in other research. Patients with KD had higher prevalence of cervical lymphadenopathy (p < 0.006) and arthralgias (p < 0.001). In comparison with KD and TSS, MIS-C patients had higher levels of ferritin (p < 0.001), fibrinogen (p = 0.04) and cardiac biomarkers, but lower levels of platelets and lymphocytes (p < 0.001). KD patients tended to have lower peak C-reactive protein (CRP) (p < 0.001), but higher levels of platelets. Acute kidney injury was more often observed in TSS patients (p = 0.01). Pathological changes in electrocardiography (ECG) and echocardiography were significantly more often observed in MIS-C patients (p < 0.001). Conclusions: This research shows that MIS-C, KD and TSS have several clinical similarities and additional investigations are required for reaching final diagnosis. All the patients with suspected MIS-C diagnosis should be examined for possible cardiovascular involvement including cardiac biomarkers, ECG and echocardiography.

Multisystem inflammatory syndrome in children associated with Bacille Calmette-Guérin scar: a case presentation.

BACKGROUND: During Coronavirus disease of 2019 (COVID-19) pandemic, the WHO reported a noticeable increase in Kawasaki disease prevalence in countries where Kawasaki disease is rare. This newly seen disease, unlike typical Kawasaki disease, tends to appear at a later age, has prominent gastrointestinal findings, higher rates of myocarditis and coronary artery involvement and a greater need for admission to the intensive care unit (ICU). Induration of the Bacillus Calmette-Guerin (BCG) scar is a rare finding seen in multisystem inflammatory syndrome (MIS-C). This is the second reported case of erythema and induration of the BCG scar in a 1-year-old boy with MIS-C. CASE PRESENTATION: The Arabic boy presented with high resistant fever, nausea/vomiting, diarrhea, erythematous lips, and conjunctivitis. He later developed induration of his BCG scar, diffuse rash and desquamation on fingers and toes. He had a history of COVID-19 exposure as his IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were positive. Based on his clinical findings and repeated lab results, he was diagnosed with MIS-C with Kawasaki features and treated with intravenous immune globulin (IVIG) followed by methylprenisolone and aspirin. CONCLUSIONS: Reaction at the BCG inoculation site is not a diagnostic criteria for Kawasaki, but it is seen clinically in 30-50% of the patients. We report the case of a 1-year-old boy diagnosed with MIS-C presenting with erythema and induration of BCG scar. Further studies are needed to explore this clinical presentation, especially in the countries that have BCG vaccination programs, and to determine the mechanisms of MIS-C.

Expanding the Differential for Alternative Diagnoses in the Workup of Multisystem Inflammatory Syndrome in Children.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare inflammatory syndrome associated with SARS-CoV-2 infection. Children are increasingly admitted for MIS-C evaluation, but instead found to have alternative diagnoses. METHODS: Retrospective study of all pediatric patients <21 years of age hospitalized between August 1, 2020, and July 31, 2021, with clinical concern for MIS-C at the time of presentation were identified through use of an institutional computerized MIS-C order entry set. Final diagnoses were then collected through primary review of the medical record from the time of initial presentation through 1-month postdischarge. RESULTS: Of 359 cases identified through the MIS-C order entry set, 126 (35.1%) met criteria for MIS-C, 28 had Kawasaki Disease (KD) (7.8%), and 11 cases met criteria for both MIS-C and KD (3.1%), leaving 194 (54.0%) patients ruled out and categorized as "MIS-C mimickers." Infectious diagnoses were the most common MIS-C mimickers (78.9%). Of the infectious etiologies, bacterial (51.0%) and viral (52.3%) etiologies were seen with similar frequency. CONCLUSIONS: We describe MIS-C mimickers spanning multiple subspecialties, with infectious etiologies predominating, which can aid clinicians in the consideration of diagnostic testing, with the goal of achieving timely and accurate diagnoses.

[Kawasaki disease cytokine release syndrome and Kawasaki disease shock syndrome: A case report]. / Síndrome de tormenta de citocinas y síndrome de choque por enfermedad de Kawasaki: reporte de un caso.

BACKGROUND: Kawasaki disease is a vasculitis of small and medium vessels, with a high prevalence throughout the world. In addition to coronary aneurysms, this vasculitis can lead to a number of systemic complications, including Kawasaki disease shock syndrome and Kawasaki disease cytokine storm syndrome. CASE REPORT: : Case report: A 12-year-old male patient, who began his condition with heartburn, sudden fever of 40 ºC and jaundice, for which he was prescribed treatment with antipyretics and bismuth subsalicylate, without satisfactory reaction. Gastroalimentary content was added three times, and centripetal maculopapular dermatosis. After 12 hospital stays, he was evaluated by personnel from the Pediatric Immunology service, who reported data on hemodynamic instability due to persistent tachycardia for hours, immediate capillary refill, intense pulse, oliguria of 0.3 mL/kg/h of partial urinary output with condensed urine; the systolic blood pressure figures were below the 50% percentile, and there was polypnea and limit saturation in 93%. In the paraclinical studies, the rapid decrease in platelet count (from 297,000 to 59,000 in 24 hours), as well as a neutrophil-lymphocyte index of 12, drew attention. The concentrations of NS1 size, IgM and IgG for dengue and PCR for SARS virus were determined. -CoV-2, which were negative. The definitive diagnosis of Kawasaki disease was established with Kawasaki disease shock syndrome. The evolution of the patient was satisfactory, with a decrease in fever after the administration of gamma globulin on the tenth day of hospitalization, and a new protocol with prednisone (50 mg/day) was started, when the cytokine storm syndrome due to illness was integrated. Kawasaki syndrome simultaneous with pre-existing disorders, that is, Kawasaki disease and Kawasaki disease shock syndrome due to thrombocytopenia, hepatosplenomegaly, fever, lymphadenopathy; in addition, ferritin of 605 mg/dL and transaminasemia. The control echocardiogram did not show coronary abnormalities and hospital discharge was granted 48 hours after starting treatment with the corticosteroid, with a 14-day follow-up plan. CONCLUSIONS: Kawasaki disease is an autoimmune vasculitis that can worsen with simultaneous syndromes associated with high mortality. It is important to know this type of alterations and their differences to properly discern and implement effective and timely treatment.

INTRODUCCIÓN: La enfermedad de Kawasaki es una vasculitis de pequeños y medianos vasos, con elevada prevalencia en todo el mundo. Además de los aneurismas coronarios, esta vasculitis puede generar diversas complicaciones sistémicas, como el síndrome de choque por enfermedad de Kawasaki y el síndrome de tormenta de citocinas por enfermedad de Kawasaki. REPORTE DE CASO: Paciente masculino de 12 años de edad, que inició su padecimiento con pirosis, fiebre súbita de 40 ºC e ictericia, por lo que se le prescribió tratamiento con antipiréticos y subsalicilato de bismuto, sin reacción satisfactoria. Se agregó vómito de contenido gastroalimentario en tres ocasiones y dermatosis maculopapular centrípeta. Después de 12 horas de estancia intrahospitalaria fue valorado por personal del servicio de Inmunología Pediátrica, quienes informaron datos de inestabilidad hemodinámica por taquicardia persistente, llenado capilar inmediato, pulso intenso, oliguria de 0.3 mL/kg/h de gasto urinario parcial con orina condensada; las cifras de tensión arterial sistólica se encontraban debajo del percentil 50%, y había polipnea y saturación limítrofe en 93%. En los estudios paraclínicos llamó la atención el rápido descenso del conteo plaquetario (de 297,000 a 59,000 en 24 horas), así como el índice neutrófilo-linfocito de 12. Se determinaron las concentraciones de antígeno NS1, IgM e IgG para dengue y PCR para virus SARS-CoV-2, que resultaron negativas. Se estableció el diagnóstico definitivo de enfermedad de Kawasaki con síndrome de choque por enfermedad de Kawasaki. La evolución del paciente fue satisfactoria, con disminución de la fiebre luego de la administración de gammaglobulina en el décimo día de hospitalización, y se inició un nuevo protocolo con prednisona (50 mg/día), al integrarse el síndrome de tormenta de citocinas por enfermedad de Kawasaki simultáneo con las alteraciones preexistentes, es decir: enfermedad de Kawasaki y síndrome de choque por enfermedad de Kawasaki por trombocitopenia, hepatoesplenomegalia, fiebre, adenopatías; además, ferritina de 605 mg/dL y transaminasemia. El ecocardiograma de control no mostró modificaciones coronarias y se otorgó el alta hospitalaria después de 48 horas de iniciar el tratamiento con el corticosteroide, con plan de seguimiento en 14 días. CONCLUSIONES: La enfermedad de Kawasaki es una vasculitis autoinmunitaria que puede agravarse con síndromes simultáneos asociados y generar elevada mortalidad. Es importante conocer este tipo de alteraciones y sus diferencias para discernir de forma adecuada e implementar el tratamiento eficaz y oportuno.

Prolonged Fever: Kawasaki Disease in a Pediatric Patient With COVID-19.

Kawasaki disease (KD) is the leading cause of acquired heart disease. The cardiac clinical features seen with KD require diagnosis and treatment within 10 days of symptoms to decrease the risk of complications. This case report examines the complexity of prolonged fever in a pediatric patient with a positive test for severe acute respiratory coronavirus 2 and meets the KD criteria.

Pathogenic and therapeutic roles of cytokines in Kawasaki diseases.

Infancy and early childhood are the most common ages for acute pyretic Kawasaki disease (KD). Although the etiology remains a mystery, the current concept is that KD is caused by a contagious pathogen that infects the genetically vulnerable and induces an inflammatory mechanism aimed at cardiovascular organs. Resolving the inflammatory process and decreasing the incidence of coronary anomalies, namely coronary aneurysms, are two benefits of high-dose intravenous immunoglobulin (IVIG) administration. The etiology of KD has been linked to a large number of cytokines and treatment strategies to regulate these cytokines have been suggested. This review will focus on the critical role of cytokines in disease development and possible treatment approaches and potential clinical applications.