Search Results (184)

Background: Acute kidney injury (AKI) is increasingly recognised in children with acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C), yet the long-term renal consequences in younger paediatric populations remain unclear. Most studies focus on acute illness or mixed-age cohorts, with limited data specific to children aged 0–12 years. Objectives: This study aimed to systematically identify, evaluate, and synthesise evidence on post-acute (≥30 days) and long-term (≥90 days) kidney outcomes following SARS-CoV-2 infection or MIS-C in children aged 0–12 years, including chronic kidney disease (CKD), eGFR decline, proteinuria, haematuria, hypertension, and need for kidney replacement therapy. Methods: We searched MEDLINE, Embase, CINAHL, and PubMed (December 2019–30 November 2025), following PRISMA 2020 guidelines and a registered PROSPERO protocol (CRD420251241949). Observational studies reporting kidney outcomes ≥30 days post-infection in children aged 0–12 years were included. Risk of bias was assessed using the Newcastle–Ottawa Scale or ROBINS-I. Owing to heterogeneity and absence of ≥3 comparable datasets, a narrative synthesis was performed. Results: Seven studies met inclusion criteria (five MIS-C cohorts, two acute COVID-19 cohorts). Only a subset provided extractable data specific to children aged 0–12 years. Follow-up ranged from 30 days to 12 months; four studies reported outcomes ≥ 180 days. Across all studies, no incident CKD, sustained eGFR decline, or kidney replacement therapy were reported among children completing long-term follow-up; however, most long-term outcome data were derived from MIS-C cohorts with median ages around 8–11 years that included some adolescents, rather than exclusively children aged 0–12 years. One MIS-C study reported long-term hypertension in 14% of children. A cross-sectional Italian cohort of mild COVID-19 demonstrated hyperfiltration, proteinuria, and microhaematuria at ~3 months, though chronicity could not be assessed due to absence of baseline values. A large US EHR-based cohort identified increased CKD risk after COVID-19 in the broader < 21-year population; however, 0–12-year-specific event counts were not reported, preventing quantitative synthesis for young children. Conclusions: Evidence on long-term kidney outcomes after SARS-CoV-2 infection in children aged 0–12 years remains limited, and only a small subset of studies provided extractable, age-specific data. On the other hand, MIS-C cohorts generally show favourable renal recovery, small sample sizes, lack of control groups, and short follow-up restrict confidence in these findings. Large paediatric EHR studies suggest potential long-term renal risk in broader paediatric populations, highlighting the need for age-stratified, prospective cohorts with serial eGFR, urine studies, and blood pressure assessments. Until definitive evidence emerges, structured renal follow-up may be warranted for children with AKI or MIS-C during COVID-19. Full article

Posterior Reversible Encephalopathy Syndrome (PRES) is a rare but potentially reversible neurological manifestation associated with Multisystem Inflammatory Syndrome in Children (MIS-C). We report an eight-year-old boy who developed PRES secondary to MIS-C following asymptomatic SARS-CoV-2 exposure. The patient presented with fever, seizures, decreased consciousness, and visual disturbances. MRI revealed characteristic bilateral parieto-occipital and posterior temporal cortical–subcortical hyperintensities, while CT scans were normal. The patient achieved full neurological recovery with corticosteroid therapy, blood pressure control, and supportive management. This case underscores the importance of early MRI in detecting PRES when clinical or CT findings are inconclusive, emphasizing the need for heightened awareness among pediatric clinicians to prevent irreversible neurological sequelae. Full article

Background and Objectives: The aim of this study was to identify clinical features and laboratory findings that correlate with and predict pathological echocardiographic findings in children diagnosed with Multisystem Inflammatory Syndrome. Materials and Methods: Retrospective study included all patients aged 0–18 diagnosed with Multisystem Inflammatory Syndrome and hospitalized at our clinic from July 2020 to December 2022. The clinical and laboratory data of 61 patients were studied and compared between two subgroups (normal/abnormal echocardiography). Results: Elevated values of high-sensitivity troponin I were observed in 65.57% patients with MIS-C. The mean high-sensitivity troponin I value in the whole sample was 400.89 ± 1989.31 pg/mL. In patients with pathological echocardiographic findings, the mean value was 1240.24 ± 3609 pg/mL, while in patients with normal echocardiographic findings, it was 52.87 ± 71.86 pg/mL. Even though mean value was higher in the group of patients with abnormal echocardiography, no statistically significant difference was observed between high-sensitivity troponin I values in patients with and without pathological echocardiographic findings. Troponin levels were not in good correlation with pathological echocardiographic findings (point-biserial correlation; rpb = 0.25, p = 0.054) and were not good predictors of pathological echocardiographic findings (logistic regression; Chi² = 3.77, p = 0.052). Logistic regression showed significant positive correlation of blood urea nitrogen levels and the degree of fever with abnormal echocardiographic findings (Chi² = 10.04, p 0.002/Chi² = 6.10, p = 0.013, respectively). Conclusions: Only blood urea nitrogen levels and high fever showed statistically significant correlation and predictive value for abnormal echocardiographic findings in children with Multisystem Inflammatory Syndrome. High sensitive troponin I had no significant power to discriminate between normal and abnormal echocardiographic findings. Full article

The SARS-CoV-2 pandemic has posed global medical challenges due to its ability to affect multiple organ systems. Among the post-COVID-19 complications, multisystem inflammatory syndrome has emerged as a severe condition affecting both children (MIS-C) and adults (MIS-A). This review aims to compile and analyze published data to investigate clinical characteristics, laboratory findings, and outcomes of MIS post-COVID-19. A comprehensive search of various databases was conducted to identify studies reporting MIS-related complications in pediatric and adult populations post-COVID-19 infection. Screening, data extraction, and cross-checking were performed by two independent reviewers. Only 64 studies met our inclusion criteria, and compiled results revealed that cardiac complications were the predominant manifestation followed by gastrointestinal, hematologic, neurological, and mucocutaneous involvement. Laboratory findings consistently demonstrated elevated inflammatory markers including CRP, ferritin, D-dimer, and IL-6. Most patients required hospitalization, and many needed intensive care; treatment typically involved IVIG, corticosteroids, and biologic therapies. While most patients recovered, a subset experienced persistent complications. These findings highlight the importance of early recognition, multidisciplinary management, and structured follow-up for MIS. Future research is warranted to clarify the underlying mechanisms, risk factors, and long-term outcomes associated with MIS in post-COVID-19 patients. Full article

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-infectious complication of SARS-CoV-2, often with cardiac involvement. Myocardial strain imaging may detect dysfunction missed by conventional echocardiography. The objectives of this study are to characterize cardiac manifestations of MIS-C and assess the value of strain imaging in children with preserved and reduced left ventricular ejection fraction (LV-EF). Methods: We retrospectively analyzed 22 MIS-C patients admitted between September 2020 and January 2024, all with cardiac involvement. Clinical, laboratory, and echocardiographic data—including 2D and speckle-tracking strain—were collected at the day of worst dysfunction (DWD) and discharge (DD) and compared with 22 matched controls. Results: Median age was 4.65 years; 59% male; 45% overweight/obese. LV systolic dysfunction (LV-EF < 50%) occurred in 54.5%, coronary abnormalities in 36.4%, and pericardial effusion in 95.5%. LV global longitudinal strain (LVGLS) was significantly lower than controls at the DWD (−15.45 ± 4.76%, p < 0.0001) and DD (−20.63 ± 4.66%, p = 0.014). Strain abnormalities persisted despite LV-EF recovery, and even patients with preserved LV-EF showed significant segmental strain reduction. LVGLS and apical infero-septal strain were strongest predictors of reduced LV-EF. Conclusions: MIS-C often causes systolic dysfunction and coronary changes, but strain imaging reveals persistent subclinical myocardial injury. Long-term cardiac monitoring is warranted. Full article

Background/Objectives: Multisystem inflammatory syndrome in children (MIS-C), a rare but serious post-acute hyperinflammatory condition that occurs in children 2–6 weeks after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection or exposure, varies between countries. Despite its serious nature, most children recover without any sequelae. The most frequently reported long-term sequelae are coronary artery aneurysms. This study aimed to describe the epidemiological profile, clinical characteristics (including cardiac manifestations), treatment, and outcomes of multisystem inflammatory syndrome in children (MIS-C) under 14 years of age with SARS-CoV-2 between February 2020 and November 2021 in Kuwait. Methods: Data on sociodemographic factors, co-morbidities, presenting signs and symptoms, as well as laboratory and echocardiography findings were retrieved from the Pediatric COVID registry (PCR-Q8 registry). Results: Of the one hundred and two patients with a provisional diagnosis of MIS-C, eighty-three patients fulfilled the WHO criteria of MIS-C. Thirty-nine of the MIS-C patients were admitted to the intensive care unit, and only one child died due to cardiogenic shock. Sixteen patients from the pediatric MIS-C cohort were diagnosed with cardiac abnormalities. Sixteen patients from the pediatric MIS-C cohort were diagnosed with cardiac abnormalities. Most (63% (10/16)) of the patients had coronary abnormalities, nine patients (56%) had myocardial dysfunction, and six patients (38%) had dual pathologies. Pericarditis occurred in three patients only, whilst six patients (38%) had dual pathologies. Pericarditis occurred in three patients only. Conclusions: MIS-C appears to affect younger children in Kuwait than in other countries; however, the clinical pattern is consistent with other countries. Further studies of an analytical nature are recommended to identify the risk factors associated with MIS-C and its cardiac sequalae to allow for proactive risk reduction. Full article

The Coronavirus disease 2019 (COVID-19) pandemic had a profound global impact, yet children exhibited distinct clinical and epidemiological patterns compared to adults. Pediatric cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were generally characterized by milder disease, lower hospitalization rates, and few long-term sequelae. However, a subset of children developed severe complications such as multisystem inflammatory syndrome in children (MIS-C), highlighting the heterogeneity in disease presentation. Differences in immune system maturity and comorbidities likely contribute to the age-dependent manifestation of SARS-CoV-2 and other respiratory viruses. Persistent SARS-CoV-2 infection, particularly in immunocompromised individuals, has been implicated in the emergence of new viral variants with immune escape characteristics due to ongoing viral replication in the presence of selective pressure. While SARS-CoV-2 evolution in persistently infected adults has been well-documented, it is less clear how the virus evolves during persistent infection in the pediatric population. To address this question, we performed viral whole genome sequencing of longitudinal specimens collected from immunocompetent and immunocompromised pediatric COVID-19 patients. Similarly to what has been observed in adult cohorts, mutations associated with enhanced viral fitness and immune escape arose intra-host over time. Intra-host diversity accumulated at similar rates in immunocompetent and immunocompromised children, though more mutations overall were observed in the immunocompromised cohort due to the longer infection time courses. Overall, we identified similar viral evolutionary trends over the course of infection despite clinical differences in pediatric COVID-19 manifestation and severity. This similarity suggests that persistent infection in children may be an additional, but not unique, source of ongoing viral diversification. Full article

Macrophage activation syndrome (MAS), a hyperinflammatory condition driven by uncontrolled immune activation, is widely recognized as a critical complication in pediatric septic shock. This syndrome shares pathophysiological features with hemophagocytic lymphohistiocytosis (HLH) and other cytokine storm syndromes, and it contributes to significant morbidity and mortality in pediatric and adult patients. Hyperferritinemia—a hallmark of MAS—is not only a diagnostic clue but also a prognostic marker for poor outcomes in sepsis. High ferritin levels are strongly suggestive of MAS, yet even moderate elevations in combination with the trend of ferritin levels can be indicative of heightened mortality risk. Distinguishing MAS from severe sepsis or other hyperinflammatory syndromes in children (such as multisystem inflammatory syndrome in children (MIS-C)) can be challenging, as clinical features often overlap. However, early recognition and timely immunomodulatory therapy, particularly corticosteroids and targeted biologic agents, can be life-saving. Recent advances emphasize a syndromic approach to diagnosing MAS within the spectrum of hyperferritinemic sepsis, using scoring tools or MAS-specific criteria adapted to sepsis or MIS-C contexts. Ongoing studies aim to refine biomarker-based stratification and therapeutic algorithms. This review synthesizes current knowledge on MAS as a complication of sepsis, including the diagnostic importance of ferritin levels, differential diagnosis with other cytokine storm syndromes, and the latest therapeutic approaches. It underscores the importance of early suspicion and intervention to reverse immune dysregulation and improve outcomes in critically ill pediatric patients. Full article

The X-linked TLR7 rs179008 T allele has been associated with altered antiviral immunity. Given their shared inflammatory pathways and higher pediatric mortality rates in Brazil during the pandemic, we investigated their association with multisystem inflammatory syndrome in children (MIS-C) together with Kawasaki disease (KS) following SARS-CoV-2 infection. A cross-sectional study (2021–2022) analyzed 73 hospitalized children (<13 years) with confirmed COVID-19. Genotyping for TLR7 rs179008, TLR8 (rs3764879, rs2407992), and TLR3 rs3775291 was performed via PCR and Sanger sequencing. MIS-C/KS cases were identified using CDC criteria, with severity classified by the need for ICU care. Statistical analysis included Fisher’s exact test and relative risk (RR) calculations. Hemizygous boys carrying the TLR7 T allele had a 1.87-fold higher risk of MIS-C/KS (p = 0.007) and a 1.75-fold increased risk of severe or critical outcomes. The T allele frequency was 2.6× higher in MIS-C/KS cases versus other COVID-19 presentations. All fatalities occurred in boys (3/8 MIS-C cases) with one T-allele carrier. No associations were found for TLR8 or TLR3 variants. The TLR7 rs179008 T allele is a potential genetic risk factor for severe post-COVID-19 inflammatory syndromes in boys, likely due to impaired immune signaling. These findings highlight its utility as a biomarker for risk stratification in pediatric populations. Full article

Optimal treatment for non-critically ill multisystem inflammatory syndrome in children (MIS-C) remains unclear. We evaluated short-term outcomes in mild to moderately ill hospitalized MIS-C patients fulfilling CDC 2020 and CDC/CTSE 2023 criteria and treated between April 2020 and March 2022 with either intravenous immunoglobulin (IVIG) monotherapy (Group A, n = 17) or IVIG plus corticosteroids (GC) (Group B, n = 22). Cardiovascular clinical parameters, inflammatory markers, and cardiac imaging were compared on days 1, 3, and 5 relative to day 0. The two groups had no significant differences in demographics or illness severity. Group B showed improvement in heart rate (17.8; 95% CI [9.74, 25.8]), mean blood pressure (5.63 [1.61, 9.64]), and body temperature (1.45 [0.94, 1.95]) by day 1, followed by improvement in albumin (0.43 [0.2, 0.84]), CRP (7.56 [3.0, 12.11]), D-dimer (2344 [488.7, 4200.2]), ferritin (1448 [−609.4, 3505.5]), fibrinogen (110 [44.4, 176]), lymphocyte count (1006 [63.5, 1948]), and NT-proBNP (2901 [−349.3, 6153]) by day 3 and left ventricular ejection fraction by day 4–5 (3.84 [0.55, 8.23]). All results were statistically significant (p < 0.05). Group A required more additional therapies, with no difference in hospital stay. Our study concludes that combined IVIG and GC therapy yielded better short-term outcomes than IVIG monotherapy in this patient population, with improvement in cardiovascular clinical parameters preceding changes in inflammatory markers and cardiac imaging. Full article

Although Kawasaki disease (KD) has been known since 1967, when it was first described by Dr. Tomisaku Kawasaki, the literature indicates that its etiology—similarly to Multisystem Inflammatory Syndrome in Children (MIS-C)—remains largely unclear and is the subject of intensive research. The former disease, which typically occurs shortly after infection, is the most common cause of primary vasculitis in children worldwide. The latter—MIS-C, associated with SARS-CoV-2 infection—is characterized by involvement of at least two organ systems. Undoubtedly, both diseases exhibit heightened immune system activity and significant inflammation. In recent years, increasing attention has been directed towards alterations in the microbiota observed in affected patients. We undertake an analysis and systematic review of the current scientific findings in this field. We emphasize the role of the microbiome—which encompasses not only bacteria but also viruses, fungi, parasites, and archaea—in health and disease. We track its composition from birth and highlight factors influencing its diversity, such as the mode of delivery. We recognize the microbiome’s role in reducing the likelihood of allergic diseases in children and its interactions with the immune system. In addition to comparing the pathomechanisms and clinical manifestations of KD and MIS-C, also known as Pediatric Inflammatory Multisystem Syndrome (PIMS), we investigate microbiota alterations in these conditions and analyze potential applications of microbiome knowledge, for example, in identifying diagnostic markers. We also point out potential directions for future research, such as the use of short-chain fatty acids (SCFAs) in MIS-C and the long-term changes in the gut microbiota associated with these diseases, which remain poorly documented and currently represent significant gaps in knowledge. Full article

Backgrounds and Objectives: Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but potentially severe complication of SARS-CoV-2 infection, with increasingly reported renal manifestations. Materials and Methods: The aim of this retrospective study was to compare clinical and laboratory characteristics across age categories, with special emphasis on renal function. We analysed data from 64 patients with MIS-C treated between July 2020 and December 2023. Results: In children under 3 years of age, there was a higher prevalence of leucocytosis, elevated platelet counts, and anaemia, along with a lower frequency of complications. The 3–6-year age group was characterized by the presence of rash, hypoalbuminemia, and elevated transaminases. The 7–12-year age group showed the highest rate of organ dysfunction. In adolescents (13–18 years), neurological symptoms, the highest BMI values, the greatest prevalence of comorbidities, leukopenia, lymphopenia, and elevated GGT levels were observed. The incidence of acute kidney injury (AKI) was 6.3% (n = 4/64). Following treatment, the majority of patients achieved full recovery (n = 61/64; 95.2%). Conclusions: There are pronounced age-related differences in the clinical presentation of MIS-C, with distinct immune and clinical patterns suggesting developmental influences on disease expression and outcomes. Older children showed a higher prevalence of comorbidities and organ dysfunction compared to younger patients. Notably, this study found a markedly lower incidence of acute kidney injury (6.3%) compared to previously reported rates (20–30%), indicating potential regional or age-related protective factors. These findings highlight the importance of age-specific evaluation in MIS-C and underscore the need for further multicentre research to refine therapeutic protocols. Full article

Multisystemic inflammatory syndrome in children (MIS-C) is a rare but potentially severe condition that affects multiple organ systems. This study aimed to assess the clinical characteristics and outcomes of patients diagnosed with multisystemic inflammatory syndrome in children (MIS-C) associated with COVID-19. A 12-month prospective study was conducted at the “Grigore Alexandrescu” Clinical Emergency Hospital for Children, Bucharest. This study included children aged 0–18 years who were diagnosed with MIS-C, as defined by the World Health Organization (WHO), the Royal College of Paediatrics and Child Health (RCPCH), and the Centers for Disease Control and Prevention (CDC) criteria. Data on age, gender, clinical and laboratory findings, treatment, and outcomes were analyzed. Follow-up evaluations occurred at one, three, six, nine, and twelve months post-discharge. Among 36 patients (47.3% female, 52.7% male; mean age, 9.9 years), fever and inflammatory syndrome were present in all patients. Other common symptoms included mucocutaneous (63.8%), gastrointestinal (52.7%), cardiac (47.2%), pulmonary (38.8%), and neurological (11.1%) manifestations. At admission, 14/36 were IgM-positive, while 34/36 were IgG-positive. Follow-up revealed sequelae in two patients, including coronary aneurysms and ground-glass pulmonary opacities. Although MIS-C can be severe, most patients had favorable outcomes with proper treatment. Few long-term, organ-specific complications were observed, highlighting the importance of systematic monitoring to ensure full recovery. Full article

Background/Objectives: After pandemic of COVID-19, there were increased the incidence of Multisystem Inflammatory Syndrome in Children (MIS-C), as reported by the Centers for Disease Control and Prevention (CDC). However, it remains unclear which specific factors link MIS-C to COVID-19 following infection. This study aims to investigate the factors associated with MIS-C in children infected with COVID-19. Methods: A multicenter-matched case-control study was conducted across Chum Phae, Khon Kaen, and Srinagarind Hospitals, Thailand. We included patients under 21 years old from those hospitals from January 2021 to February 2024. The cases were patients diagnosed with MIS-C, while the controls had a history of COVID-19 infection but had not been diagnosed with MIS-C at least 3 months post-infection. The matching criteria for cases and controls, in a 1:2 ratio, included gender and age. The association between various factors and MIS-C was examined using conditional logistic regression. Results: A total of 34 MIS-C cases were matched with 68 controls. We found that antiviral therapy administered during COVID-19 infection was linked to a reduced risk of MIS-C development, with an adjusted odds ratio of 0.06 (95% CI: 0.02–0.20). However, this study found no association between COVID-19 vaccination and nutritional status in the development of MIS-C. Conclusions: The administration of antiviral treatment during COVID-19 infection was associated with a diminished incidence of MIS-C. Full article

Background: Cardiac involvement is a key prognostic factor in multisystem inflammatory syndrome in children (MIS-C), a rare but serious inflammatory condition that typically occurs 2–6 weeks after SARS-CoV-2 infection and is characterized by fever, systemic inflammation, and multiorgan involvement. Biomarkers may aid in early detection, severity assessment, and treatment stratification. Objective: To evaluate the diagnostic utility of established and emerging serum biomarkers in MIS-C, with an emphasis on cardiac dysfunction and disease severity. Methods: A systematic search was conducted in PubMed, Scopus, and Web of Science up to April 2025. Eligible studies included pediatric MIS-C cases with reported serum biomarkers. Meta-analyses were performed for NT-proBNP and troponin using random-effects models. Descriptive profiling was applied to emerging biomarkers. Subgroup comparisons were explored between severe and moderate MIS-C. Quality assessment followed the Newcastle–Ottawa Scale, and publication bias was assessed via funnel plots and Egger’s test. Results: A total of 67 studies were included, comprising >4000 pediatric MIS-C cases. NT-proBNP and troponin were consistently elevated (pooled means: 9697 pg/mL and 0.384 ng/mL, respectively), with a low risk of publication bias. Emerging biomarkers such as CXCL9, angiopoietin-2, and vitamin D revealed high inter-study variability but potential prognostic value. Subgroup analyses for selected studies (n = 5) suggested higher biomarker levels in severe MIS-C. Conclusions: NT-proBNP and troponin are robust indicators of cardiac injury in MIS-C. Emerging biomarkers show promise but require validation. Future studies should include copeptin and adopt standardized reporting to refine biomarker-guided management. Full article