Iren Tzotcheva

Background : Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but severe complication following SARS-CoV-2 infection. Early recognition and forecasting may support preparedness and clinical resource allocation. Objective : We aimed to model the temporal relationship between COVID-19 incidence and MIS-C cases using time series analysis. Materials and methods : We retrospectively analyzed data from 51 children with MIS-C (age 0–18 years) hospitalized in a single center between November 2020 and April 2021. A regression model with ARIMA(1,0,0) errors was applied to predict MIS-C cases based on weekly COVID-19 incidence in individuals aged 0–18 years. Results : The majority of children were male (n = 37, 72.5%) and older than 5 years (n = 40, 78%), with a mean age of 8.82 ± 4.16 years. Abdominal symptoms were predominant (n = 38, 74%), and nearly half experienced respiratory (n = 23, 45%) or cardiac (n = 26, 51%) involvement. The ARIMA model identified a lag of 5–6 weeks between COVID-19 cases and MIS-C incidence (R² = 0.41). A selection-aware Monte Carlo simulation confirmed the robustness of the model’s significant regressors when extrapolated beyond the original data period. Conclusion : The moderate predictive power of the ARIMA model supports the potential of syndromic surveillance to forecast MIS-C clusters, aiding early intervention. Larger datasets could further enhance prediction accuracy.

Background: Our goals were to find and grade children with multisystem inflammatory syndrome (MIS‐C) by clinical severity and the degree of different system involvement based on multivariate clinical laboratory data and identify the best predictors and scores for disease prognosis and risk stratification. Methods: We enrolled 51 patients with confirmed MIS‐C from a single center, and 34 general laboratory parameters and markers were included. Results: Using the K ‐means clustering method on kernel principal component analysis (K‐PCA) projections, we identified that our MIS‐C patients could be separated into three clusters. Children belonging to Cluster 3 have the highest levels of ferritin, LDH, ASAT, ALAT, GGT, total bilirubin, direct bilirubin, azotemia, urea, and creatinine, followed by Cluster 2. In contrast, Cluster 1 showed the lowest levels, p < 0.05. Children belonging to Clusters 3 and 2 also needed inotropic support significantly more frequently than Cluster 1 (30% and 10% vs 0%, Fisher exact test p = 0.04). Furthermore, respiratory distress was found only in patients of Clusters 2 and 3 ( p = 0.002). Regarding liver involvement, Clusters 2 and 3 more frequently had cholestasis (61% and 75% vs. 28%, p = 0.012), whereas Cluster 3 was more prominently characterized by an enlarged liver (44% vs. 0% and 5%, p = 0.004). Therefore, our clusters represent different grades, and liver and kidney involvement stages are graded by severity. From ROC curve analysis and several logistic regressions, we identified that age equal to or higher than 9 years old and ferritin levels higher than 470 ng/mL could help distinguish children with more severe kidney and liver involvement with a high probability (ROC AUC = 77 % , p = 0.03 and ROC AUC = 75 % , p = 0.04) approximately equal to the discriminatory potential of creatinine, urea, GGT and total bilirubin. Moreover, levels of LDH with a cutoff of 363 U/l could identify the children within Cluster 3 (ROC AUC = 80 % , p = 0.004). Conclusions: LDH and ferritin, as well as age into consideration, could help the clinical assessment of the underlying severity.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe post-infectious complication associated with SARS-CoV-2. Neurological manifestations occur in approximately one quarter of MIS-C cases, ranging from mild symptoms such as headache and photophobia to severe complications including seizures, encephalopathy, and stroke. This article provides a comprehensive review of the neurological aspects of MIS-C, incorporating evidence from the literature and a detailed case report of a 15-year-old male who presented with acute neurological symptoms, systemic inflammation, and multiorgan involvement. Four main pathophysiological mechanisms have been proposed to explain neurological involvement: cytokine-mediated neuroinflammation, blood–brain barrier disruption, autoimmune responses, and direct viral neuroinvasion. Neuroimaging and EEG findings often support encephalopathic processes, while laboratory and immunological profiles indicate a hyperinflammatory state. The present case also highlights a potential link between severe hyponatremia and neurological complications. Management strategies—such as immunomodulation, anticoagulation, supportive therapy, and neuroprotective interventions—are discussed in this context. The prognosis for MIS-C patients with neurological involvement varies, with severe cases requiring long-term monitoring. This review underscores the importance of early neurological assessment in MIS-C to guide treatment and improve outcomes.

A hydropneumothorax is an uncommon complication of pneumonia, particularly in pediatric patients, and typically arises secondary to conditions such as malignancies, esophageal-pleural fistula, thoracic trauma, or thoracocentesis. While pneumothorax is rarely reported in adults with COVID-19 and is even less common in children, isolated cases have been noted in those with Multisystem Inflammatory Syndrome in Children (MIS-C). A recent alert has also been issued about increased Group A Streptococcus (GAS) infections in Europe. Against this background, the primary aim of this case report is to describe a rare and severe complication of pneumonia in a previously healthy child with MIS-C and a positive throat culture for GAS.

Background and objectives: Multisystem inflammatory syndrome in children (MIS-C) poses challenges to the healthcare system, especially with frequent heart involvement. The current retrospective observational study aims to summarize the type and degree of cardiovascular involvement in children with MISC and to find possible associations between laboratory, inflammatory, and imaging abnormalities and the predominant clinical phenotype using a cluster analysis. Material and methods: We present a retrospective observational single-center study including 51 children meeting the MIS-C criteria. Results: Fifty-three percent of subjects presented with at least one sign of cardiovascular involvement (i.e., arterial hypotension, heart failure, pericardial effusion, myocardial dysfunction, pericarditis without effusion, myocarditis, coronaritis, palpitations, and ECG abnormalities). Acute pericarditis was found in 30/41 of the children (73%) assessed using imaging: 14/30 (46.7%) with small pericardial effusion and 16/30 (53.3%) without pericardial effusion. The levels of CRP were significantly elevated in the children with pericarditis (21.6 ± 13 mg/dL vs. 13.9 ± 11 mg/dL, p = 0.035), and the serum levels of IL-6 were higher in the children with small pericardial effusion compared to those without (191 ± 53 ng/L vs. 88 ± 27 ng/L, p = 0.041). Pericarditis with detectable pericardial effusion was significantly more frequent in the female vs. male subjects, 72% vs. 30% (p = 0.007). The hierarchical clustering analysis showed two clusters: Cluster 1 includes the children without cardiovascular symptoms, and Cluster 2 generalizes the MIS-C children with mild and severe cardiovascular involvement, combining pericarditis, myocarditis, heart failure, and low blood pressure. Also, subjects from Cluster 2 displayed significantly elevated levels of fibrinogen (5.7 ± 0.3 vs. 4.6 ± 0.3, p = 0.03) and IL-6 (158 ± 36 ng/mL vs. 66 ± 22 ng/mL, p = 0.032), inflammatory markers suggestive of a cytokine storm. Conclusions: Our results confirm that children with oligosymptomatic MIS-C or those suspected of long COVID-19 should be screened for possible cardiological involvement.

Introduction: Acute upper respiratory tract infections (AURTIs) are associated with a significant burden on society attributed to medical care and loss of productivity. Novel therapies that are able to shorten disease duration, while providing symptom relief and being well tolerated, are an unmet medical need. Aim: The main objective of this trial was to investigate the efficacy and safety of Aviron Rapid, a dietary supplement containing andrographolide, proprietary spirulina, and humic acid, in the management of AURTIs in adolescents and children. Materials and methods: This randomized, double-blind, placebo-controlled trial was conducted between January 2020 and March 2020 in 85 general practitioner practices in Bulgaria. Adolescents (13–17 years) and children (5–12 years) with a clinical diagnosis of AURTI were randomly assigned to receive standard symptomatic therapy + Aviron Rapid or placebo for 5 and 7 days, respectively. The primary endpoints of this trial were the number (and percentage) of clinically recovered patients and the mean disease duration. Results: In total, 380 adolescents and 401 children were enrolled in 2 age cohorts and randomly assigned to treatment with Aviron Rapid or placebo. The percentage of patients meeting the criteria for clinical recovery was significantly higher in the Aviron Rapid group compared with the placebo group from 24 and 48 hours after initiation of treatment in adolescents and children, respectively. Aviron Rapid treatment significantly reduced the duration of disease, of fever, and of antipyretics intake in both adolescents and children. When compared to placebo, a significantly higher percentage of adolescents and children on Aviron Rapid achieved a persistent decrease in temperature of less than 37°C as soon as 24 hours after starting treatment. Overall, a low number of adverse events was reported and no major differences in the incidence of individual adverse events were observed between the two treatment groups in both cohorts. Conclusions: This clinical trial demonstrated the efficacy of Aviron Rapid in the management of acute upper respiratory tract infections in adolescents and children. Aviron Rapid treatment rapidly increased the number of clinically recovered patients and reduced overall disease duration and duration of symptoms, in particular fever, while being well tolerated. Trial registration: International Standard Randomised Controlled Trial Number (ISRCTN) 12221500. Retrospectively registered on 29 March 2022. [https://doi.org/10.1186/ISRCTN12221500]

Background: Digestive symptoms and gastrointestinal issues in children with coronavirus 2019 disease (COVID-19) and Multisystem Inflammatory Syndrome in Children (MIS-C) are commonly reported in pediatric studies from different countries. Our retrospective observational study aimed to summarize the main digestive symptoms and objective data on gastrointestinal involvement in children with MIS-C. Methods: We present the clinical, laboratory, and imaging data of 51 children with MIS-C hospitalized in a single center from 25 November 2020 to 24 April 2021, focusing on gastrointestinal involvement. Results: A total of 46/51 children (90.2%) reported at least one abdominal symptom (abdominal pain (86%, N = 44), vomiting, nausea, diarrhea), predominantly at presentation. Most children were older than 5 years (N = 40, 78%), predominated by the male sex (N = 37, 72.5%), and with a mean age of 8.82 ± 4.16 years. We found a tendency for lymphopenia, neutrophilia, and higher levels of CRP, d-dimer, and ferritin in MIS-C patients with abdominal pain (R-squared 0.188, F-statistic vs. constant model: 11.9, p-value = 0.00122, 20% explanation of variation with p = 0.001). We found a statistically significant linear relationship (regression) between neutrophile percentage (NEU%) and hospital stay and a tendency for elevated transaminases to be more frequent in older children (27.3% under 5 years and 65% over 5 years; p = 0.0583). We found no significant associations between digestive symptoms and age or the predominant SARS-CoV-2 variant. Conclusions: Most of our MIS-C patients presented with abdominal pain, usually along with other GI symptoms, which could be applied in clinical practice to MIS-C in children visiting the emergency room with abdominal pain and evidence of recent COVID-19 contact or infection. Further information from larger cohorts of MIS-C patients is needed to better understand the epidemiology of gastrointestinal involvement in these patients.

(1) Background: Currently, multisystem inflammatory syndrome in children (MIS-C) is diagnosed based on clinical symptoms and laboratory findings of inflammation in the body. Once MIS-C is diagnosed, children will need to be followed over time. The imaging modalities most commonly used in the evaluation of patients with MIS-C include radiographs, ultrasound (US), and computed tomography (CT). Our study aims to summarise the literature data for the main gastrointestinal and pulmonary imaging features in children diagnosed with MIS-C and to share a single-centre experience. (2) Methods: We present the imaging findings in a cohort of 51 children diagnosed with MIS-C, admitted between December 2020 and February 2022. Imaging studies include chest and abdominal radiographs, thoracic, abdominal, and neck US and echocardiography (ECHO), and CT of the chest, abdomen, and pelvis. (3) Results: In accordance with the results in other studies, our observations show predominantly gastrointestinal involvement (GI) with ascites (33/51, 65%) and lymphadenopathy (19/51, 37%), ileitis or colitis (18/51, 35%), some cases of splenomegaly (9/51, 18%), hepatomegaly (8/51, 16%), and a few cases of renal enlargement (3/51, 6%) and gallbladder fossa oedema/wall thickening (2/51, 4%). Most common among the thoracic findings are posterior–basal consolidations (16/51, 31%), pleural effusion (14/51, 27%), and ground-glass opacities (12/51, 24%). We also register the significant involvement of the cardiovascular system with pericarditis (30/51, 58%), pericardial effusion (16/51, 31%), and myocarditis (6/51, 12%). (4) Conclusions: Radiologists should be aware of those imaging findings in order to take an important and active role not only in applying an accurate diagnosis, but also in the subsequent management of children with MIS-C. Radiological findings are not the primary diagnostic tool, but can assist in the evaluation of the affected systems and guide treatment.

Нuman bocaviruses (hBoVs) are often associated with acute respiratory infections (ARIs). Information on the distribution and molecular epidemiology of hBoVs in Bulgaria is currently limited. The objectives of this study were to investigate the prevalence and genetic characteristics of hBoVs detected in patients with ARIs in Bulgaria. From October 2016 to September 2019, nasopharyngeal/oropharyngeal swabs were prospectively collected from 1842 patients of all ages and tested for 12 common respiratory viruses using a real-time RT-PCR. Phylogenetic and amino acid analyses of the hBoV VP1/VP2 gene/protein were performed. HBoV was identified in 98 (5.3) patients and was the 6^th most prevalent virus after respiratory-syncytial virus (20.4), influenza A(H1N1)pdm09 (11.1), A(H3N2) (10.5), rhinoviruses (9.9), and adenoviruses (6.8). Coinfections with other respiratory viruses were detected in 51 of the hBoV-positive patients. Significant differences in the prevalence of hBoVs were found during the different study periods and in patients of different age groups. The detection rate of hBoV was the highest in patients aged 04 years (6.9). In this age group, hBoV was the only identified virus in 9.7, 5.8, and 1.1 of the children diagnosed with laryngotracheitis, bronchiolitis, and pneumonia, respectively. Among patients aged 5 years, hBoV was detected as a single agent in 2.2 of cases of pneumonia. Phylogenetic analysis showed that all Bulgarian hBoV strains belonged to the hBoV1 genotype. A few amino acid substitutions were identified compared to the St1 prototype strain. This first study amongst an all-age population in Bulgaria showed a significant rate of hBoV detection in some serious respiratory illnesses in early childhood, year-to-year changes in the hBoV prevalence, and low genetic variability in the circulating strains.

SARS-CoV-2 infection may precede and cause various autoimmune and inflammatory diseases, including multisystem inflammatory syndrome in children (MIS-C). Therefore, we aimed to observe the clinical presentation and laboratory, instrumental and other constellations in children with MIS-C, including liver involvement. We present the outcomes from a single-center prospective observational study in which 89 children was included (60 with proven COVID-19, 10 symptomatic with confirmed COVID-19 contact and 19 diagnosed with MIS-C). Laboratory, instrumental, immunological, and clinical investigations were performed. Only 12% (n = 4) from the COVID-19 group (except the ICU cases), we found elevated AST and/or ALT (up to 100). All of the children with elevated transaminase were overweight or obese, presenting along with moderate COVID-19 pneumonia. The majority of children with MIS-C showed typical laboratory constellations with higher levels of IL-6 (120.36 ± 35.56 ng/mL). About half of the children in the MIS-C group (52%, n = 11) showed elevated transaminases. Eleven children (57.9%) presented with abdominal pain, eight (42.1%) with ascites, two (10.5%) with hepatosplenomegaly, and four (21.1%) with symptoms such as diarrhea. Mesenteric lymphadenitis was observed more often in patients with elevated LDH (327.83 ± 159.39, p = 0.077). Ascites was associated with lymphopenia (0.86 ± 0.80, p = 0.029) and elevated LDH. Hepato-splenomegaly was also more frequent in children with lymphopenia (0.5 ± 0.14, p = 0.039), higher troponin (402.00 ± 101.23, p = 0.004) and low ESR. Diarrhea was more frequent in patients with lower CRP (9.00 ± 3.44 vs. 22.25 ± 2.58, p = 0.04), and higher AST and ALT (469.00 ± 349.59 vs. and 286.67 ± 174.91, respectively, p = 0.010), and D-dimer (4516.66 ± 715.83, p = 0.001). Our data suggest that the liver can also be involved in MIS-C, presenting with typical laboratory and instrumental outcomes.