Cardiac Involvement in Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) in Poland.

Multisystem inflammatory syndrome in children (MIS-C) is an immune-mediated complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cardiovascular system is commonly involved. Acute heart failure (AHF) is the most severe complication of MIS-C, leading to cardiogenic shock. The aim of the study was to characterise the course of MIS-C with a focus on cardiovascular involvement, based on echocardiographic (echo) evaluation, in 498 children (median age 8.3 years, 63% boys) hospitalised in 50 cities in Poland. Among them, 456 (91.5%) had cardiovascular system involvement: 190 (48.2%) of patients had (most commonly atrioventricular) valvular insufficiency, 155 (41.0%) had contractility abnormalities and 132 (35.6%) had decreased left ventricular ejection fraction (LVEF < 55%). Most of these abnormalities improved within a few days. Analysis of the results obtained from two echo descriptions (a median of 5 days apart) revealed a >10% increase in LVEF even in children with primarily normal LVEF. Lower levels of lymphocytes, platelets and sodium and higher levels of inflammatory markers on admission were significantly more common among older children with contractility dysfunction, while younger children developed coronary artery abnormality (CAA) more often. The incidence of ventricular dysfunction might be underestimated. The majority of children with AHF improved significantly within a few days. CAAs were relatively rare. Children with impaired contractility as well as other cardiac abnormalities differed significantly from children without such conditions. Due to the exploratory nature of this study, these findings should be confirmed in further studies.

COVID-19 mRNA BNT162b2 vaccine immunogenicity among children with a history of paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS).

We conducted a prospective cohort study of 20 patients with a history of paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS group, median age seven years, 70% male) and 34 healthy controls without such a history (CONTROL group, median age eight years, 38% male) aged 5-12 years, to assess the immunogenicity of Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine (Comirnaty®). Patients received two doses of COVID-19 mRNA BNT162b2 vaccine (10 ug/dose) 21 days apart. Pre-vaccine anti-S SARS-CoV-2 IgG antibodies were measured on the day of the first dose and at the median of 23 days after the second dose. The study was conducted during the COVID-19 wave dominated by the Omicron variant of the virus. Anti-NCP SARS-CoV-2 IgG antibodies were measured twice to evaluate incidents of infection during the study period. Pre-vaccine quantification of both types of antibodies allowed us to differentiate patients into COVID-19 naive and previously infected in order to compare hybrid immunity with vaccine-induced immunity. Before vaccination, anti-S IgG serum geometric mean concentration (GMC) was 61.17 BAU/ml in the PIMS group and 24.97 in the CONTROL group, while post-vaccination GMC was 3879.14 BAU/ml and 3704.87 BAU/ml, respectively, and did not significantly differ between the groups. Hybrid immunity (regardless of PIMS history) resulted in a higher concentration of SARS-CoV-2 anti-S antibodies after vaccination. Four (20%) of the children in the PIMS group and 11 (32%) in the CONTROL group got infected with SARS-CoV-2 during the study period, yet all of them asymptomatically, and this event has not significantly altered post-vaccination anti-S titers. In conclusion, COVID-19 vaccination was highly immunogenic in children, including those with a history of PIMS-TS; hybrid immunity overperforms vaccine-induced immunity in terms of serological response in children. However, vaccination effectiveness in preventing SARS-CoV-2 infections in children should be further evaluated.

COVID-19 mRNA BNT162b2 vaccine safety and B-cell and T-cell reactogenicity among children with a history of paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS) - preliminary study

To assess the safety of Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine (Comirnaty®) among patients with the anamnesis of paediatric inflammatory syndrome temporally associated with COVID-19 (PIMS-TS), we conducted a prospective cohort study of 21 patients with history of PIMS (PIMS group, median age 7.4 years, 71% male) and 71 healthy controls without such an anamnesis (CONTROL group, median age 9.0 years, 39% male) aged 5–18 years. Among them, 85 patients (all PIMS patients and 64 CONTROL patients) completed the two dose schedule of vaccination administered 21 days apart and 7 children in the CONTROL group received a single, age appropriate dose of a COVID-19 mRNA BNT162b2 vaccine during the study period. The frequency and character of reported adverse events (AEs) after each dose and results of flow cytometry (FC) 3 weeks after a second dose were compared between those groups. COVID-19 mRNA BNT162b2 vaccine safety profile was very good and comparable in both groups. No severe AEs were observed. 30% of all patients reported some general AE after any vaccine dose and 46% - some local AE. Frequency of reported AEs did not differ between groups except for local hardening at injection site, more common in PIMS group (20% vs 4% after any vaccine dose, p = 0,02). All AEs were benign, general AEs lasted up to 5 days and localised - up to 6 days after a vaccine dose. COVID-19 mRNA BNT162b2 vaccine did not induce any PIMS-like symptoms in any patient. We did not observe any significant T cells or B cells subset abnormalities in the PIMS group compared to the CONTROL group three weeks after a second dose except for terminally differentiated effector memory T cells that were higher in PIMS group (p < 0.0041). To sum up COVID-19 mRNA BNT162b2 vaccine in children with PIMS-TS was safe. Further studies are required to support our findings.

COVID-19 mRNA BNT162b2 vaccine safety and B-cell and T-cell reactogenicity among children with a history of paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS) - preliminary study.

To assess the safety of Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine (Comirnaty®) among patients with the anamnesis of paediatric inflammatory syndrome temporally associated with COVID-19 (PIMS-TS), we conducted a prospective cohort study of 21 patients with history of PIMS (PIMS group, median age 7.4 years, 71% male) and 71 healthy controls without such an anamnesis (CONTROL group, median age 9.0 years, 39% male) aged 5-18 years. Among them, 85 patients (all PIMS patients and 64 CONTROL patients) completed the two dose schedule of vaccination administered 21 days apart and 7 children in the CONTROL group received a single, age appropriate dose of a COVID-19 mRNA BNT162b2 vaccine during the study period. The frequency and character of reported adverse events (AEs) after each dose and results of flow cytometry (FC) 3 weeks after a second dose were compared between those groups. COVID-19 mRNA BNT162b2 vaccine safety profile was very good and comparable in both groups. No severe AEs were observed. 30% of all patients reported some general AE after any vaccine dose and 46% - some local AE. Frequency of reported AEs did not differ between groups except for local hardening at injection site, more common in PIMS group (20% vs 4% after any vaccine dose, p = 0,02). All AEs were benign, general AEs lasted up to 5 days and localised - up to 6 days after a vaccine dose. COVID-19 mRNA BNT162b2 vaccine did not induce any PIMS-like symptoms in any patient. We did not observe any significant T cells or B cells subset abnormalities in the PIMS group compared to the CONTROL group three weeks after a second dose except for terminally differentiated effector memory T cells that were higher in PIMS group (p < 0.0041). To sum up COVID-19 mRNA BNT162b2 vaccine in children with PIMS-TS was safe. Further studies are required to support our findings.

COVID-19 mRNA Vaccine Tolerance and Immunogenicity in Hematopoietic Stem Cell Transplantation Recipients Aged 5-11 Years Old-Non-Randomized Clinical Trial.

The SARS-CoV-2 pandemic had a devastating impact on the world's population in the years 2020−2022. The rapid development of vaccines enabled a reduction in the mortality and morbidity of COVID-19, but there are limited data about their effects on immunocompromised children. The aim of this prospective study was to evaluate the safety and efficacy of the mRNA BNT162b2 (Pfizer/Biontech) vaccine in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Material and methods: Two cohorts of 34 children after allo-HSCT and 35 healthy children aged 5−11 years were vaccinated with two doses of the mRNA BNT162b2 (10 µg) vaccine. All children were evaluated for adverse effects with electronic surveys and the immunogenicity of the vaccine was assessed with anti-SARS-CoV-2 IgG titer measurements. Results: All reported adverse events (AEs) were classified as mild. The most common AE was pain at the injection site. All the other AEs (both local and systemic) were rarely reported (<15% patients). Both groups showed a similar response in anti-SARS-CoV-2 IgG production. Patients after allo-HSCT that were undergoing immunosuppressive treatment presented a poorer immunological response than patients off of treatment. Time since HSCT, patient age, lymphocyte count, and total IgG concentration did not correlate with initial/post-vaccination anti-SARS-CoV-2 IgG titers. Most patients who were eligible for a third dose of the vaccine had an excellent humoral response observed after two vaccine doses. Conclusions: The COVID-19 mRNA BNT162b2 vaccine is very well tolerated and highly immunogenic in 5−11-year-old children after HSCT. Children >2 years of age after HSCT who did not receive immunosuppressive treatment presented excellent antibody production after two doses of the vaccine, but children on immunosuppression may require a more intense vaccination schedule.

A tendency to worse course of multisystem inflammatory syndrome in children with obesity: MultiOrgan Inflammatory Syndromes COVID-19 related study

Background A new disease entity called multisystem inflammatory syndrome in children (MIS-C) is a rare consequence of COVID-19 infection. The pathophysiology and risk factors of MIS-C are still unclear, and the clinical manifestation ranges from milder forms to cases needing intensive care unit treatment. Based on available data, obesity is linked to pro-inflammatory stimulation. Moreover, several studies showed that obesity could play a role in COVID-19 severity and its comorbidities among the adult and children’s populations. This study aimed to investigate the influence of overweightedness/obesity in childhood for the course of MIS-C in Poland. Methods This study presented data from the national MultiOrgan Inflammatory Syndromes COVID-19 Related Study (MOIS-CoR) collected between 4 March 2020 and 20 February 2021. Of the 371 patients that met the Polish MIS-C criteria, 306 were included for further analysis. Results Children who are obese (OB with body mass index (BMI) ≥95th percentile) and overweight (OV with BMI ≥85th percentile but <95th percentile) (28 and 49 patients, respectively) represented 25.1% (n=77) of all recruited patients. Complete recovery at the time of discharge presented in 93% of normal body weight (NW) participants and 90% of OV children (p>0.05). Among OB children, 76% recovered fully, which differed from the NW group (p=0.01). Calculated odds ratio (OR) of incomplete recovery for OB children was 4.2. Irrespective of body weight, there were no differences (p>0.05) in the length of hospitalization and the duration of symptoms (for OB, 13 and 16.5 days;for OV and NW, 10 and 14 days, respectively), as well as in the frequency of cardiovascular abnormalities, necessity of oxygen therapy (OB, 26.9%;OV, 23.9%;and NW, 20.7%), and intravenous immunoglobulin and glucocorticosteroid (GCS) treatment. Conclusion The higher risk of incomplete recovery and observed tendency toward a worsening course of MIS-C in patients with obesity suggest the need for further studies to confirm and understand our findings.

Clinical characteristics of children with MIS-C fulfilling classification criteria for macrophage activation syndrome

Background Macrophage activation syndrome (MAS) is a potentially life-threatening complication of various inflammatory disorders, including multisystem inflammatory syndrome in children (MIS-C). MIS-C refractory to treatment should raise suspicion of MAS, which can be fatal if a definitive diagnosis is delayed. Unfortunately, there is a lack of data on MAS in children with MIS-C. Objective Our study aims to analyze the risk factors for the development of MAS in MIS-C, its clinical course and response to treatment, and identify predictive factors for pediatric intensive care. Material and methods We analyzed data from the Polish MIS-C registry of the MultiOrgan Inflammatory Syndromes COVID-19 Related Study. Patients were diagnosed according to the WHO MIS-C definition and treated according to national guidelines (Polish Pediatric Society) based on international consensus. MAS definition was based on 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis. Results Two-hundred and seventy four children met the study inclusion criteria. Fifty-nine patients fulfilled MAS classification criteria, nine of which required admission to the pediatric intensive care unit (PICU). MIS-C patients with MAS were significantly older than patients without MAS (median 11.2 vs. 8.1 years). Multivariable analysis showed that age, symptoms characteristic of atypical Kawasaki disease, and skin erosions were significant factors associated with MAS in MIS-C patients. Analysis of laboratory parameters showed that on admission, MIS-C patients with MAS had significantly lower median lymphocyte and platelet counts, albumin and sodium levels, and higher median levels of C-reactive protein, procalcitonin, ferritin, D-dimers, triglycerides, serum creatinine, urea, and γ-glutamyl transpeptidase, and neutrophil count. Multivariate analysis showed that higher procalcitonin, ferritin, and fibrinogen levels at admission were predictive of MAS. Only elevated troponin level was a factor indicating a requirement of PICU hospitalization for children with MAS. MIS-C patients fulfilling MAS criteria were treated more often with intravenous immunoglobulins and steroids than children without MAS. Children with MAS more often required mechanical ventilation. None of the patients required biological agents. Conclusions The clinical course of MAS in MIS-C seems milder, treatment less aggressive, and the prognosis better than expected based on the current knowledge on MAS complicating other rheumatological diseases.

Use of broad-spectrum antibiotics in children diagnosed with multisystem inflammatory syndrome temporarily associated with SARS-CoV-2 infection in Poland: the MOIS-CoR study.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) is the result of an immune response triggered by a previous exposure to SARS-CoV-2. The clinical presentation of MIS-C overlaps with other life-threatening bacterial infections, in which antimicrobials are the mainstay therapy. The aim of study was to describe the use of antibiotics in children with MIS-C in Poland. METHODS: The analysis of 345 children reported from 42 Polish cities to the national MultiOrgan Inflammatory Syndromes COVID-19 Related Study (MOIS-CoR Study) from June 2020 to April 2021. RESULTS: At least one antibiotic was used in 310 (90%) children, mainly third-generation cephalosporin (251/310). Broad-spectrum antibiotics were used in 258 (75%) children and 224 (87%) received this treatment for more than 3 days. Concentrations of serum procalcitonin >2 µg/l and the presence of lower respiratory symptoms were associated with increased odds of receiving any antibiotic. CONCLUSION: Although bacterial infections in patients with MIS-C are uncommon, we show that MIS-C poses a challenge to clinicians who are faced with the decision to start, continue, or stop antimicrobial therapy. Antibiotic stewardship in patients with MIS-C should be improved to ensure that likely pathogens are treated and that antimicrobials are stopped when bacterial infections are excluded and the diagnosis of MIS-C is made.

Distinct characteristics of multisystem inflammatory syndrome in children in Poland.

During the winter months of 2020/2021 a wave of multisystem inflammatory syndrome in children (MIS-C) emerged in Poland. We present the results of a nationwide register aiming to capture and characterise MIS-C with a focus on severity determinants. The first MIS-C wave in Poland was notably high, hence our analysis involved 274 children. The group was 62.8% boys, with a median age of 8.8 years. Besides one Asian, all were White. Overall, the disease course was not as severe as in previous reports, however. Pediatric intensive care treatment was required for merely 23 (8.4%) of children, who were older and exhibited a distinguished clinical picture at hospital admission. We have also identified sex-dependent differences; teenage boys more often had cardiac involvement (decreased ejection fraction in 25.9% vs. 14.7%) and fulfilled macrophage activation syndrome definition (31.0% vs. 15.2%). Among all boys, those hospitalized in pediatric intensive care unit were significantly older (median 11.2 vs. 9.1 years). Henceforth, while ethnicity and sex may affect MIS-C phenotype, management protocols might be not universally applicable, and should rather be adjusted to the specific population.

Takotsubo syndrome as a cardiac manifestation of multisystem inflammatory syndrome in children.

Cases of severe heart damage in patients presenting with multisystem inflammatory syndrome in children are one of the most intriguing phenomena during the coronavirus disease of 2019 pandemic. The pathophysiology of myocardial changes in the course of this syndrome has not been fully understood yet. We present a case of a child with multisystem inflammatory syndrome in children and with cardiac changes corresponding to Takotsubo syndrome.

Distinct characteristics of multisystem inflammatory syndrome in children in Poland

During the winter months of 2020/2021 a wave of multisystem inflammatory syndrome in children (MIS-C) emerged in Poland. We present the results of a nationwide register aiming to capture and characterise MIS-C with a focus on severity determinants. The first MIS-C wave in Poland was notably high, hence our analysis involved 274 children. The group was 62.8% boys, with a median age of 8.8 years. Besides one Asian, all were White. Overall, the disease course was not as severe as in previous reports, however. Pediatric intensive care treatment was required for merely 23 (8.4%) of children, who were older and exhibited a distinguished clinical picture at hospital admission. We have also identified sex-dependent differences;teenage boys more often had cardiac involvement (decreased ejection fraction in 25.9% vs. 14.7%) and fulfilled macrophage activation syndrome definition (31.0% vs. 15.2%). Among all boys, those hospitalized in pediatric intensive care unit were significantly older (median 11.2 vs. 9.1 years). Henceforth, while ethnicity and sex may affect MIS-C phenotype, management protocols might be not universally applicable, and should rather be adjusted to the specific population.

Pediatric Inflammatory Multisystem Syndrome (PIMS) Did Occur in Poland during Months with Low COVID-19 Prevalence, Preliminary Results of a Nationwide Register.

Pediatric inflammatory multisystem syndrome (PIMS) is a new entity in children, likely associated with previous coronavirus disease 19 (COVID-19) infection. Most of the reports about PIMS come from countries particularly hit by the COVID-19 pandemic. Our aim was to investigate the nature of inflammatory syndromes in Poland (country with low COVID-19 prevalence) and to perceive the emergence of PIMS in our country. On 25 May 2020, we launched a nationwide survey of inflammatory syndromes in children for retrospective (since 4 March 2020) and prospective data collection. Up to 28 July, 39 reported children met the inclusion criteria. We stratified them according to age (<5 and ≥ 5 years old) and COVID-19 status. The majority of children had clinical and laboratory features of Kawasaki disease, probably non-associated with COVID-19. However, children ≥5 years of age had PIMS characteristics, and nine children had COVID-19 confirmation. This is, to our knowledge, the first report of the PIMS register from a country with a low COVID-19 prevalence, and it proves that PIMS may emerge in any area involved in the COVID-19 pandemic. In a context of limited COVID-19 testing availability, other risk factors of PIMS, e.g., older age, should be considered in the differential diagnosis of inflammatory syndromes in children.

Pediatric Inflammatory Multisystem Syndrome (PIMS) Did Occur in Poland during Months with Low COVID-19 Prevalence, Preliminary Results of a Nationwide Register

Pediatric inflammatory multisystem syndrome (PIMS) is a new entity in children, likely associated with previous coronavirus disease 19 (COVID-19) infection. Most of the reports about PIMS come from countries particularly hit by the COVID-19 pandemic. Our aim was to investigate the nature of inflammatory syndromes in Poland (country with low COVID-19 prevalence) and to perceive the emergence of PIMS in our country. On 25 May 2020, we launched a nationwide survey of inflammatory syndromes in children for retrospective (since 4 March 2020) and prospective data collection. Up to 28 July, 39 reported children met the inclusion criteria. We stratified them according to age (<5 and ≥5 years old) and COVID-19 status. The majority of children had clinical and laboratory features of Kawasaki disease, probably non-associated with COVID-19. However, children ≥5 years of age had PIMS characteristics, and nine children had COVID-19 confirmation. This is, to our knowledge, the first report of the PIMS register from a country with a low COVID-19 prevalence, and it proves that PIMS may emerge in any area involved in the COVID-19 pandemic. In a context of limited COVID-19 testing availability, other risk factors of PIMS, e.g., older age, should be considered in the differential diagnosis of inflammatory syndromes in children.