Three-Dimensional Echocardiography and Global Longitudinal Strain in Follow-Up After Multisystem Inflammatory Syndrome in Children: Six-Month, Single-Center, Prospective Study.

OBJECTIVE: To assess the potential long-term cardiac effects after multisystem inflammatory syndrome in children (MIS-C) with cardiovascular involvement in the acute phase. STUDY DESIGN: Our prospective study involved children consecutively diagnosed with MIS-C between October 2020 and February 2022 and followed 6 weeks and 6 months after the disease. In patients with severe cardiac involvement during the acute phase, an additional check-up after 3 months was scheduled. In all patients at all check-ups, 3-dimensional echocardiography and global longitudinal strain (GLS) were used to assess ventricular function. RESULTS: The study enrolled 172 children aged 1-17 years (median, 8 years). The means of ejection fraction (EF) and GLS for both ventricles were within normal limits after 6 weeks with no relationship with initial severity: left ventricular EF (LVEF) 60% (59%-63%), LV GLS -21.08% (-18.63% to -23.2%), right ventricular (RV) EF 64% (62%-67%), and RV GLS -22.8% (-20.5% to -24.5%). Further, statistically significant improvement of LV function was observed after 6 months-LVEF 63% (62%-65%) and LV GLS -22.55% (-21.05% to -24.25%; P < .05); however, RV function remained unchanged. The group with severe cardiac involvement showed LV function recovery pattern with no significant improvement between 6 weeks and 3 months after MIS-C, while still improving between 3 and 6 months after discharge. CONCLUSIONS: LV and RV function is within normal limits 6 weeks after MIS-C regardless of severity of cardiovascular involvement; LV function improves further between 6 weeks and 6 months after the disease. The long-term prognosis is optimistic with full recovery of cardiac function.

Clinical profile and management of patients with pediatric inflammatory multisystem syndrome - temporally associated with SARS-CoV-2 - single-center experience

Introduction and aim. Pediatric Inflammatory Multisystem Syndrome (PIMS-TS) is a new condition that has emerged in children during the COVID-19 pandemic. Many clinical signs and symptoms resemble those found in Kawasaki disease (KD). Material and methods. The following data were considered: clinical presentation, comorbidities, laboratory findings, abnormalities in additional tests, exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the child and his family members, applied treatment and return to full health. Results. In the presented study nineteen children were analyzed. Fever was a universal finding in our group and it's mean duration was 7 days (range 5-9). Other common symptoms included abdominal pain and severe weakness (in 89.5%), rash and conjunctivitis (in 84.2%), vomiting (in 73.7%) and mucous membrane involvement (in 63.2%). In nearly half of cases, echocardiography revealed fluid in the pericardial sac and left ventricular systolic dysfunction (in 52.6% and 47.4% respectively). 21.1% of patients had coronary artery abnormalities. 26, 3% of the children required treatment with dopamine and/or milrinone. In 15.7% ICU admissions and assisted ventilation was necessary. No deaths were recorded. Conclusion. One should bear in mind that PIMS-TS can mimic KD, appendicitis and meningitis, which may pose a diagnostic challenge. © 2022 Publishing Office of the University of Rzeszow. All Rights Reserved.

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.

Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS) and Serous Effusions in a Child With Severe Hypoalbuminemia: A Case Report.

In April 2020, Pediatric Inflammatory Multisystem Syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 or SARS­CoV­2 (PIMS-TS) was described for the first time in children. Since then, many countries have registered hundreds of cases with clinical similarities to Kawasaki disease. We report the case of a five-year-old boy diagnosed with PIMS-TS who presented myocarditis with serous effusions (pleurisy, ascites, pericarditis) due to severe hypoalbuminemia. This case sheds light on the importance of hypoalbuminemia in evaluating the severity of PIMS-TS and preventing its complications. The patient was successfully treated with intravenous immunoglobulins and oral prednisone.

SARS-CoV-2 variants and the risk of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 among children in Germany.

PURPOSE: To investigate the relationship between the risk of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in children and the predominance of different SARS-CoV-2 variants of concern (VOC) over time. METHODS: In relation to the Alpha, Delta, and Omicron VOC phases of the pandemic, the risk of developing PIMS-TS was calculated by analyzing data for rtPCR-confirmed SARS-CoV-2 infections reported to the German statutory notification system, along with data captured by a separate, national PIMS-TS registry. Both overall infection rates and age group-specific ratios of PIMS-TS during the different pandemic phases were calculated using the Alpha period as the baseline. RESULTS: The PIMS-TS rate changed significantly over time. When the Alpha VOC was dominant [calendar week (CW) 11 in March-CW 31 in August 2021], the PIMS-TS rate was 6.19 [95% confidence intervals (95% CI) 5.17, 7.20]. When Delta prevailed (CW 32 in August 2021-CW 4 in January 2022), the rate decreased to 1.68 (95% CI 1.49, 1.87). During the Omicron phase (CW 5 in January-CW 16 in April 2022), the rate fell further to 0.89 (95% CI 0.79, 1.00). These changes correspond to a decreased PIMS-TS rate of 73% (rate ratio 0.271, 95% CI 0.222; 0.332) and 86% (rate ratio 0.048, 95% CI 0.037; 0.062), respectively, in comparison to the Alpha period. Rate ratios were nearly identical for all age groups. CONCLUSION: The data strongly suggest an association between the risk for PIMS-TS and the prevailing VOC, with highest risk related to Alpha and the lowest to Omicron. Given the uniformity of the decreased risk across age groups, vaccination against SARS-CoV-2 does not appear to have a significant impact on the risk of children developing PIMS-TS.

Miscellaneous causes of abdominal pain

FAPDs (Functional Abdominal Pain Disorders) are the most common cause of chronic abdominal pain but are largely diagnoses of exclusion. More specific, but much less common, causes of acute and chronic abdominal pain include COVID-19 (PIMS-TS), Helicobacter pylori infection, Yersinia spp. Infection and Familial Mediterranean Fever. © Springer Nature Switzerland AG 2022. All rights reserved.

Kawasaki-like disease related to COVID-19. Perioperative management of a pediatric case

The recently identified COVID-19-related Kawasaki-like disease has been considered one of the phenotypes of the cardiovascular manifestations of the Pediatric Multisystem Inflammatory Syndrome associated with SARS-CoV-2 (PIMS-TS), which stands out for few respiratory symptoms and multiple manifestations cardiovascular, the most important being dilation and eventual coronary aneurysms associated or not with cardiogenic shock. The literature is scarce, so perioperative management is challenging for the anesthesiology team. We present the case of an infant with severe cardiovascular manifestations as a result of this disease that required anesthetic interventions to perform a plethysmography and amputation of his lower extremity. The article describes the most relevant considerations in the perioperative management of patients with this pathology. © 2023 Sociedad de Anestesiologia de Chile. All rights reserved.

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.

Role of Lung Ultrasonography (LUS) as a Tool for Evaluating Children with Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS).

BACKGROUND: Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a novel entity. The inflammatory process involves the circulatory, digestive, respiratory, and central nervous systems, as well as the skin. Making a diagnosis requires extensive differential diagnoses, including lung imaging. The aim of our study was to retrospectively assess the pathologies found in lung ultrasound (LUS) in children diagnosed with PIMS-TS and to evaluate the usefulness of the examination in diagnostics and monitoring. METHODS: The study group consisted of 43 children diagnosed with PIMS-TS, in whom LUS was performed at least three times, including on admission to hospital, on discharge, and 3 months after disease onset. RESULTS: Pneumonia (mild to severe) was diagnosed in 91% of the patients based on the ultrasound image; the same number had at least one pathology, including consolidations, atelectasis, pleural effusion, and interstitial or interstitial-alveolar syndrome. By the time of discharge, the inflammatory changes had completely regressed in 19% of the children and partially in 81%. After 3 months, no pathologies were detected in the entire study group. CONCLUSION: LUS is a useful tool for diagnosing and monitoring children with PIMS-TS. Inflammatory lesions of the lungs resolve completely when the generalized inflammatory process subsides.

Hemolytic anemia following intravenous immunoglobulins in children with PIMS-TS: Two case reports.

This is the first case report on two children presenting with immediate and severe hemolytic anemia following the administration of high-dose intravenous immunoglobulins (IVIGs) in the context of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Hemolytic anemia was described as a significant decrease in hemoglobin and an increase in lactate dehydrogenase after the second administration of high-dose IVIGs was performed. Both patients were found to have AB blood group. One of our patients showed massive pallor, weakness, and inability to walk in association with hemolysis. However, in both cases, the anemia was self-limiting and transfusion of red blood cells was not required: both patients recovered without persistent impact. Nonetheless, we aim to draw attention to this widely unknown adverse effect of IVIG, especially in the context of PIMS-TS. We suggest determining the patient's blood group prior to high-dose IVIG infusion and replacing the second IVIG through high-dose steroids or anticytokine therapy. Using IVIGs containing lower titers of specifically anti-A or anti-B antibodies to avoid isoagglutinin-caused hemolytic anemia is desirable; however, the information is not routinely available.

Polymorphism of clinical manifestations, experience of diagnosis and treatment of multisystem inflammatory syndrome associated with COVID-19 in children

Purpose - to analyze the literature data on possible variants of the course of pediatric multisystem inflammatory syndrome (PIMS-TS) in children;to describe our own experience in the diagnosis and treatment of some cases of PIMS-TS in children of different age groups;to present possible variants of clinical manifestations of the above disease;to draw attention to the need for early diagnosis and team care and treatment of such children. This novel clinical syndrome later identified as PIMS-TS temporally associated with SARS-CoV-2. In contrast with KD, PIMS-TS appears to occur in children at an older age with a predominance of gastrointestinal symptoms, hemodynamic instability, and myocardial dysfunction. However, the exact pathomechanism remains to be understood. Nevertheless, the post-viral immunological reaction is postulated to be the underlying mechanistic underpinnings. The paper describes the clinical course of the disease in a 5-year-old boy who complained of abdominal pain and hyperthermia, and the disease was masked by surgical pathology. The phenomena of intoxication syndrome, polyserositis, skin manifestations in the form of a polymorphic rash, hyperemia of the conjunctiva, swelling of the feet and hands increased in dynamics. The course of the disease in a 10-year-old girl who had symptoms of a viral infection is also described. However, upon going to the hospital, both children were diagnosed with a serious condition, they were hospitalized and given appropriate treatment. Therefore, the multifaceted nature of the PIMS-TS' course underlines the need for early recognition and multispecialty care and management. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. © 2022 Group of Companies Med Expert, LLC. All rights reserved.

GUIDELINES FOR IMMUNIZATION OF CHILDREN FOLLOWING MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN (MIS-C).

Multisystem inflammatory syndrome in children, MIS-C is also referred to as a paediatric inflammatory multisystem syndrome, PIMS. It is a late complication of SARS-CoV-2 infec-tion. The underlying cause is immunological dysregulation, leading to severe inflammatory processes. Children with PIMS require hospital treatment, the use of immunomodulating drugs, and often intensive care. The high effectiveness of COVID-19 vaccination has been demonstrated in the prevention of MIS-C in adolescents. However, there are no explic-it vaccination recommendations for children who have already suffered from MIS-C. We present a summary of current knowledge on vaccinations against COVID-19 in the context of MIS-C and the Polish guidance of vaccinations for children following MIS-C.Copyright © 2022, Wydawnictwo Czelej Sp. z o.o.. All rights reserved.

Oral lesions in paediatric patients with COVID-19 and Paediatric Inflammatory Multisystem Syndrome: a review

Paediatric patients comprise a small proportion of the SARS-CoV-2 infected population. They usually present with mild symptoms, however a small proportion of them may require intensive care due to shock and multi-organ failure related to Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS). This review article summarises the oral mucosal lesions in children with COVID-19 and PIMS-TS. The most common sites affected are the tongue and lips. Commonly reported lesions include cheilitis, dry and red lips, and tongue swelling. This article is of importance to all healthcare professionals involved in the multidisciplinary care for this group of patients.Copyright © 2021 The Authors

COVID-19 in children: what did we learn from the first wave?

A pandemic caused by the novel coronavirus, severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2), has caused high rates of mortality, predominantly in adults. Children are significantly less affected by SARS-CoV-2 with far lower rates of recorded infections in children compared to adults, milder symptoms in the majority of children and very low mortality rates. A suspected late manifestation of the disease, paediatric inflammatory multisystem syndrome - temporally associated with SARS-CoV-2 (PIMS-TS), has been seen in small numbers of children and has a more severe disease course than acute SARS-CoV-2. The pandemic has meant that children around the world have been kept off school, isolated from their extended family and friends and asked to stay inside. The UK has been declared as being in an economic recession and unemployment rates are increasing. These indirect effects of SARS-CoV-2 are likely to have a significant impact on many children for years to come. Consolidating the knowledge that has accumulated during the first wave of this pandemic is essential for recognising the clinical signs, symptoms and effective treatment strategies for children; identifying children who may be at increased risk of severe SARS-CoV-2 infection; planning the safe delivery of healthcare and non-health related services that are important for childrens' wellbeing; and engaging in, and developing, research to address the things that are not yet known. This article summarises the evidence that has emerged from the early phase of the pandemic and offers an overview for those looking after children or planning services.

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.

Characteristics and clinical outcomes of COVID-19 in children: a hospital-based surveillance study in Latin America's hardest-hit city.

Background: In 2020, Brazil became the epicentre of the coronavirus disease (COVID-19) pandemic in Latin America, resulting in an unparalleled health catastrophe. Nevertheless, comprehensive clinical reports in Brazilian children are not available. Methods: This retrospective, hospital-based, active surveillance study was performed to identify paediatric patients with COVID-19 who presented at a private academic medical centre in a large urban area between March 2020 and March 2021. Clinical and demographic information was analysed for those requiring hospitalization, those with severe illness and those with clinical syndromes. Results: In total, 964 symptomatic cases were evaluated; of these, 17.7% required hospitalization, and 27.5% of hospitalized cases were classified as severe/critical. Acute bronchiolitis and pneumonia were the most common causes of hospitalization among the severe cases. Twenty-seven hospitalized children fulfilled the diagnostic criteria for multi-system inflammatory syndrome (median age 29 months; 85.2% cases were non-severe). A significant co-existing condition was present in 29% of hospitalized children. The risk of hospitalization was higher in children with at least one comorbidity, children aged <2 years and obese children. Increased risk of severe disease was described among those with leukopenia, leukocytosis or any significant comorbidity. No deaths occurred among the study population. Conclusion: Although most children with COVID-19 experienced mild disease, and no deaths occurred among the study population, a significant proportion of cases required hospitalization and developed severe illness. Obesity, young age, underlying comorbidity, leukopenia and leukocytosis were risk factors for hospitalization or severe disease.

COVID-19-Associated Paediatric Inflammatory Multisystem Syndrome (PIMS-TS) in Intensive Care: A Retrospective Cohort Trial (PIMS-TS INT).

Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) is a new disease in children and adolescents that occurs after often asymptomatic or mild COVID-19. It can be manifested by different clinical symptomatology and varying severity of disease based on multisystemic inflammation. The aim of this retrospective cohort trial was to describe the initial clinical presentation, diagnostics, therapy and clinical outcome of paediatric patients with a diagnosis of PIMS-TS admitted to one of the 3 PICUs. All paediatric patients who were admitted to the hospital with a diagnosis of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) during the study period were enrolled in the study. A total of 180 patients were analysed. The most common symptoms upon admission were fever (81.6%, n = 147), rash (70.6%, n = 127), conjunctivitis (68.9%, n = 124) and abdominal pain (51.1%, n = 92). Acute respiratory failure occurred in 21.1% of patients (n = 38). Vasopressor support was used in 20.6% (n = 37) of cases. Overall, 96.7% of patients (n = 174) initially tested positive for SARS-CoV-2 IgG antibodies. Almost all patients received antibiotics during in-hospital stays. No patient died during the hospital stay or after 28 days of follow-up. Initial clinical presentation and organ system involvement of PIMS-TS including laboratory manifestations and treatment were identified in this trial. Early identification of PIMS-TS manifestation is essential for early treatment and proper management of patients.

Lower Risk of Multisystem Inflammatory Syndrome in Children (MIS-C) with the Delta and Omicron variants of SARS-CoV-2.

Little is known about the MIS-C risk with different SARS-CoV-2 variants. In Southeast England, MIS-C rates per confirmed SARS-CoV-2 infections in 0-16 years-olds were 56% lower (rate ratio, 0.34; 95%CI, 0.23-0.50) during pre-vaccine Delta, 66% lower (0.44; 0.28-0.69) during post-vaccine Delta and 95% lower (0.05; 0.02-0.10) during the Omicron period.

Epidemiological and clinical characteristics of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the Czech Republic

Objective: The aim of this study was to analyse epidemiology and clinical course of paediatric inflammatory multi-system syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the Czech Republic. Methods: We performed a retrospective-prospective nationwide observational study based on patients hospital-ised with PIMS-TS according to World Health Organization definition and who were admitted to a hospital in the Czech Republic between November 1st, 2020, and May 31st, 2021. The anonymised data of patients (demographic and clinical data) were obtained from their medical records. Some of the data from the above-mentioned study period were compared with the results of a smaller set of patients from the next pandemic wave. The second nationwide observation period followed from June 1st, 2021, to March 31st, 2022. This period was characterized by prevailing delta and subsequently omicron variants. Results: Between November 1st, 2020 and May 31st, 2021, the total number of diagnosed patients with PIMS-TS in the Czech Republic was 207. The overall incidence was 1:10,100 of the paediatric population aged 0–19 years;and 1:1,127 out of all children who tested positive for SARS-CoV-2, respectively. During follow-up, only two patients (1.2%) had persistent coronary artery dilation, all patients had normal cardiac function. Between June 1st, 2021 and March 31st, 2022, PIMS-TS was diagnosed in additional 222 children. Whereas PIMS-TS was frequent during the prevailing delta variant, the predominating omicron variant led to its decline to one fourth in relation to numbers of those tested positively for SARS-CoV-2. The total number of children affected by PIMS-TS reached 429, with no reported fatalities. Conclusion: Above expectation outcome with no death could be explained by awareness campaigns and national guidelines with early use of combined immunosuppressive treatment. © 2022, Czech Medical Association J.E. Purkyne. All rights reserved.