MIS-C Research Articles

Potential of Inflammatory Biomarkers as Diagnostic Tools for Paediatric Inflammatory Multisystemic Syndrome related to SARS-CoV-2: Literature Review

The World Health Organization has named the enveloped RNA virus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clinical aspects and pathogenic mechanisms between hyperinflammatory disease and SARS-CoV-2 are triggering factor for the out brake of autoinflammation disease and autoimmune dysregulation. This condition is known as Paediatric Inflammatory Multisystem Syndrome Temporally (PIMS-TS) related to SARS-CoV-2 or Multisystem Inflammatory Syndrome in Children (MIS-C) related to COVID-19. There are similarities between MIS-C and other diseases, that is overlapping clinical manifestations that lead to delaying diagnosis. Therefore, whether inflammatory biomarkers could be used to distinguish between these conditions are needed to be investigated. In orderd to distinguish MIS-C from infection and other inflammatory condition, it will continue to be a challenge as the COVID-19 pandemic. Therefore, a study is needed to investigate whether inflammatory biomarkers could be used to distinguish between these conditions.

SARS-CoV-2 Seroprevalence Study in Pediatric Patients and Health Care Workers Using Multiplex Antibody Immunoassays.

SARS-CoV-2 infection has become a global health problem specially exacerbated with the continuous appearance of new variants. Healthcare workers (HCW) have been one of the most affected sectors. Children have also been affected, and although infection generally presents as a mild disease, some have developed the Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We recruited 190 adults (HCW and cohabitants, April to June 2020) and 57 children (April 2020 to September 2021), of whom 12 developed PIMS-TS, in a hospital-based study in Spain. Using an in-house Luminex assay previously validated, antibody levels were measured against different spike and nucleocapsid SARS-CoV-2 proteins, including the receptor-binding domain (RBD) of the Alpha, Beta, Gamma, and Delta variants of concern (VoC). Seropositivity rates obtained from children and adults, respectively, were: 49.1% and 11% for IgG, 45.6% and 5.8% for IgA, and 35.1% and 7.3% for IgM. Higher antibody levels were detected in children who developed PIMS-TS compared to those who did not. Using the COVID-19 IgM/IgA ELISA (Vircell, S.L.) kit, widely implemented in Spanish hospitals, a high number of false positives and lower seroprevalences compared with the Luminex estimates were found, indicating a significantly lower specificity and sensitivity. Comparison of antibody levels against RBD-Wuhan versus RBD-VoCs indicated that the strongest positive correlations for all three isotypes were with RBD-Alpha, while the lowest correlations were with RBD-Delta for IgG, RBD-Gamma for IgM, and RBD-Beta for IgA. This study highlights the differences in antibody levels between groups with different demographic and clinical characteristics, as well as reporting the IgG, IgM, and IgA response to RBD VoC circulating at the study period.

Intussusception, A Rare Presentation of MIS-C

Intussusception refers to the invagination of one part of intestine into itself. It is the most common abdominal emergency encountered in children younger than 2 years of age. Multisystem inflammatory syndrome in children or pediatric inflammatory multisystem syndrome temporally associated with covid -19{PIMS-TS} is a relatively rare complication of COVID 19 infection occurring in<1% of children who may have a past history of confirmed covid-19 infection. Many cases of intussusception are reported when a child suffers from acute covid 19 infection. But a case of intussusception which itself is a manifestation of MIS-C is not reported so far. A 7-year-old boy presented with fever, abdomen pain was found to have ileocolic intussusception. It was then successfully reduced pneumatically. But he continued to have high temperatures and later developed mucocutaneous manifestations and shock. Keeping the current pandemic in view, he was investigated and was found to be suffering from MIS-C. He was then treated by our hospital protocol successfully. This is a rare presentation of MIS-C, and so is reported here. This 7year old boy presented with fever, abdomen pain and was found to have ileocolic intussusception. It was then reduced pneumatically. He continued to have high temperature and later developed mucocutaneous manifestations and shock. With the investigations, he was found to be suffering from MIS-C. He was then treated by our hospital MISC-C protocol successfully. This is a rare presentation of MIS-C, which warrants a high index of suspicion.

Initial protection against SARS-CoV-2 omicron lineage infection in children and adolescents by BNT162b2 in Israel: an observational study

BackgroundThe BNT162b2 (Pfizer-BioNTech) two-dose vaccine regiment for children and the BNT162b2 third dose for adolescents were approved shortly before the SARS-CoV-2 omicron (B.1.1.529) outbreak in Israel. We aimed to estimate the effects of these vaccines on the rates of confirmed infection against the omicron variant in children and adolescents.MethodsIn this observational cohort study, we extracted data for the omicron-dominated (sublineage BA.1) period. We compared rates of confirmed SARS-CoV-2 infection between children aged 5–10 years 14–35 days after receiving the second vaccine dose with an internal control group of children 3–7 days after receiving the first dose (when the vaccine is not yet effective). Similarly, we compared confirmed infection rates in adolescents aged 12–15 years 14–60 days after receiving a booster dose with an internal control group of adolescents 3–7 days after receiving the booster dose. We used Poisson regression, adjusting for age, sex, socioeconomic status, calendar week, and exposure.FindingsBetween Dec 26, 2021, and Jan 8, 2022, we included 1 158 289 participants. In children aged 5–10 years, the adjusted rate of confirmed infection was 2·3 times (95% CI 2·0–2·5) lower in children who received a second dose than in the internal control group. The adjusted infection rate in children who received a second dose was 102 infections per 100 000 risk-days (94–110) compared with 231 infections per 100 000 risk-days (215–248) in the corresponding internal control cohort. In adolescents aged 12–15 years, the booster dose decreased confirmed infection rates by 3·3 times (2·8–4·0) compared with in the internal control group. The adjusted infection rate of the booster cohort was 70 per 100 000 risk-days (60–81) compared with 232 per 100 000 risk-days (212–254) in the internal control cohort.InterpretationA recent two-dose vaccination regimen with BNT162b2 and a recent booster dose in adolescents substantially reduced the rate of confirmed infection compared with the internal control groups. Future studies are needed to assess the duration of this protection and protection against other outcomes such as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 and long-COVID.FundingNone.

Risk factors for admission to the pediatric critical care unit among children hospitalized with COVID-19 in France.

BackgroundCOVID-19 infection is less severe among children than among adults; however, some patients require hospitalization and even critical care. Using data from the French national medico-administrative database, we estimated the risk factors for critical care unit (CCU) admissions among pediatric COVID-19 hospitalizations, the number and characteristics of the cases during the successive waves from January 2020 to August 2021 and described death cases.MethodsWe included all children (age < 18) hospitalized with COVID-19 between January 1st, 2020, and August 31st, 2021. Follow-up was until September 30th, 2021 (discharge or death). Contiguous hospital stays were gathered in “care sequences.” Four epidemic waves were considered (cut off dates: August 11th 2020, January 1st 2021, and July 4th 2021). We excluded asymptomatic COVID-19 cases, post-COVID-19 diseases, and 1-day-long sequences (except death cases). Risk factors for CCU admission were assessed with a univariable and a multivariable logistic regression model in the entire sample and stratified by age, whether younger than 2.ResultsWe included 7,485 patients, of whom 1988 (26.6%) were admitted to the CCU. Risk factors for admission to the CCU were being younger than 7 days [OR: 3.71 95% CI (2.56–5.39)], being between 2 and 9 years old [1.19 (1.00–1.41)], pediatric multisystem inflammatory syndrome (PIMS) [7.17 (5.97–8.6)] and respiratory forms [1.26 (1.12–1.41)], and having at least one underlying condition [2.66 (2.36–3.01)]. Among hospitalized children younger than 2 years old, prematurity was a risk factor for CCU admission [1.89 (1.47–2.43)]. The CCU admission rate gradually decreased over the waves (from 31.0 to 17.8%). There were 32 (0.4%) deaths, of which the median age was 6 years (IQR: 177 days–15.5 years).ConclusionSome children need to be more particularly protected from a severe evolution: newborns younger than 7 days old, children aged from 2 to 13 years who are more at risk of PIMS forms and patients with at least one underlying medical condition.

MIS-C related to SARS-CoV-2 infection: a narrative review of presentation, differential diagnosis, and management.

Multisystem Inflammatory Syndrome in Children (MIS-C), a rare condition, has been reported approximately 2-4 weeks after the onset of COVID-19 in children and adolescents, causing inflammation in multiple systems, including cardiovascular and respiratory, digestive, and central nervous systems. This condition is also known as hyperinflammatory shock, Kawasaki-like disease, and Pediatric Inflammatory Multisystem Syndrome (PIMS). The signs and symptoms include but are not limited to fever, rash, peripheral edema, gastrointestinal symptoms, conjunctivitis, and shock. Thirty-eight studies met our criteria, with a total of 5822 patients. The most affected population was between 5-18 years of age. We noted that MIS-C presented with a wide range of signs and symptoms that overlap with Kawasaki Disease, including high fever, sore throat, malaise, tachypnea, tachycardia, conjunctival injection, mucosal edema, cardiac involvement, and gastrointestinal symptoms. It causes an increase in IL-17A, IL-6, and arterial damage, a distinct difference from Kawasaki disease. The laboratory findings in MIS-C showed an increase in inflammatory markers like CRP, ESR, ferritin, leukocytes, and TNF-α. WHO stated that 23% of affected children with MIS-C had underlying conditions like chronic lung diseases, cardiovascular disease, and immunosuppression. In most affected children, aspirin and IVIG were successful, which resulted in a decrease in the inflammatory markers. We find that MIS-C is a rare, but potentially fatal pediatric complication, after COVID-19 infection. The aim of this article is to study the emerging relationship between COVID-19 and MIS-C in children and adolescents affected by this condition, to discuss the immunological mechanisms, and explore potential therapies.

Clinical and laboratory characteristics of patients with paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS)

Abstract Introduction. Paediatric Inflammatory Multisystem Syndrome Temporally Associated with COVID-19 (PIMS-TS) is a rare complication of SARS-CoV-2 infection in children. There are also problems with the digestive system (vomiting, diarrhea, abdominal pain), conjunctivitis, headaches, swelling of the hands and feet, and others. Aim. The aim of the study is the clinical and laboratory evaluation of patients meeting the PIMS-TS criteria according to the RCPCH. This study aimed to determine the clinical and laboratory characteristics of patients meeting criteria for PIMS-TS. Material and methods. The study was a retrospective analysis of hospital records of 29 PIMS-TS patients of the Provincial Paediatric Hospital in Bydgoszcz hospitalised between November 2020 and August 2021. Results. Fever was found in 100% of the patients. Other symptoms re-ported were gastrointestinal problems, headache, apathy, oral inflammation, and more. Every fourth patient was diagnosed with pulmonary interstitial lesions in the form of smudgy or fine patchy thickening. Echocardiographic tests showed decreased left ventricular contractility in 10 patients. Reduced left ventricular fractional shortening below 28% was found in four patients and ejection fraction below 55% in five patients. In every second child, abdominal ultrasound imaging showed lesions such as enlarged mesenteric lymph nodes, peritoneal effusion, or enlarged liver. Changes were also confirmed by laboratory tests. Conclusions. Patients with PIMS-TS showed increased levels of inflammatory and myocardial dysfunction markers. The long-term prognosis for PIMS-TS is still uncertain. Further research and observation are needed to determine long-term complications and the actual pathomechanisms of the disease.

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

PurposeTo 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.MethodsIn 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.ResultsThe 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.ConclusionThe 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.

Clinical and Evolutionary Features of SARS-CoV-2 Infection (COVID-19) in Children, a Romanian Perspective.

Background: Given the potential for additional development to clarify a better knowledge of generally influence of COVID-19 upon the pediatric population, the clinical symptoms of SARS-CoV-2 infection in children and adolescents are still being explored. Morbidity in children is characterized by a variable clinical course. Our study’s goal was to compare clinical aspects of 230 pediatric patients who analyzed positive for SARS-CoV-2 and were hospitalized between April 2020 and March 2022. Methods: This retrospective study aimed to compare the clinical characteristics of coronavirus disease 2019, (COVID-19) in two groups of pediatric patients hospitalized in the infectious disease clinical ward IX at the National Institute for Infectious Diseases “Prof. Dr. Matei Bals,” Bucharest, Romania. Clinical characteristics of 88 patients (first group), admitted between April–December 2020 were compared with the second group of 142 children admitted between July 2021 and March 2022. Results: Of 230 children, the median age was 4.5 years, and 53.9% were male. Fever (82.17%) and sore throat (66%) were the most common initial symptoms. Rhinorrhea (42%), cough (34%) and diarrhea (41.74%), with abdominal pain (26%) were also reported in a considerable number of cases. 88 (36.21%) patients (first group) were admitted during the second wave in Romania, mostly aged <5 years old, and experienced digestive manifestations like fever (p = 0.001), and diarrhea (p = 0.004). The second group experienced different clinical signs when compared with the first group, with higher temperature and increased respiratory symptoms analogous to persons who suffer acute respiratory viral infections. The proportion in the second group increased by 23.48% from the first group, and the 0–4 age group for both groups had symptoms for a median interval of 5 days; age (0–4-years old) and length of stay were both proportionally inversely and required longer hospitalization (5 days), for the first group. During study time, the fully vaccinated children for 5–12 years old were 10%, and for 13–18 years old, 14.35% respective. We report two Pediatric Inflammatory Multisystem Syndrome (PIMS) in the second group, with favorable evolution under treatment. Comorbidities (obesity and oncological diseases) were reported in both groups and are risk factors for complications appearing (p < 0.001). All pediatric cases admitted to our clinic evolved favorably and no death was recorded. Conclusions: Clinical characteristics of pediatric patients with COVID-19 are age-related. In the first group, 85.29% of 0–4 years old children experienced digestive symptoms, whereas in the second group 83.78% underwent mild and moderate respiratory symptoms for the 5–12 age range. The potential effects of COVID-19 infection in children older than 5 years should encourage caregivers to vaccinate and improve the prognosis among pediatric patients at risk.

Nationwide observational study of paediatric inflammatory multisystem syndrome temporally associated withSARS-CoV-2 (PIMS-TS) inthe Czech Republic.

The worldwide outbreak of the novel 2019 coronavirus disease (COVID-19) has led to recognition of a new immunopathological condition: paediatric inflammatory multisystem syndrome (PIMS-TS). The Czech Republic (CZ) suffered from one of the highest incidences of individuals who tested positive during pandemic waves. The aim of this study was to analyse epidemiological, clinical, and laboratory characteristics of all cases of paediatric inflammatory multisystem syndrome (PIMS-TS) in the Czech Republic (CZ) and their predictors of severe course. We performed a retrospective-prospective nationwide observational study based on patients hospitalised with PIMS-TS in CZ between 1 November 2020 and 31 May 2021. The anonymised data of patients were abstracted from medical record review. Using the inclusion criteria according to World Health Organization definition, 207 patients with PIMS-TS were enrolled in this study. The incidence of PIMS-TS out of all SARS-CoV-2-positive children was 0.9:1,000. The estimated delay between the occurrence of PIMS-TS and the COVID-19 pandemic wave was 3 weeks. The significant initial predictors of myocardial dysfunction included mainly cardiovascular signs (hypotension, oedema, oliguria/anuria, and prolonged capillary refill). During follow-up, most patients (98.8%) had normal cardiac function, with no residual findings. No fatal cases were reported.Conclusions: A 3-week interval in combination with incidence of COVID-19 could help increase pre-test probability of PIMS-TS during pandemic waves in the suspected cases. Although the parameters of the models do not allow one to completely divide patients into high and low risk groups, knowing the most important predictors surely could help clinical management. What is Known: • Preliminary evidence, majority from relatively small, and mostly single-centre patient cohorts, has shown some insights in the basic epidemiological and clinical data of children with a paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). What is New: • To our knowledge, this is the unique published national population-wide cohort allowing to study the epidemiology (including overall incidence), time gap between viral exposure and clinical symptoms of PIMS-TS, and clinical presentations and outcomes within the individual pandemic waves of COVID-19 that were characterised by various prevailing genetic variants of SARS-CoV-2.• We estimated 3-week interval as a most probable period between SARS-CoV-2 infection and PIMS-TS based on nationwide population data using cross-correlation method.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00431-022-04593-7.

ПЕРВЫЙ ОПЫТ ПРИМЕНЕНИЯ ЭКСТРАКОРПОРАЛЬНОЙ МЕМБРАННОЙ ОКСИГЕНАЦИИ У ДЕВОЧКИ С ДЕТСКИМ МУЛЬТИСИСТЕМНЫМ ВОCПАЛИТЕЛЬНЫМ СИНДРОМОМ, АССОЦИИРОВАННЫМ С COVID-19

Pediatric inflammatory multisystem syndrome (PIMS) associated with the new coronavirus infection is the most severe late complication of the COVID-19 infection in children. We present the Russia’s first clinical observation of a 9 years old girl with PIMS with successful use of extracorporeal membrane oxygenation (ECMO) in treatment. The disease was characterized by rapid progression of myocardial dysfunction, shock, multiple organ failure, secondary hemophagocytic syndrome, and resistance to therapy. Intensive therapy, including glucocorticosteroids, tocilizumab, intravenous immunoglobulin, antiplatelet agents and anticoagulants, respiratory and cardiotonic support, ECMO, renal replacement therapy and antimicrobials have allowed the child to stabilize and recover.

Risk for severe outcomes of COVID-19 and PIMS-TS in children with SARS-CoV-2 infection in Germany

Although children and adolescents have a lower burden of SARS-CoV-2-associated disease compared to adults, assessing the risk for severe outcomes among SARS-CoV-2-infected children remains difficult due to a high rate of undetected cases. We combine data from three data sources — a national seroprevalence study (the SARS-CoV-2 KIDS study), the nationwide, state-based reporting system for PCR-confirmed SARS-CoV-2 infections in Germany, and a nationwide registry on children and adolescents hospitalized with either SARS-CoV-2 or pediatric inflammatory multisystem syndrome (PIMS-TS, also known as MIS-C) — in order to provide estimates on the risk of hospitalization for COVID-19-related treatment, intensive care admission, and death due to COVID-19 and PIMS-TS in children. The rate of hospitalization for COVID-19-related treatment among all SARS-CoV-2 seropositive children was 7.13 per 10,000, ICU admission 2.21 per 10,000, and case fatality was 0.09 per 10,000. In children without comorbidities, the corresponding rates for severe or fatal disease courses were substantially lower. The lowest risk for the need of COVID-19-specific treatment was observed in children aged 5–11 without comorbidities. In this group, the ICU admission rate was 0.37 per 10,000, and case fatality could not be calculated due to the absence of cases. The overall PIMS-TS rate was 2.47 per 10,000 SARS-CoV-2 infections, the majority being children without comorbidities.Conclusion: Overall, the SARS-CoV-2-associated burden of a severe disease course or death in children and adolescents is low. This seems particularly the case for 5–11-year-old children without comorbidities. By contrast, PIMS-TS plays a major role in the overall disease burden among all pediatric age groups.What is Known:• SARS-CoV-2-associated burden of disease in children is considered to be low, but accurate risk estimates accounting for clinically undiagnosed infections are lacking.• Asymptomatic SARS-CoV-2 infections are common in children.What is New:• We provide risk estimates for hospitalization for COVID-19-related treatment, ICU admission, death from COVID-19, and PIMS-TS for children with SARS-CoV-2 infections by pooling different data sources.• The risk for PIMS-TS exceeds the risk for severe COVID-19 in all age groups; the risk for severe COVID-19 is the lowest in 5–11 years old.

Multisystem inflammatory syndrome in children related to COVID-19: Data from a Mexican national referral children's hospital.

ObjectivesTo describe characteristics of patients with the pediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 (PIMS-TS)/multisystem inflammatory syndrome in children (MIS-C) and to identify factors associated with admission to the pediatric intensive care unit (PICU) in the Mexican children without coronavirus disease 2019 (COVID-19) vaccination.MethodsThis was a cross-sectional study performed at Hospital Infantil de Mexico Federico Gomez, a referral children's hospital in Mexico. The study included all cases that met the criteria for PIMS-TS/MIS-C, unvaccinated, between March 2020 and January 2022. The primary outcome was the admission to PICU. Associations of PICU admission with demographic and clinical variables were estimated using logistic regression analyses.ResultsWe identified a total of 90 cases, with a median age of 7.5 years old, 47 (52.2%) girls. A previously healthy status was recorded in 76 (85%) children. All patients had positive PCR, serology test, or COVID-19 exposure. PICU admission was reported in 41 (45.6%) children. No deaths were reported. Patients received as treatment only corticosteroids in 53.3% of the cases. In univariable analyses, baseline factors associated with PICU admission were older age, hypotension or shock, positive PCR test, hypoalbuminemia, elevated procalcitonin, ferritin, and lymphopenia. Age, shock at admission, and hypoalbuminemia remained independently associated in the multivariable analysis adjusted by gender and previously healthy status.ConclusionWe found a high proportion of previously healthy children in patients with PIMS-TS/MIS-C in our center. Critical care attention was received by nearly half of the children. The main treatment used was steroids. Age, shock at admission, and hypoalbuminemia were factors associated with PICU admission.

Risk factors of a severe course of pediatric multi-system inflammatory syndrome temporally associated with COVID-19

Pediatric multi-system inflammatory syndrome temporally associated with COVID-19 (PIMS-TS) is a serious complication of a previous SARS-CoV-2 infection. The disease causes multiple organ failure, but in some patients, a more severe course of the disease is observed. The treatment is multidirectional and depends on the severity and course of the disease, as some patients do not respond to the recommended treatment. The aim of this study was to identify laboratory risk factors affecting the more severe course of the disease and resistance to standard therapy. It is a single-center retrospective study considering 51 patients with PIMS-TS. Clinical features, laboratory results, and additional imaging tests data were taken into account. Fifty-one patients with PIMS-TS were hospitalized within a 16-month observation period. In the studied group, 26/51 children (51%) were girls. The mean age of patients was 7 years. Sex of the patient was not a risk factor for changes in cardiovascular system or severe course of the disease. Sixteen patients (31.3%) required transfer to the intensive care unit. Children with initially higher concentrations of NT-proBNP, troponin, creatinine, triglycerides, C-reactive protein, procalcitonin, ferritin, D-dimers and lower hematocrit, platelet count, lymphocytes, and ejection fraction should be strictly observed as they have a higher risk of severe course of the disease.Conclusions: Laboratory parameters especially markers of myocardial damage, markers of inflammation, blood count, as wells as biochemical parameters are significant risk indicators of severe course of PIMS -TS and their concentration can be defined as predictor of disease severity.What is Known:• Pediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS-TS) is a serious complication of a previous SARS-CoV-2 infection in the group of pediatric patients• Course of the disease may be severe, which may cause long-term complications and the need for longitudinal patient care.What is New:• Children with higher concentrations of NT-proBNP, troponin, creatinine, TG, CRP, PCT, ferritin, D-dimers and lower hematocrit, PLT, lymphocytes, and EF have a higher risk of a severe course of the disease.• Patients with high concentration of NT-proBNP, troponin, CRP, lactates, ferritin, D-dimers, creatinine and a lower concentration of PLT, albumin, leukocytes; lymphopenia, hyponatremia are at risk for intravenous immunoglobulin resistance.

WE8.6 Paediatric inflammatory multisystem syndrome presenting as acute appendicitis: a case report and literature review

AimsPaediatric inflammatory multisystem syndrome– temporally associated with SARS-CoV-2 (PIMS-TS) is a novel hyperinflammatory condition that most commonly presents with an acute abdomen. Here we present a case of PIMS-TS mimicking appendicitis and a review of the literature with a proposed protocol for managing abdominal pain in patients with recent SARS-CoV-2 infection.ResultsAn 8-year old girl presented with suspected appendicitis. She underwent a day case open appendicectomy with normal appendix confirmed on histology. Unfortunately, she re-presented the following day with persistently high fever and was investigated for post-appendicectomy complication. She was started on intravenous antibiotics. MRI of abdomen and pelvis showed no collection but evidence of lymphadenopathy. On post-operative day four she was transferred to the tertiary centre PICU for specialist management of suspected severe PIMS-TS.Common abdominal radiological findings in PIMS-TS include ascites, bowel wall thickening and mesenteric inflammation. In addition, CRP and ferritin have been found to be significantly higher in PIMS-TS. White cells may be raised with neutrophilia and lymphopaenia. In addition, highly deranged inflammatory markers in the context of a normal abdominal imaging are more consistent with PIMS-TS than appendicitis. We propose anyone with these findings is considered as having PIMS-TS and requires urgent imaging including combined senior surgical and paediatrician review.ConclusionPIMS-TS may present mimicking acute appendicitis and given the severe cardiac compromise that can develop in patients with PIMS-TS is it important to avoid unnecessary general anaesthetic and abdominal surgery where possible. Our proposed protocol could help reduce unnecessary abdominal surgery in these patients.

Case Series of Myocarditis Following mRNA COVID Vaccine Compared to Pediatric Multisystem Inflammatory Syndrome: Multicenter Retrospective Study.

Introduction: Since the development of COVID-19 vaccines, more than 4.8 billion people have been immunized worldwide. Soon after vaccinations were initiated, reports on cases of myocarditis following the second vaccine dose emerged. This study aimed to report our experience with adolescent and young adults who developed post-COVID-19 vaccine myocarditis and to compare these patients to a cohort of patients who acquired pediatric inflammatory multisystem syndrome (PIMS/PIMS-TS) post-COVID-19 infection. Methods: We collected reported cases of patients who developed myocarditis following COVID-19 vaccination (Pfizer mRNA BNT162b2) from all pediatric rheumatology centers in Israel and compared them to a cohort of patients with PIMS. Results: Nine patients with post-vaccination myocarditis were identified and compared to 78 patients diagnosed with PIMS. All patients with post-vaccination myocarditis were males who developed symptoms following their second dose of the vaccine. Patients with post-vaccination myocarditis had a shorter duration of stay in the hospital (mean 4.4 ± 1.9 vs. 8.7 ± 4.7 days) and less myocardial dysfunction (11.1% vs. 61.5%), and all had excellent outcomes as compared to the chronic changes among 9.2% of the patients with PIMS. Conclusion: The clinical course of vaccine-associated myocarditis appears favorable, with resolution of the symptoms in all the patients in our cohort.

Paediatric inflammatory multisystem syndrome in a neonate with CHD: case description and current issues in children with CHD.

We present a case of possible vertical COVID-19 transmission-related paediatric inflammatory multisystem syndrome in a neonate with CHD. Myocarditis and supraventricular tachycardia along with hepatic injury and renal failure were diagnosed on a background of mild aortic valve stenosis; the patient was successfully treated with immunomodulation. Since paediatric inflammatory multisystem syndrome can affect the heart, we could consider neonates with haemodynamically insignificant CHD to be at a higher risk of fatal outcomes. Issues related to early diagnosis and management need to be addressed.

Detection of Echovirus-18 in Children Suspected With SARS-CoV-2 Infection With Multisystem Inflammatory Syndrome: A Case Report From India

There have been several reports across the globe regarding the presentation of a severe multi-system hyperinflammatory syndrome, resembling Kawasaki disease (KD), in the pediatric population during the SARS-CoV-2 pandemic. The exact pathophysiology is still unclear; however, children typically demonstrate multi-organ dysfunction and less respiratory system involvement compared to adults. The limited literature is available at present for the identification and management of such patients. In this study, we investigated four cases in children ages 11–15 years that fulfilled the case definition for the pediatric multi-system inflammatory syndrome. All were found negative for SARS-CoV-2 from oropharyngeal swabs and stool. As they were having symptoms of diarrhea, tests for bacterial and enteric viral infections were performed after SARS-CoV-2 testing. Molecular analysis revealed that all the children were infected with enterovirus (Echovirus-18). Early and exact diagnosis is vital for timely, effective, and potentially life-saving management of such cases.

COVID-19 has exposed the need for health system assessments to be more child health-sensitive.

The COVID-19 pandemic is directly and indirectly impacting children’s health [1]. Although the evidence base in this area is expanding, there is still much we do not know. Paediatric Multisystem Inflammatory Syndrome temporally associated with COVID-19 (MIS-C: Multisystem Inflammatory Syndrome – Children) and long COVID are the most notable direct effects of COVID-19 infection on […]

Risk of pediatric inflammatory multi-system syndrome (PIMS or MIS-C) in pediatric patients with COVID-19 presenting with gastrointestinal symptoms.

Introduction and objectivesPediatric inflammatory multisystem syndrome (PIMS) is a life-threatening complication in pediatric patients with SARS-CoV-2 infection. An increase in the association of gastrointestinal symptoms and the presence of PIMS has been observed. The objective of this study was to analyze whether pediatric patients with COVID-19, who debut with gastrointestinal symptoms, have a higher risk of developing PIMS.Material and methodsAn observational, analytical and retrolective study was carried out with a review of the records of patients diagnosed with COVID-19. Demographic, clinical and laboratory variables were recorded.ResultsA total of 248 patients who met the selection criteria were included. Of Those 40% were female, with a mean age of 7 +/- 5.8 years. Gastrointestinal symptoms were the initial presentation in 103 patients, with vomiting being the most frequent symptom, followed by abdominal pain and diarrhea. In total 52 patients developed PIMS, 30 of whom presented with gastrointestinal symptoms. A RR of 1.57 (97% CI of 1.17–2.11) was found for the presentation of PIMS in patients positive for SARS-CoV-2 who present with gastrointestinal symptoms.ConclusionsThere is an increased risk of developing pediatric multisystem inflammatory syndrome when there are gastrointestinal symptoms in pediatric patients with COVID-19.