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.

Exclusion of Alternative Diagnoses in Children with Suspected Pimsts Referred to a Regional Critical Care Transport Service in the Uk: A Retrospective Audit

BACKGROUND AND AIM: Paediatric inflammatory multisystem syndrome temporally related with COVID-19 (PIMS-TS) has considerable overlap in presentation with Kawasaki disease, sepsis, toxic shock syndrome, and surgical abdominal pathology. National consensus guidelines were published in the United Kingdom in September 2020, detailing investigations that should be undertaken to exclude other diagnoses. This retrospective audit aimed to assess referrals to our regional critical care transport service to ascertain whether alternative diagnoses are being excluded in children with suspected PIMS-TS. METHOD(S): 66 referrals were made to the transport service from September 2020 to 2021 with a provisional diagnosis of COVID-19, PIMS-TS, atypical Kawasaki disease, acute abdomen or cardiac disease. Referral documentation was examined and excluded if PIMS-TS was not suspected, leaving a total of 41 referrals for audit. Documentation was examined for evidence of completion by the referring team of sepsis screen and abdominal imaging. RESULT(S): 24 (59%) patients had a sepsis screen already completed prior to referral. Of the remaining 17 referrals, 16 (94%) did not have a sepsis screen recommended by the transport service. 27 (66%) referrals had abdominal symptoms on referral. Of these, 9 (33%) had received abdominal imaging, 6 (22%) were recommended to receive imaging by the transport service, and 12 (44%) were not recommended to receive imaging. CONCLUSION(S): The majority of patients referred to the regional transport service had received a sepsis screen prior to referral. However the majority of patients with abdominal symptoms did not receive imaging. A referral proforma for suspected PIMS-TS patients has been developed to improve exclusion of alternative diagnoses.

Kawasaki Disease and COVID-19.

The recent passing away of Dr. Tomisaku Kawasaki, who first described what is now known as Kawasaki Disease (KD), and recent reports of a multisystem inflammatory disease in children associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (MIS-C), makes a review on KD and MIS-C timely. Kawasaki Disease is a systemic vasculitis with predilection for coronary arteries occurring mostly in early childhood. The main features are high fever, extensive skin rash, cheilitis with red, cracking, bleeding lips and strawberry tongue, conjunctivitis, erythema and induration of hands and feet, subsiding with periungual peeling, cervical lymphadenopathy, and coronary artery dilation/aneurysms. Treatment consists of intravenous (IV) immunoglobulin (Ig) plus acetylsalicylic acid. MIS-C is considered a cytokine storm with high fever, inflammation, multi-organ dysfunction, that shares features with KD, toxic shock, and macrophage activation syndrome. Many children require admission to paediatric intensive care units for circulatory support. Bacterial sepsis, staphylococcal toxic shock syndrome, and enterovirus-causing myocarditis should be excluded. Treatment is not standardized and includes IVIg, IV methylprednisolone and IL-6 and IL-1 inhibitors.

Responding to the psychological needs of children following admission to paediatric Intensive Care for paediatric inflammatory multisystem syndrome: A Narrative Therapy based Photography Workshop.

This article briefly describes the development of a novel narrative therapy-based photography workshop group for children following acute hospital admission for Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS). The workshop was a collaboration between the psychology team, an artist and the medical multi-disciplinary team (MDT) to develop a group during the COVID-19 pandemic. The aims were to reduce isolation and promote resilience and psychological recovery post discharge from hospital. Nine children aged 8-11 years joined the photography group. Parents (n = 8) and children (n = 8) provided feedback on the group through semi-structured telephone interviews. Thematic analysis of the interviews identified three narrative themes for parents: reducing isolation through shared experience, creative activity as a different experience of hospital, and the positive sharing of experiences after the day. The resulting narrative themes for the children included that the workshop was a fun and interactive day and an opportunity to share in hospital experience with peers.

Multisystem inflammatory syndrome in the context of paediatric COVID-19 infection in the Republic of Ireland April 2020 to April 2021.

AIM: Our aim was to describe the epidemiology of multisystem inflammatory syndrome in children (MIS-C) in the Republic of Ireland, in the context of all cases of COVID-19 in children, during the first year of the SARS-CoV-2 pandemic. METHODS: Cases of MIS-C were identified by prospective surveillance in Irish hospitals from April 2020 to April 2021. Paediatric COVID-19 cases and outbreaks in schools or childcare facilities were notified to and routinely investigated by Public Health. Univariate and bivariate analyses were carried out in Excel, Stata and JMP statistical package. RESULTS: Fifty-four MIS-C cases (median age 7.58 years; males 57%) were identified over the study period. MIS-C incidence was higher in certain ethnicities ('black' 21.3/100,000 [95% CI 4.3-38.4]; and 'Irish Traveller' 14.7/100,000 [95% CI -5.7-35.1]) than those of 'white' ethnicity (3.4 /100,000). MIS-C cases occurred in three temporal clusters, which followed three distinct waves of community COVID-19 infection, irrespective of school closures. Formal contact tracing identified an epidemiological link with a COVID-19-infected family member in the majority of MIS-C cases (77%). In contrast, investigation of COVID-19 school outbreaks demonstrated no epidemiological link with MIS-C cases during the study period. CONCLUSION: Efforts at controlling SARS-CoV-2 transmission in the community may be a more effective means to reduce MIS-C incidence than school closures. Establishing a mandatory reporting structure for MIS-C will help delineate the role of risk factors such as ethnicity and obesity and the effect of vaccination on MIS-C incidence.

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): a Brazilian cohort.

BACKGROUND: Paediatric inflammatory multisystem syndrome (PIMS) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been described since mid-April 2020 with the first reports coming from Europe. Our objective was to describe the characteristics of patients among the Brazilian population. METHODS: A multicenter retrospective study was conducted with the participation of five pediatric rheumatology centers in Brazil during the period from March to November 2020. Children and adolescents with PIMS temporally associated with SARS-CoV-2 (TS) who met the definition criteria for the disease according to the Royal College of Paediatrics and Child Health were included. Demographic, clinical, laboratory, therapeutic characteristics and molecular and serological diagnosis of SARS-CoV-2 infection were described. RESULTS: Fifty-seven children and adolescents with PIMS-TS were evaluated, 54% female, with a median age of 8 (3-11) years. Most (86%) were previously healthy, with asthma being the main comorbidity, present in 10% of the patients. Fever was the main manifestation, present in all patients, followed by mucocutaneous and gastrointestinal features, present in 89% and 81% of the patients, respectively. Myocarditis occurred in 21% of the patients and in 68% of them required intensive care. The Kawasaki disease phenotype occurred in most patients (77%). All patients had elevated inflammatory markers, with elevated CRP being the most found (98%). Anemia and lymphopenia were present in 79% and 72%, respectively. Laboratory evidence of SARS-CoV-2 was found in 77% of the patients, with 39% positive RT-PCR and 84% positive serology for SARS-CoV-2. An immunomodulatory treatment was performed in 91% of the patients, with 67% receiving intravenous immunoglobulin (IVIG) associated with glucocorticoid, 21% receiving IVIG, and 3.5% receiving glucocorticoid. The median length of hospitalization was 10 days. CONCLUSIONS: This study showed a high morbidity of PIMS-TS in Brazilian children, with a prolonged length of hospitalization and a high rate of admission to pediatric intensive care unit. Multicenter prospective studies are needed to assess the morbidity of the disease in the medium and long term.

Vitamin D status of children with paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS).

Coronavirus disease 2019 (COVID-19) has caused mild illness in children, until the emergence of the novel hyperinflammatory condition paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS). PIMS-TS is thought to be a post-SARS-CoV-2 immune dysregulation with excessive inflammatory cytokine release. We studied 25 hydroxyvitamin D (25OHD) concentrations in children with PIMS-TS, admitted to a tertiary paediatric hospital in the UK, due to its postulated role in cytokine regulation and immune response. Eighteen children (median (range) age 8·9 (0·3-14·6) years, male = 10) met the case definition. The majority were of Black, Asian and Minority Ethnic (BAME) origin (89 %, 16/18). Positive SARS-CoV-2 IgG antibodies were present in 94 % (17/18) and RNA by PCR in 6 % (1/18). Seventy-eight percentage of the cohort were vitamin D deficient (< 30 nmol/l). The mean 25OHD concentration was significantly lower when compared with the population mean from the 2015/16 National Diet and Nutrition Survey (children aged 4-10 years) (24 v. 54 nmol/l (95 % CI -38·6, -19·7); P < 0·001). The paediatric intensive care unit (PICU) group had lower mean 25OHD concentrations compared with the non-PICU group, but this was not statistically significant (19·5 v. 31·9 nmol/l; P = 0·11). The higher susceptibility of BAME children to PIMS-TS and also vitamin D deficiency merits contemplation. Whilst any link between vitamin D deficiency and the severity of COVID-19 and related conditions including PIMS-TS requires further evidence, public health measures to improve vitamin D status of the UK BAME population have been long overdue.

Paediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 [PIMS-TS] in a Patient Receiving Infliximab Therapy for Inflammatory Bowel Disease.

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 [PIMS-TS] is a newly described condition. It has a spectrum of presentations proposed to occur as part of a post-infectious immune response. We report the first case of PIMS-TS in a child on established anti-tumour necrosis factor alpha [anti-TNFα] therapy; a 10 year-old girl with ulcerative colitis treated with infliximab. The patient had 6 weeks of daily fever with mucocutaneous, gastrointestinal, renal, and haematological involvement. Biomarkers of hyperinflammation were present including: hyperferritinaemia [up to 691 µ/L; normal 15-80 µg/L], C-reactive protein [CRP] [ >100mg/L for  >10 days, normal 0-5 mg/L], erythrocyte sedimentation rate [ESR] consistently  >100mm/h [normal 0-15 mm/h], raised white cell count with neutrophilia, elevated D-dimer and lactate dehydrogenase [LDH], anaemia and Mott cells on bone marrow analysis. Extensive investigations for alternative diagnoses for pyrexia of unknown origin [PUO] were negative. The condition was refractory to treatment with intravenous immunoglobulin [IVIG] but improved within 24 h of high-dose methylprednisolone. Infliximab treatment followed and the patient has remained well at follow-up. Polymerase chain reaction [PCR] and serology for SARS-CoV-2 were negative. Current series report such negative findings in up to half of cases. The patient experienced a milder clinical phenotype without cardiac involvement, shock, or organ failure. Accepting the wide spectrum of PIMS-TS presentations, it is possible that previous anti-TNFα therapy may have attenuated the disease course. Given the uncertainty around therapeutic strategies for PIMS-TS, this case supports the need for further investigation into continuing infliximab as a treatment option for the condition.

A case of multisystem inflammatory syndrome in children in a Japanese boy: with discussion of cytokine profile.

The new disease concept of multisystem inflammatory syndrome in children (MIS-C), which is a systemic inflammatory syndrome with multiple organ involvement after SARS-CoV2 infection, was established in 2020. MIS-C is common in Hispanic and black children in Europe and North America, with few reports in East Asians. A significant portion of patients with MIS-C develop Kawasaki disease (KD)-like symptoms. Therefore, differential diagnosis is challenging, especially in East Asia, where KD is most prevalent. No Japanese cases have been reported in the literatures so far. We report a case of MIS-C in Japan with KD-like symptoms. A 9-year-old Japanese boy, who was infected with SARS-CoV2 1 month previously along with his family, was admitted to our hospital owing to fever for 6 d and erythema mainly in the groyne and pubic area. He also had conjunctivitis, strawberry tongue and diarrhoea. His laboratory findings were as follows: WBC, 12,840/µL (lymphocytes, 4%); CRP, 22.6 mg/dL, pro-calcitonin, 1.8 ng/mL (normal, <0.50 ng/mL); NT pro-BNP, 7627 pg/mL (<125 pg/mL); and troponin T, 0.14 ng/mL (<0.01 ng/mL). His cardiac function was normal. We initially diagnosed him with KD. His fever rapidly resolved with intravenous immunoglobulin (IVIG) and there were no coronary artery lesions. Desquamation of the fingers was observed later. Finally, a history of SARS-COV2 infection, his age, atypical skin rash, elevation of markers of inflammation and heart failure and lymphopenia suggested the diagnosis of MIS-C rather than KD. Differentiation between KD and MIS-C is necessary even in Japan, especially in patients with atypical features of KD.

Diagnosis and treatment of paediatric multisystem inflammatory syndrome / A gyermekkori koronavírus-fertozést követo sokszervi gyulladás diagnosztikája és kezelése.

Összefoglaló. A SARS-CoV-2-fertozés ritka gyermekkori szövodménye a sokszervi gyulladás, angol terminológiával paediatric inflammatory multisystem syndrome (PIMS). Két vagy több szerv érintettségével járó, súlyos tünetekkel induló betegségrol van szó, amelynek tünetei átfedést mutatnak a Kawasaki-betegséggel, a toxikus sokk szindrómával és a makrofágaktivációs szindrómával. A PIMS-betegek intenzív terápiás osztályon vagy intenzív terápiás háttérrel rendelkezo intézményben kezelendok, ahol biztosítottak a kardiológiai ellátás feltételei is. A szükséges immunterápia a klinikai prezentációtól függ. A jelen közleményben a szerzok a releváns nemzetközi irodalom áttekintését követoen ajánlást tesznek a PIMS diagnosztikai és terápiás algoritmusára. Orv Hetil. 2021; 162(17): 652-667. Summary. Pediatric inflammatory multisystem syndrome (PIMS) is a rare complication of SARS-CoV-2 infection in children. PIMS is a severe condition, involving two or more organ systems. The symptoms overlap with Kawasaki disease, toxic shock syndrome and macrophage activation syndrome. PIMS patients should be treated in an intensive care unit or in an institution with an intensive care background, where cardiological care is also provided. The required specific immunotherapy depends on the clinical presentation. In this paper, after reviewing the relevant international literature, the authors make a recommendation for the diagnostic and therapeutic algorithm for PIMS. Orv Hetil. 2021; 162(17): 652-667.

SARS-CoV-2-associated inflammatory multisystem disease in a 15-year-old boy / SARS-CoV-2-fertozéshez társuló többszervi megbetegedés 15 éves fiúban.

Összefoglaló. Újabb megfigyelések szerint a SARS-CoV-2-fertozést követoen gyermekekben a paediatric inflammatory multisystem syndrome (PIMS) elnevezésu, sokkállapottal szövodött Kawasaki-megbetegedéshez hasonlító, többszervi elégtelenségnek megfelelo tünetegyüttes alakulhat ki. A gyermekek többségében ilyenkor a direkt víruskimutatás már sikertelen, azonban a SARS-CoV-2 ellen képzodött antitest igazolhatja a diagnózist. Dolgozatunk célja az egyik elso hazai eset ismertetése. Egy 15 éves fiú került gyermek intenzív osztályos felvételre több napon át észlelt magas láz, kesztyu-, zokniszeru exanthema, conjunctivitis, többszervi elégtelenség, szeptikus sokk tüneteivel, akut gyulladásra utaló laboratóriumi eltérésekkel és diffúz hasi panaszokkal. Felvételét megelozoen néhány héttel SARS-CoV-2-fertozésen esett át. Felvételekor a direkt víruskimutatás sikertelen volt, ám a SARS-CoV-2 elleni antitest vizsgálata pozitív lett. Komplex intenzív terápia mellett állapota stabilizálódott. Az irodalmi ajánlásoknak megfeleloen immunglobulin-, acetilszalicilsav- és szteroidkezelésben részesítettük, melynek hatására állapota maradványtünetek nélkül rendezodött. A növekvo esetszámú gyermekkori SARS-CoV-2-fertozés mellett egyre gyakrabban várható a SARS-CoV-2-fertozést követo, a Kawasaki-betegség tüneteire emlékezteto PIMS kialakulása. Gyermekekben súlyos szeptikus állapot és többszervi elégtelenség esetén gondolni kell a PIMS lehetoségére, mely esetenként intenzív osztályos ellátást és célzott terápiát igényel. Legjobb tudomásunk szerint a leírásra került beteg a Magyarországon diagnosztizált egyik legkorábbi eset. Orv Hetil. 2021; 162(16): 602-607. Summary. Recently following SARS-CoV-2 infection, a new, multisystem disease (paediatric inflammatory multisystem syndrome, PIMS) with fever was recognized in children with shock and multiorgan failure. On of the first Hungarian cases will be described. A 15-year-old boy was admitted to the Paediatric Intensive Care Unit with persistent high fever, diffuse abdominal pain, septic shock, multiple organ failure, gloves- and socks-shaped cutan exanthema, conjunctivitis and laboratory signs of inflammation. Some weeks preceding his admission, symptoms of mild SARS-CoV-2 infection were revealed. At admission, the SARS-CoV-2 PCR and antigen tests were negative, however, the presence of IgG antibody was shown. Following complex supportive intensive care along with internationally recommended immunoglobulin, aspirin and steroid treatment, the patient was completely cured without any sequalae. In children after SARS-CoV-2 infection, PIMS could occur mimicking Kawasaki syndrome. At this time, in children virus PCR or antigen tests are usually negative already, but the presence of SARS-CoV-2 antibody could prove the preceding disease. Due to the increasing number of SARS-CoV-2 infections, the occurrence of post-SARS-CoV-2 PIMS in childhood is expected to increase. For paediatric patients, in case of severe septic state and multiple organ failure, PIMS should be also considered, which may require intensive care and targeted therapy. As far as we know, the described case is one of the earliest cases of PIMS in Hungary. Orv Hetil. 2021; 162(16): 602-607.

Family Transmission of COVID-19 Including a Child with MIS-C and Acute Pancreatitis.

INTRODUCTION: Spread of the novel coronavirus SARS-CoV-2, since at least December 2019, has caused a pandemic. SARS-CoV-2 causes the disease COVID-19, which can affect several human organs. Abdominal pain is one of the known symptoms, but little is known about acute pancreatitis as a complication. As well, knowledge about viral transmission in families is limited. This case report describes MIS-C and acalculous acute pancreatitis in a child who was a member of a family in which four of five members had COVID-19. CASE REPORT: A previously healthy family was infected by SARS-CoV-2 from an unknown source. The 13-year-old daughter was infected by SARS-CoV-2 and symptomatic during two periods, with an asymptomatic interval in-between. During the first period, she had transient and mild upper respiratory symptoms which was followed four weeks later by a secondary severe illness. At that point, there was inflammation in multiple organs and signs of Multisystem Inflammatory Syndrome in Children (MIS-C) and a Kawasaki-like disease with skin rash, scalded skin in hands and conjunctivitis. Myocarditis, bronchopneumonia, pancreatitis, and hepatopathy without encephalopathy were noted. She required assisted ventilation for 5 days. There were laboratory signs of disseminated intravascular coagulopathy. The multisystem inflammation was treated with intravenous immunoglobulin (IVIG) once a day for four days and immunotherapy (high dose methylprednisolone (IV) once a day, for 12 days, then tapered over 4 weeks, anakinra (IV) four times daily for 12 days), low molecular weight heparin for 22 days and salicylates for 6 weeks leading to full restoration of health. The two brothers and mother in the family had mild to moderate COVID-19 infections. The father was not affected despite close contact with his children. The household transmission and clinical course and outcome are described. No further known COVID-19 infection occurred in the neighborhood during or immediately after the family cluster was discovered. CONCLUSION: Penetrance and severity of COVID-19 can vary in family clusters. One adolescent showed a two-phase course with severe infection. This case report highlights MIS-C and acute pancreatitis as a complication associated with COVID-19 in children.

Management of severe hyperinflammation in the COVID-19 era: the role of the rheumatologist.

OBJECTIVES: The objectives of this study were (i) to describe the clinical presentation, treatment and outcome of paediatric inflammatory multisystem syndrome temporally related to Sars-CoV-2 (PIMS-TS) in children; (ii) to propose a framework to guide multidisciplinary team (MDT) management; and (iii) to highlight the role of the paediatric rheumatologist in this context. METHODS: This study involved a retrospective case notes review of patients referred to a single specialist paediatric centre with suspected PIMS-TS, with a focus on clinical presentation, laboratory parameters, treatment, and outcome in the context of an MDT framework. RESULTS: Nineteen children of median age 9.1 years fulfilled the definition of PIMS-TS and were managed within an MDT framework: 5/19 were female; 14/19 were of Black, Asian or minority ethnicity; 9/19 also fulfilled diagnostic criteria for complete or incomplete Kawasaki disease (KD). Severe systemic inflammation, shock, and abdominal pain were ubiquitous. Treatment was stratified within an MDT framework and included CSs in all; i.v. immunoglobulin in all; anakinra in 4/19; infliximab in 1/19; and antiviral (aciclovir) in 4/19. CONCLUSIONS: We observed significant diagnostic equipoise using a current definition of PIMS-TS, overlapping with KD. Outside of clinical trials, an MDT approach is vital. The role of the paediatric rheumatologist is to consider differential diagnoses of hyperinflammation in the young, to advise on empiric immunomodulatory therapy, to set realistic therapeutic targets, to gauge therapeutic success, to oversee timely step-down of immunomodulation, and to contribute to the longer-term MDT follow-up of any late inflammatory sequelae.