Multisystem inflammatory syndrome in children: clinical characteristics, diagnostic findings and therapeutic interventions at a tertiary care center in South of Italy

Introduction: Multisystem inflammatory syndrome in children (MISC), also known as paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS), is a condition characterised by persistent fever, elevation of inflammatory indexes and evidence of organs involvement or shock. Objectives: To describe clinical characteristics, diagnostic findings and therapeutic interventions of monocentric cohort of MIS-C. Methods: Diagnosis of MIS-C was done following CDC criteria. Patients were hospitalised at Santobono-Pausilipon Children's Hospital in Naples, Italy, from November 2020 to March 2021. Results: MIS-C was diagnosed in 29 patients, 14 males (48.3%). Mean age at diagnosis was 7,2 years old (range 4 months-12,9 years). Contact with SARS-CoV-2-positive patient emerged in 18/29 patients (62%) while 5/29 patients (17,2%) reported symptomatic COVID-19 in the weeks before. SARS-CoV-2 serologic assayrevealed IgG +/IgM- in 100% of the patients. No one presented concurrent conditions but obesity in 6/29 (20,7%). Mucocutaneous involvement was evidenced in 21/29 patients (72%), gastrointestinal symptoms 22/29 (75.9%), cardiac involvement in 27/29 (93,1%). The most frequent symptoms were fever (100%), conjunctivitis (65.5%), abdominal pain (62%), diarrhoea (48,2%), rash (44,9%), vomiting (31%) and cheilitis (31%). Laboratory findings are summarised in table 1. Troponin resulted elevated in 16/29 (55,1%), associated elevation of BNP was evidenced in 12/29 (62%). Electrocardiography showed alterations in 25/29 (86,2%) while echocardiography in 21/29 (72%). Concerning therapy, 27/29 (93%) patients underwent parenteral antibiotics at the admission. Intravenous immunoglobulin (IVIG) was performed in 25/29 (86,2%) of patients. Due to cardiac involvement 13/29 patients (44,8%) received bolus of steroids. 4/29 patients (13,8%) presented worsening of clinical and laboratoristic parameters during treatment with steroids, requiring Anakinra. One patient died due to cardiogenic shock at the admission. Conclusion: Mucocutaneous, gastrointestinal and cardiac involvement are the most common manifestations in our cohort, as also reported in literature. Biologic treatment was necessary in minority of patients. MIS-C is a new emerging condition and represent a challenge to paediatricians due to the severity of presentation. More data are needed to better define incidence and prognosis of that condition.

Early recognition of multisystem inflammatory syndrome temporally associated to COVID-19 in the emergency department: A single tertiary care centre experience

Introduction: Multisystem Inflammatory Syndrome in Children (MISC) is a new and life-threatening disease temporally associated to Covid-19. Objectives: The aim of the study is to analyze the clinical, laboratoristic and instrumental features of patients with diagnosis of MIS-C at the onset in order to early recognize the disease. Methods: We retrospectively reviewed clinical records of children admitted to our Emergency Department between April 2020 and March 2021, who were ultimately diagnosed with MIS-C associated with SARS-CoV2. Data collected included all clinical and laboratory parameters at presentation to the Emergency Department. We also recorded data regarding the duration of fever and hospitalization and the presence of abnormalities at chest X-ray, abdominal and cardiac ultrasound. Results: Clinical and laboratory data of the twenty-seven children retrospectively enrolled, including symptoms at presentation to the Emergency Department, are summarized in Table 1. Median duration of fever was 4 days (range 1.5 - 7). With the exception of fever, abdominal pain and diarrhea were the most frequent complaints at presentation. No significant differences were found between laboratory parameters in children with or without abdominal pain, diarrhea, vomit, conjunctivitis or rash. Heart ultrasound showed no abnormalities in 11 out of 27 children (41%). Findings in other children were mainly represented by mild pericardial effusion (29.6%) and mild mitral valve insufficiency (25.9%). Minor abnormalities in the interventricular septal dynamics were detected in 3 subjects (11.1%). Abdominal ultrasound was unremarkable in 5 out of 27 patients (18.5%). Most children (51.8%) had mild-to-moderate peritoneal effusion, which was often associated with ileal loops wall thickening (29.6%). The thickened segments were mostly located in proximity of the ileo-cecal valve or of the appendix. Mesenteric lymphadenitis was found in eleven children (40.7%). No significant differences were found in clinical or laboratory parameters between children with abnormal heart or abdominal ultrasounds and those without pathologic findings at these exams. Chest X ray at presentation showed no significant abnormalities in most patients, and only the child who died one day after admission showed bilateral basal opacities. Conclusion: The collected data allow to identify clinical and laboratoristic tic elements of patients admitted to Emergency care unit to provide early recognition of the MIS-C .The study included a modest sample size and for this reason the generalizability of results is limited. A national multicentre study is ongoing.

A child with a severe multi-system inflammatory syndrome following COVID-19 infection

Introduction: Despite the mild clinical course during the acute phase of COVID-19 infection in children, latest ongoing researches are pointing the attention towards a hyperinflammatory shock in pediatric patients as a possible consequence to COVID-19 exposure. Objectives: We report the case of a child with a severe systemic inflammatory syndrome following an asymptomatic COVID-19 infection. Methods: A 9-year-old male was admitted to the Pediatric Emergency Unit due to fever and abdominal pain. Symptoms started 7 days before admission, with fever, vomiting and non-bloodydiarrhea. Family history revealed that the father had been admitted to a COVID-19 Sub-Intensive Unit with bilateral interstitial pneumonia until 7 days before the onset of symptoms in the child. On the basis of familial history and because of the presence of fever, patient entered the COVID-19 pathway and was isolated. He had no chronic underlying disease nor history of previous hospitalization. At admission, he appeared stable. Body temperature was 38.1°C, O2 saturation was 98% in ambient area, blood pressure was 106/60 mm Hg, heart rate was 140 bpm, respiratory rate was 21 breaths per minute. On examination he was alert, there were no cough, runny nose or other respiratory symptoms. No conjunctivitis, rash or peripheral edema was detected. He had mild hepatomegaly. Results: The patient underwent blood and microbiological exams including blood specimens for cultures and nasopharyngeal swabs for SARS-COV2 nucleic acid (by RT-PCR-assay). At baseline, leukocytosis with neutrophilia and relative lymphopenia were found. Hemoglobin was below the normal range, while platelets count was normal. Inflammatory markers were strongly elevated, particularly CRP(420.8 mg/L), ferritin(4488 ng/mL), D-dimer(5106 ng/mL). Several significantly altered parameters suggested liver function abnormality, with hypertransaminasemia, acute renal injury, with elevated blood urea nitrogen and serum creatinine, and myocardial injury, with elevated high sensitivity cardiac troponin (434 ng/L) and brain natriuretic peptide (825 pg/mL). Lymphocyte subsets were within the normal range, while NK cells were slightly reduced. Patient was also tested for respiratory syncytial virus (RSV) and for influenza viruses A and B, resulted all negative. Bacteria and fungi blood cultures were sterile, as well as urine and stool cultures. He was tested for COVID-19 antibodies which showed positivity of both IgG and IgM (qualitative test), confirmed by a quantitative analysis which showed a high level of IgG (5066 AU/ml) and a weak positivity of IgM (0.532 AU/mL). Echocardiography showed no ventricular dysfunction, no dilatated coronaries or pericoronary iperechogenicity. Chest CT on the 2nd day showed two small bilateral areas of atelectasis associated to minimal pleural effusion more evident on the right side. The diagnosis of Hyperinflammatory syndrome COVID-19 related was made. Conclusion: Because of the high levels of BNP and troponin, IV methylprednisolone (5 mg/kg/day) and subcutaneous heparin (100 U/kg/day) were started after 24 hours since admission. Search for COVID-19 on nasopharyngeal swabs collected for 3 consecutive days resulted negative, The patient gradually recovered and fever disappeared after 48 hours. He presented no vomiting or diarrhea during the hospital stay, nor respiratory symptoms. Laboratory exams dramatically improved. According to his clinical and laboratoristic improvement, methylprednisolone was tapered to 3mg/kg/day and he started oral prednisone 1.25 mg/Kg/day four days after. He was discharged with steroid and heparin therapy and a close follow-up was planned.