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      Profile of Multisystem Inflammatory Syndrome in Children related to COVID-19: A Multicentric Study from South India

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          ABSTRACT

          Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection associated with significant morbidity and can be fatal if left unrecognized.

          A retrospective multicentric study was carried out at five tertiary care centers in South India, to evaluate the clinical profile of children admitted with MIS-C associated with SARS-CoV-2 infection. Cases of MIS-C diagnosed during October 2020 to December 2021 were included. Diagnosis of MIS-C was based on World Health Organization (WHO) criteria. All children underwent echocardiography at admission, discharge, and 4–6 weeks of follow-up. Children with MIS-C were treated with intravenous immunoglobulin (IVIG) and/or steroids. We compared younger children (<5 years of age) with older ones to determine if age at presentation could predict severity in children with MIS-C. A total of 81 children were diagnosed to have MIS-C during the study period. The mean age of presentation was 6.8 years. Around 29.6% of the children had a shock at admission and 54.3% had myocardial dysfunction. The average duration of a pediatric intensive care unit (PICU) stay was 6.6 days. Anti-SARS-CoV-2 antibodies were found to be positive in 75.3% of patients. Children with high N-terminal prohormone of brain natriuretic peptide (NT-proBNP) had more severe presentations. All children responded promptly to IVIG and steroids and the mortality was 0%. No difference was noted in terms of outcome between younger (<5 years) and older children. A significant proportion of children with MIS-C present with shock and myocardial dysfunction. Anti-SARS-CoV-2 antibodies were positive in 75% of children whose primary infection went unnoticed. We hereby report one of the largest cohorts of MIS-C patients from the Indian subcontinent.

          How to cite this article

          Bhattad S, Sadashiva R, Mohite RS, et al. Profile of Multisystem Inflammatory Syndrome in Children related to COVID-19: A Multicentric Study from South India. Pediatr Inf Dis 2023;5(2):37-41.

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          Hyperinflammatory shock in children during COVID-19 pandemic

          South Thames Retrieval Service in London, UK, provides paediatric intensive care support and retrieval to 2 million children in South East England. During a period of 10 days in mid-April, 2020, we noted an unprecedented cluster of eight children with hyperinflammatory shock, showing features similar to atypical Kawasaki disease, Kawasaki disease shock syndrome, 1 or toxic shock syndrome (typical number is one or two children per week). This case cluster formed the basis of a national alert. All children were previously fit and well. Six of the children were of Afro-Caribbean descent, and five of the children were boys. All children except one were well above the 75th centile for weight. Four children had known family exposure to coronavirus disease 2019 (COVID-19). Demographics, clinical findings, imaging findings, treatment, and outcome for this cluster of eight children are shown in the table . Table Demographics, clinical findings, imaging findings, treatment, and outcome from PICU Age; weight; BMI; comorbidities Clinical presentation Organ support Pharmacological treatment Imaging results Laboratory results Microbiology results PICU length of stay; outcome Initial PICU referral Patient 1 (male, AfroCaribbean) 14 years; 95 kg; BMI 33 kg/m2; no comorbidities 4 days >40°C; 3 days non-bloody diarrhoea; abdominal pain; headache BP 80/40 mmHg; HR 120 beats/min; RR 40 breaths per min; work of breathing; SatO2 99% NCO2 MV, RRT, VA-ECMO Dopamine, noradrenaline, argipressin, adrenaline milrinone, hydroxicortisone, IVIG, ceftriaxone, clindamycin RV dysfunction/elevate RVSP; ileitis, GB oedema and dilated biliary tree, ascites, bilateral basal lung consolidations and diffuse nodules Ferritin 4220 μg/L; D-dimers 13·4 mg/L; troponin 675 ng/L; proBNP >35 000; CRP 556 mg/L; procalcitonin>100 μg/L; albumin 20 g/L; platelets 123 × 109 SARS-CoV-2 positive (post mortem) 6 days; demise (right MCA and ACA ischaemic infarction) Patient 2 (male, AfroCaribbean) 8 years; 30 kg; BMI 18 kg/m2; no comorbidities 5 days >39°C; non-bloody diarrhoea; abdominal pain; conjunctivitis; rash BP 81/37 mmHg; HR 165 beats/min; RR 40 breaths/min; SVIA MV Noradrenaline, adrenaline, IVIG, infliximab, methylprednisolone, ceftriaxone, clindamycin Mild biventricular dysfunction, severely dilated coronaries; ascites, pleural effusions Ferritin 277 μg/L; D-dimers 4·8 mg/L; troponin 25 ng/L; CRP 295 mg/L; procalcitonin 8·4 μg/L; albumin 18 g/L; platelets 61 × 109 SARS-CoV-2 negative; likely COVID-19 exposure from mother 4 days; alive Patient 3 (male, Middle-Eastern) 4 years; 18 kg; BMI 17 kg/m2; no comorbidities 4 days >39°C; diarrhoea and vomiting; abdominal pain; rash; conjunctivitis BP 90/30 mmHg; HR 170 beats/min; RR 35 breaths/min; SVIA MV Noradrenaline, adrenaline, IVIG ceftriaxone, clindamycin Ascites, pleural effusions Ferritin 574 μg/L; D-dimers 11·7 mg/L; tropinin 45 ng/L; CRP 322 mg/L; procalcitonin 10·3 μg/L; albumin 22 g/L; platelets 103 × 109 Adenovirus positive; HERV positive 4 days; alive Patient 4 (female, AfroCaribbean) 13 years; 64 kg; BMI 33 kg/m2; no comorbidities 5 days >39°C; non-bloody diarrhoea; abdominal pain; conjunctivitis BP 77/41 mmHg; HR 127 beats/min; RR 24 breaths/min; SVIA HFNC Noradrenaline, milrinone, IVIG, ceftriaxone, clindamycin Moderate-severe LV dysfunction; ascites Ferritin 631 μg/L; D-dimers 3·4 mg/L; troponin 250 ng/L; proBNP 13427 ng/L; CRP 307 mg/L; procalcitonin 12·1 μg/L; albumin 21 g/L; platelets 146 × 109 SARS-CoV-2 negative 5 days; alive Patient 5 (male, Asian) 6 years; 22 kg; BMI 14 kg/m2; autism, ADHD 4 days >39°C; odynophagia; rash; conjunctivitis BP 85/43 mmHg; HR 150 beats/min; RR 50 breaths/min; SVIA NIV Milrinone, IVIG, methylprednisolone, aspirin, ceftriaxone Dilated LV, AVVR, pericoronary hyperechogenicity Ferritin 550 μg/L; D-dimers 11·1 mg/L; troponin 47 ng/L; NT-proBNP 7004 ng/L; CRP 183 mg/L; albumin 24 g/L; platelets 165 × 109 SARS-CoV-2 positive; likely COVID-19 exposure from father 4 days; alive Patient 6 (female, AfroCaribbean) 6 years; 26 kg; BMI 15 kg/m2; no comorbidities 5 days >39°C; myalgia; 3 days diarrhoea and vomiting; conjunctivitis BP 77/46 mmHg; HR 120 beats/min; RR 40 breaths/min; SVIA NIV Dopamine, noradrenaline, milrinone, IVIG, methylprednisolone, aspirin, ceftriaxone, clindamycin Mild LV systolic impairment Ferritin 1023 μg/L; D-dimers 9·9 mg/L; troponin 45 ng/L; NT-proBNP 9376 ng/L; CRP mg/L 169; procalcitonin 11·6 μg/L; albumin 25 g/L; platelets 158 SARS-CoV-2 negative; confirmed COVID-19 exposure from grandfather 3 days; alive Patient 7 (male, AfroCaribbean 12 years; 50kg; BMI 20 kg/m2; alopecia areata, hayfever 4 days >39°C; 2 days diarrhoea and vomiting; abdominal pain; rash; odynophagia; headache BP 80/48 mmHg; HR 125 beats/min; RR 47 breaths/min; SatO2 98%; HFNC FiO2 0.35 MV Noradrenaline, adrenaline, milrinone, IVIG, methylprednisolone, heparin, ceftriaxone, clindamycin, metronidazole Severe biventricular impairment; ileitis, ascites, pleural effusions Ferritin 958 μg/L; D-dimer 24·5 mg/L; troponin 813 ng/L; NT-proBNP >35 000 ng/L; CRP 251 mg/L; procalcitonin 71·5 μg/L; albumin 24 g/L; platelets 273 × 109 SARS-CoV-2 negative 4 days; alive Patient 8 (female, AfroCaribbean) 8 years; 50 kg; BMI 25 kg/m2; no comorbidities 4 days >39°C; odynophagia; 2 days diarrhoea and vomiting; abdominal pain BP 82/41 mmHg; HR 130 beats/min; RR 35 breaths/min; SatO2 97% NCO2 MV Dopamine, noradrenaline, milrinone, IVIG, aspirin, ceftriaxone, clindamycin Moderate LV dysfunction Ferritin 460 μg/L; D-dimers 4·3 mg/L; troponin 120 ng/L; CRP 347 mg/L; procalcitonin 7·42 μg/L; albumin 22 g/L; platelets 296 × 109 SARS-CoV-2 negative; likely COVID-19 exposure from parent 7 days; alive ACA= anterior cerebral artery. ADHD=attention deficit hyperactivity disorder. AVR=atrioventricular valve regurgitation. BMI=body mass index. BP=blood pressure. COVID-19=coronavirus disease 2019. CRP=C-reactive protein. FiO2=fraction of inspired oxygen. HERV=human endogenous retrovirus. HFNC=high-flow nasal canula. HR=heart rate. IVIG=human intravenous immunoglobulin. LV=left ventricle. MCA=middle cerebral artery. MV=mechanical ventilation via endotracheal tube. NIV=non-invasive ventilation. PICU=paediatric intensive care unit. RA=room air. RR=respiratory rate. RRT=renal replacement therapy. RV=right ventricle. RVSP=right ventricular systolic pressure. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. SatO2=oxygen saturation. SVIA=self-ventilating in air. VA-ECMO=veno-arterial extracorporeal membrane oxygenation. Clinical presentations were similar, with unrelenting fever (38–40°C), variable rash, conjunctivitis, peripheral oedema, and generalised extremity pain with significant gastrointestinal symptoms. All progressed to warm, vasoplegic shock, refractory to volume resuscitation and eventually requiring noradrenaline and milrinone for haemodynamic support. Most of the children had no significant respiratory involvement, although seven of the children required mechanical ventilation for cardiovascular stabilisation. Other notable features (besides persistent fever and rash) included development of small pleural, pericardial, and ascitic effusions, suggestive of a diffuse inflammatory process. All children tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on broncho-alveolar lavage or nasopharyngeal aspirates. Despite being critically unwell, with laboratory evidence of infection or inflammation 3 including elevated concentrations of C-reactive protein, procalcitonin, ferritin, triglycerides, and D-dimers, no pathological organism was identified in seven of the children. Adenovirus and enterovirus were isolated in one child. Baseline electrocardiograms were non-specific; however, a common echocardiographic finding was echo-bright coronary vessels (appendix), which progressed to giant coronary aneurysm in one patient within a week of discharge from paediatric intensive care (appendix). One child developed arrhythmia with refractory shock, requiring extracorporeal life support, and died from a large cerebrovascular infarct. The myocardial involvement 2 in this syndrome is evidenced by very elevated cardiac enzymes during the course of illness. All children were given intravenous immunoglobulin (2 g/kg) in the first 24 h, and antibiotic cover including ceftriaxone and clindamycin. Subsequently, six children have been given 50 mg/kg aspirin. All of the children were discharged from PICU after 4–6 days. Since discharge, two of the children have tested positive for SARS-CoV-2 (including the child who died, in whom SARS-CoV-2 was detected post mortem). All children are receiving ongoing surveillance for coronary abnormalities. We suggest that this clinical picture represents a new phenomenon affecting previously asymptomatic children with SARS-CoV-2 infection manifesting as a hyperinflammatory syndrome with multiorgan involvement similar to Kawasaki disease shock syndrome. The multifaceted nature of the disease course underlines the need for multispecialty input (intensive care, cardiology, infectious diseases, immunology, and rheumatology). The intention of this Correspondence is to bring this subset of children to the attention of the wider paediatric community and to optimise early recognition and management. As this Correspondence goes to press, 1 week after the initial submission, the Evelina London Children's Hospital paediatric intensive care unit has managed more than 20 children with similar clinical presentation, the first ten of whom tested positive for antibody (including the original eight children in the cohort described above).
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            Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association

            Kawasaki disease is an acute vasculitis of childhood that leads to coronary artery aneurysms in ≈25% of untreated cases. It has been reported worldwide and is the leading cause of acquired heart disease in children in developed countries.
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              Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2

              In communities with high rates of coronavirus disease 2019, reports have emerged of children with an unusual syndrome of fever and inflammation.
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                Author and article information

                Journal
                PID
                Pediatric Infectious Disease
                PID
                Jaypee Brothers Medical Publishers
                2582-4988
                April-June 2023
                : 5
                : 2
                : 37-41
                Affiliations
                [1-5,21 ]Department of Pediatrics, Aster CMI Hospital, Bengaluru, Karnataka, India
                [6-9 ]Department of Pediatrics, Aster Medcity Hospital, Kochi, Kerala, India
                [10-13 ]Department of Pediatrics, Aster MIMS Hospital, Calicut, Kerala, India
                [14-16 ]Department of Pediatrics, Aster RV Hospital, Bengaluru, Karnataka, India
                [17-20 ]Department of Pediatrics, Aster Women & Children Hospital, Bengaluru, Karnataka, India
                Author notes
                Sagar Bhattad, Department of Pediatrics, Aster CMI Hospital, Bengaluru, Karnataka, India, Phone: +91 9779433934, e-mail: drsagarbhattad@ 123456gmail.com
                Article
                10.5005/jp-journals-10081-1390
                58b55121-f303-4215-8a9d-bda5ffc4f925
                Copyright © 2023; The Author(s).

                © The Author(s). 2023 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 27 February 2023
                : 12 April 2023
                : 30 June 2023
                Categories
                ORIGINAL ARTICLE
                Custom metadata
                pid-05-037.pdf

                Pediatrics
                Multisystem inflammatory syndrome in children,Anti-severe complication of severe acute respiratory syndrome coronavirus 2 antibodies,Coronavirus disease 2019,Intravenous immunoglobulin,Myocardial dysfunction,Kawasaki disease

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