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Varadarajan P, Solomon RS, Subramani S, Subramanian R, Srividya G, Raghunathan E. Cardiovascular involvement in multisystem inflammatory syndrome in children and midterm follow-up from a pediatric tertiary center in India. World J Clin Pediatr 2025; 14:100453. [DOI: 10.5409/wjcp.v14.i1.100453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 10/02/2024] [Accepted: 10/30/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND In multisystem inflammatory syndrome in children (MIS-C) with coronavirus disease 2019, there was paucity of data from low-income and middle-income countries on cardiovascular involvement and its longitudinal outcomes. We planned to estimate the pattern of cardiovascular involvement among children with MIS-C and its mid-term outcomes.
AIM To determine association between cardiovascular abnormalities and clinical and laboratory parameters. To study the time-line for resolution of various abnormalities.
METHODS In this prospective study done in a tertiary care hospital, 270 were recruited from June 2020 to January 2022. Baseline demographic data and clinical presentation were recorded. Laboratory parameters and echocardiography were done at admission. Follow-up was done at 2 weeks, 3 months, 6 months and 1 year after diagnosis. Descriptive statistics were used for parametric and non-parametric data. Risk factors were identified by multivariate regression analysis.
RESULTS The 211 (78.2%) had cardiac involvement and 102 needed intensive care unit (ICU) admission. Cardiovascular abnormalities observed were shock 123 (45.6%), coronary dilatation 28 (10.4%), coronary aneurysm 77 (28.5%), left ventricular (LV) dysfunction 78 (29.3%), mitral regurgitation (MR) 77 (28.5%) and pericardial effusion 98 (36.3%). Coronary artery aneurysm/dilatation during follow-up at 2 weeks and 1 year were 25.7% and 0.9% respectively. Multivariate regression analysis revealed breathlessness [odds ratio (OR) = 3.91, 95%CI: 1.25-12.21, P = 0.019] and hi-flow nasal cannula (HFNC) support (OR = 8.5, 95%CI: 1.06-68.38, P = 0.044) as predictors of cardiovascular involvement. Higher mean age (OR = 1.16, 95%CI: 1.02-1.32, P = 0.026), breathlessness (OR = 4.99, 95%CI: 2.05-12.20, P < 0.001), gallop (OR = 4.45, 95%CI: 0.41-2.52, P = 0.016), MR (OR = 3.61, 95%CI: 1.53-8.53, P = 0.004) and invasive ventilation (OR = 4.01, 95%CI: 1.28-12.58, P = 0.017) were predictive of LV dysfunction. Altered sensorium (OR = 4.96, 95%CI: 2.23-11.02, P < 0.001), headache (OR = 6.61, 95%CI: 1.46-29.92, P = 0.014), HFNC (OR = 7.03, 95%CI: 2.04-24.29, P = 0.002), non-rebreathing mask usage (OR = 21.13, 95%CI: 9.00-49.61, P < 0.001) and invasive ventilation (OR = 5.64, 95%CI: 1.42-22.45, P = 0.014) were risk factors for shock. Anemia was a risk factor for coronary involvement (OR = 3.09, 95%CI: 1.79- 5.34, P < 0.001).
CONCLUSION Significant number of children with MIS-C had cardiovascular involvement contributing to higher ICU management. Although shock resolved quickly, resolution of ventricular function and coronary abnormalities were slower, and hence warrants a structured long-term follow-up protocol.
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Affiliation(s)
- Poovazhagi Varadarajan
- Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai 600003, Tamil Nādu, India
| | - Ritchie Sharon Solomon
- Department of Pediatric Cardiology, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai 600003, Tamil Nādu, India
| | - Seenivasan Subramani
- Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai 600003, Tamil Nādu, India
| | - Ramesh Subramanian
- Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai 600003, Tamil Nādu, India
| | - Gomathy Srividya
- Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai 600003, Tamil Nādu, India
| | - Elilarasi Raghunathan
- Department of Pediatrics, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai 600003, Tamil Nādu, India
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Padua-Zamora AP, Rey KLR, Tan-Lim CSC, Gregorio GEV. Gastrointestinal and Hepatic Manifestations of COVID-19 in Children: A Systematic Review and Meta-analysis. ACTA MEDICA PHILIPPINA 2024; 58:54-72. [PMID: 38882920 PMCID: PMC11168955 DOI: 10.47895/amp.v58i7.7054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/18/2024]
Abstract
Background Children with COVID-19 may present with gastrointestinal (GI) symptoms and liver dysfunction. Objective To determine the type and prevalence of gastrointestinal (GI) and hepatic manifestations of COVID-19 in children and its association with severity of illness. Methods A systematic literature search was done from inception until January 4, 2021 using PubMed, Cochrane Library, Google Scholar and prepublication repositories with no language restrictions. Studies that reported the demographic and clinical features of children with COVID-19 and provided data on their GI and hepatic signs and symptoms were included. Prevalence of GI and hepatic manifestations were pooled using Stata14. Results We included 58 studies with total of 4497 participants. Overall, one-third of children with COVID-19 presented with at least one GI symptom (33.8%; 95% confidence interval (CI) 23.0, 45.4; I2 97.5%; 42 studies, 3327 participants) with abdominal pain, nausea or vomiting, and diarrhea each occurring in approximately 20%. Children with severe COVID-19 were more likely to present with GI symptoms (odds ratio 2.59; 95% CI 1.35, 4.99; I2 24%; 4 studies, 773 participants). The pooled prevalence of elevated transaminases was 11% for both AST (11.3%, 95% CI 4.9, 19.3; I2 74.7%; 11 studies, 447 participants) and ALT (11.2%, 95% CI 7.1, 16.0; I2 40.8%; 15 studies, 513 participants). Hepatic findings such as jaundice (2-17%), hepatomegaly (2%) or behavioral changes (2%) from hepatic encephalopathy were variably reported by a few studies.The degree of heterogeneity was not improved on exclusion of studies with poor quality, but markedly improved on subgroup analysis according to geographical region and presence of MIS-C. Studies from China showed that children with COVID-19 had significantly lower pooled prevalence for any of the GI symptoms with low degree of heterogeneity, particularly for diarrhea, nausea/vomiting, and abdominal pain, all of which had I2 of 0%. Those with multisystem inflammatory syndrome in children (MIS-C) had significantly more common GI symptoms and increased transaminases than those without. Conclusion One-third of children with COVID-19 exhibit at least one GI symptom and more likely present in those with severe disease. Elevated transaminases were present in 10%. Prevalence of GI and hepatic manifestations were higher among children with MIS-C.
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Affiliation(s)
- April P Padua-Zamora
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Philippine General Hospital, University of the Philippines Manila
| | - Katrina Loren R Rey
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Philippine General Hospital, University of the Philippines Manila
| | - Carol Stephanie C Tan-Lim
- Division of Allergy and Immunology, Department of Pediatrics, Philippine General Hospital, University of the Philippines Manila
| | - Germana Emerita V Gregorio
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Philippine General Hospital, University of the Philippines Manila
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Şener S, Batu ED, Kaya Akca Ü, Atalay E, Kasap Cüceoğlu M, Balık Z, Başaran Ö, Karagöz T, Özsürekçi Y, Bilginer Y, Özen S. Differentiating Multisystem Inflammatory Syndrome in Children from Kawasaki Disease During the Pandemic. Turk Arch Pediatr 2024; 59:150-156. [PMID: 38454223 PMCID: PMC11059258 DOI: 10.5152/turkarchpediatr.2024.23192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 11/27/2023] [Indexed: 03/09/2024]
Abstract
OBJECTIVE We aimed to delineate the distinctive characteristics that aid in distinguishing between Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) with KD-like manifestations during the pandemic. MATERIALS AND METHODS We evaluated KD patients and MIS-C patients with KD-like symptoms admitted during the pandemic (between January 2021 and December 2022). RESULTS Thirty-three MIS-C patients and 15 KD patients were included. Kawasaki disease patients were younger than MIS-C patients (3.4 vs. 7.6 years). Rash (P = .044, 100% vs. 75.7%), oral mucosal changes (P = .044, 100% vs. 75.7%), and cervical lymphadenopathy (P = .001, 93.3% vs. 42.4%) were more common in KD. Multisystem inflammatory syndrome in children: patients had more hypotension (P = .002, 45.4% vs. 0), gastrointestinal (P .001, 72.7% vs. 13.3%), and respiratory symptoms (P = .044, 24.2% vs. 0). Multisystem inflammatory syndrome in children patients also had low lymphocyte and thrombocyte counts and elevated levels of d-dimer, ferritin, and cardiac parameters, unlike KD patients. Multisystem inflammatory syndrome in children patients exhibited a notable reduction in left ventricular systolic function in echocardiography. Another significant difference with regard to management was the anakinra treatment, which was prescribed for MIS-C patients. CONCLUSION Although MIS-C patients might display a clinical resemblance to KD, several features could help differentiate between MIS-C and classical KD. Specific clinical (hypotension, gastrointestinal, and respiratory symptoms) and laboratory (low lymphocyte and thrombocyte counts with higher C-reactive protein, ferritin, d-dimer, and cardiac parameters) features are characteristic of MIS-C. In addition, divergence in management strategies is evident between the 2 diseases, as biologic drugs were more prevalently employed in MIS-C patients than in classical KD patients.
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Affiliation(s)
- Seher Şener
- Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Ezgi Deniz Batu
- Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Ümmüşen Kaya Akca
- Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Erdal Atalay
- Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Müşerref Kasap Cüceoğlu
- Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Zeynep Balık
- Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Özge Başaran
- Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Tevfik Karagöz
- Division of Pediatric Cardiology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Yasemin Özsürekçi
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Yelda Bilginer
- Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Seza Özen
- Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
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Sarı E, Erdede Ö. Comparison of Eosinophil Counts in Inflammatory Conditions: Multisystem Inflammatory Syndrome in Children, Kawasaki Disease, and Infectious Mononucleosis. CHILDREN (BASEL, SWITZERLAND) 2024; 11:204. [PMID: 38397316 PMCID: PMC10887273 DOI: 10.3390/children11020204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 01/31/2024] [Accepted: 01/31/2024] [Indexed: 02/25/2024]
Abstract
This study examined the distinctions between multisystem inflammatory syndrome associated with coronavirus disease 2019, Kawasaki disease, and infectious mononucleosis. These three inflammatory disorders have commonalities according to clinical and laboratory results, particularly in relation to eosinophil levels. In this retrospective, single-center study, we documented the examination records (acute phase reactants and complete blood count) and clinical and cardiological findings of 130 patients diagnosed with multisystem inflammatory syndrome, Kawasaki disease, and infectious mononucleosis. These patients were treated and received follow-up care in our hospital from March 12, 2020, to September 13, 2022, as per the hospital records. Statistical analyses were performed using NCSS 2007, version 1 software. Eosinopenia was more prevalent in children with multisystem inflammatory syndrome than in those with Kawasaki disease, who showed normal or elevated eosinophil counts. The eosinophil counts in patients with infectious mononucleosis typically fell within the normal range. Our study found no correlation between the eosinophil counts and cardiac involvement in pediatric patients with either condition. These findings indicate a higher prevalence of eosinopenia in patients with multisystem inflammatory syndrome, irrespective of cardiac involvement, than in those with Kawasaki disease. Despite similarities in clinical findings, Kawasaki disease and multisystem inflammatory syndrome in children necessitate further studies for distinct characteristic elucidation.
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Affiliation(s)
- Erdal Sarı
- Department of Pediatrics, Zeynep Kamil Maternity and Children’s Disease Training and Research Hospital, University of Health Sciences, Istanbul 34668, Turkey;
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Abdeladim B, Massilia B, Aziza E, Zohair E, Ayad G, Maria R. Multisystem Inflammatory Syndrome in Children (MIS-C) in a Low-income Country: What Treatment Should be Adopted in Case of a Lack of Immunoglobulin? Rev Recent Clin Trials 2024; 19:150-157. [PMID: 38151848 DOI: 10.2174/0115748871257131231204114803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 09/27/2023] [Accepted: 10/10/2023] [Indexed: 12/29/2023]
Abstract
INTRODUCTION In multisystem inflammatory syndrome (MIS-C), children typically present high-grade fever, gastrointestinal symptoms, Kawasaki-like symptoms, and even a toxic shock-like syndrome days to weeks after recovering from SARS-CoV-2 infection. It is important to raise awareness of this condition in order to have early diagnosis and immediate treatment of patients. We have, herein, reported 44 cases of MIS-C with various risk factors and symptoms. Furthermore, we have emphasized the efficacy of experience in treating children with MIS-C with high-dose corticosteroids as an alternative to immunoglobulin in low-income countries. METHODS We conducted a targeted survey of MIS-C from early May 2020 to October 2022 on 44 children and adolescents with characteristics of multisystem inflammatory syndrome admitted to the pediatric department of the university hospital center in Oujda, Morocco, to which patients diagnosed with MIS-C were referred. The case definition included six criteria: serious illness leading to hospitalization, age under 18 years, fever of at least 24 hours, laboratory evidence of inflammation, multi-organ involvement, biological inflammatory syndrome, and evidence of coronavirus infection based on polymerase chain reaction, antibody testing or exposure to people with COVID-19 in the past month. The criteria used to diagnose myocarditis were impaired left ventricular function, central mitral leak, and elevation of BNP or pro-BNP. Coronary involvement was assessed by the z-score and the criteria for its presence was a z-score equal to or greater than 2.5. RESULTS Our study included 44 children and adolescents with MIS-C in our hospital, with male predominance (79%) and a median age of six years. Cardiovascular involvement was present in 91%, mucocutaneous in 78%, gastrointestinal in 70%, hematologic in 84%, and respiratory in 2% of patients. Coronary abnormalities (z-score ≥ 2.5) were documented in 21 cases (48%). Glucocorticoids were frequently used in comparison to immunoglobulin, which were uncommonly available and expensive. CONCLUSION The therapeutic protocol that was adopted was high doses of short-term prednisone (Cortancyl) at 4mg/kg/day for 4 days. Favorable outcome was noted in all patients over a 2-year period.
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Affiliation(s)
| | - Bouhmidi Massilia
- Department of Pediatrics, University Hospital Center Mohamed VI OUJDA, Morocco
| | - Elouali Aziza
- Department of Pediatrics, University Hospital Center Mohamed VI OUJDA, Morocco
| | - Elhaddar Zohair
- Department of Pediatrics, University Hospital Center Mohamed VI OUJDA, Morocco
| | - Ghanam Ayad
- Department of Pediatrics, University Hospital Center Mohamed VI OUJDA, Morocco
| | - Rkain Maria
- Department of Pediatrics, University Hospital Center Mohamed VI OUJDA, Morocco
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Shafaei B, Nafei Z, Karimi M, Behniafard N, Shamsi F, Faisal M, Amel Shahbaz AP, Akbarian E. Which Groups of Children Are at More Risk of Fatality during COVID-19 Pandemic? A Case-Control Study in Yazd, Iran. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2023; 2023:8838056. [PMID: 38130842 PMCID: PMC10735732 DOI: 10.1155/2023/8838056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 10/02/2023] [Accepted: 12/02/2023] [Indexed: 12/23/2023]
Abstract
Introduction The study aims to investigate the characteristics, comorbidities, laboratory findings, and clinical manifestations of under 18-year-old patients who died with the diagnosis of COVID-19 and determination of the most prevalent risk factors. Method This case-control study was performed at a referral hospital in Yazd from March 2020 to August 2021. All patients under 18 years who were diagnosed through real-time RT-PCR, chest computed tomography, and the World Health Organization definition were divided into deceased and survived groups. The characteristics (age and sex), disease severity, comorbidities, laboratory findings, and clinical manifestations of the two groups were compared and analyzed using SPSS, version 18 (SPSS Inc., Chicago, III., USA). Results A total of 24 patients in the deceased group and 167 patients in the survived group were compared. The highest mortality rate was observed in the age group of 1 month to 5 years, although no statistically significant relationship was found between age groups and the risk of mortality. Disease severity, dyspnea, low oxygen saturation on admission, length of hospital stays, and hospitalization history before the last admission were significantly correlated with mortality (P < 0.05). Lymphopenia increased the probability of mortality by more than two times (OR: 2.568; 95% CI (0.962-6.852)), but this was not the case for D-dimer and C-reactive protein. Furthermore, 27.5% of survived patients had normal chest CT scans, which was a statistically significant difference compared to the deceased patients (P: 0.031). Conclusion Based on the findings of this study, dyspnea, low oxygen saturation, and lymphopenia are critical indicators for identifying high-risk children with COVID-19 and triaging them for better care and treatment.
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Affiliation(s)
- Behnam Shafaei
- Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Zahra Nafei
- Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mehran Karimi
- Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Nasrin Behniafard
- Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Farimah Shamsi
- Center of Healthcare Data Modeling, Department of Biostatics and Epidemiology, School of Public Health, Shahid Sadoughi University of Sciences, Yazd, Iran
| | - Masoud Faisal
- Department of Radiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Amir Pasha Amel Shahbaz
- Department of Radiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Elahe Akbarian
- Children Growth Disorder Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Carmona CA, Kuziez M, Freitas CF, Cyrus JW, Bain J, Karam O. Cardiac manifestations of multisystem inflammatory syndrome of children after SARS-CoV-2 infection: a systematic review and meta-analysis. Cardiol Young 2023; 33:2319-2327. [PMID: 36762563 DOI: 10.1017/s104795112300015x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
This systematic review and meta-analysis were conducted to evaluate the prevalence of cardiac manifestations associated with multisystem inflammatory syndrome in children worldwide. We conducted electronic searches in Ovid MEDLINE, Ovid EMBASE, and the World Health Organization COVID-19 Literature Database from the inception of the SARS-CoV-2 pandemic to 1 January, 2022. Three authors independently screened the abstracts to determine eligibility, assessed methodology in the full texts, and extracted the data.We identified 2848 citations; 94 studies (14,932 patients) were included. The prevalence of vasopressors was 48.2% (95% CI 45.1%, 51.3%), left ventricular systolic dysfunction occurred in 37.2% (95% CI 34.1%, 40.3%), myocarditis in 34.1% (95% CI 30.5%, 37.8%), electrocardiographic dysrhythmias and abnormalities detected in 23.1% (95% CI 18.8%, 27.6%), coronary abnormalities identified in 18% (95% CI 16%, 20%), extracorporeal membrane oxygenation deployed in 2.2% (95% CI 1.7%, 2.8%), and mortality rate of 2.2% (95% CI 1.7%, 2.7%). A sensitivity analysis was performed after removing eleven studies with high bias, and the adjusted prevalence was not different than the original evaluation.In this meta-analysis of the largest cohort of multisystem inflammatory syndrome in children patients to date, we established the most accurate prevalence of the most common cardiac manifestations. Providers will subsequently have more precise data to anticipate patient outcomes and approach discussions concerning the frequency of monitoring outside the acute hospital period.
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Affiliation(s)
- Carlos A Carmona
- Division of Pediatric Critical Care Medicine, Children's Hospital of Richmond at VCU, Richmond, VA, USA
| | - Mohamed Kuziez
- Division of Pediatric Cardiology, Children's Hospital of Richmond at VCU, Richmond, VA, USA
| | - Caio F Freitas
- Division of Pediatrics, Advent Health for Children, Pediatrics Residency, Orlando, FL, USA
| | - John W Cyrus
- Tompkins-McCaw Library for the Health Sciences, VCU Libraries, Virginia Commonwealth University, Richmond, VA, USA
| | - Jesse Bain
- Division of Pediatric Critical Care Medicine, Children's Hospital of Richmond at VCU, Richmond, VA, USA
| | - Oliver Karam
- Division of Pediatric Critical Care Medicine, Children's Hospital of Richmond at VCU, Richmond, VA, USA
- Section of Pediatric Critical Care Medicine, Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA
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Kumar NP, Venkataraman A, Nancy A, Selvaraj N, Moideen K, Ahamed SF, Renji RM, Sasidaran K, Kumar S, Periyakuppan M, Sangaralingam T, Varadarajan P, Chelladurai E, Babu S. Immune Profiles in Multisystem Inflammatory Syndrome in Children with Cardiovascular Abnormalities. Viruses 2023; 15:2162. [PMID: 38005840 PMCID: PMC10674423 DOI: 10.3390/v15112162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/12/2023] [Accepted: 09/27/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND Multisystem inflammatory syndrome in children (MIS-C), a sequela of severe acute respiratory syndrome coronavirus-2 infection (SARS-CoV2), has been progressively reported worldwide, with cardiac involvement being a frequent presentation. Although the clinical and immunological characteristics of MIS-C with and without cardiac involvement have been described, the immunological differences between cardiac and non-cardiac MIS-C are not well understood. METHODS The levels of type 1, type 2, type 17, other proinflammatory cytokines and CC chemokines and CXC chemokines were measured using the Magpix multiplex cytokine assay system in MIS-C children with MIS-C cardiac (MIS-C (C) (n = 88)) and MIS-C non-cardiac (MIS-C (NC) (n = 64)) abnormalities. RESULTS MIS-C children with cardiac manifestations presented with significantly increased levels of cytokines such as IFN-γ, IL-2, TNFα, IL-5, IL-1α, IL-1β, IL-6, IL-10 and IL-12p70 and chemokines such as CCL2, CCL3, CCL11 and CXCL10 in comparison to MIS-C children without cardiac manifestations. Clustering analysis revealed that cytokines and chemokines could clearly distinguish MIS-C children with and without cardiac manifestations. In addition, these responses significantly diminished and normalized 9 months after treatment. CONCLUSIONS This is one of the first studies characterizing and differentiating systemic inflammation in MIS-C with and without cardiac involvement from a low- and middle-income country (LMIC). Our study contributes to the existing body of evidence and advances our knowledge of the immunopathogenesis of MIS-C in children.
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Affiliation(s)
- Nathella Pavan Kumar
- ICMR—National Institute for Research in Tuberculosis, Chennai 600031, India; (A.V.); (S.F.A.)
| | - Aishwarya Venkataraman
- ICMR—National Institute for Research in Tuberculosis, Chennai 600031, India; (A.V.); (S.F.A.)
| | - Arul Nancy
- National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai 600031, India; (A.N.); (N.S.); (K.M.); (R.M.R.); (S.B.)
| | - Nandhini Selvaraj
- National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai 600031, India; (A.N.); (N.S.); (K.M.); (R.M.R.); (S.B.)
| | - Kadar Moideen
- National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai 600031, India; (A.N.); (N.S.); (K.M.); (R.M.R.); (S.B.)
| | - Shaik Fayaz Ahamed
- ICMR—National Institute for Research in Tuberculosis, Chennai 600031, India; (A.V.); (S.F.A.)
- National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai 600031, India; (A.N.); (N.S.); (K.M.); (R.M.R.); (S.B.)
| | - Rachel Marriam Renji
- National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai 600031, India; (A.N.); (N.S.); (K.M.); (R.M.R.); (S.B.)
| | - Kandasamy Sasidaran
- Dr. Mehta’s Children’s Hospital, Chennai 600031, India; (K.S.); (M.P.); (T.S.)
| | - Sandip Kumar
- Dr. Mehta’s Children’s Hospital, Chennai 600031, India; (K.S.); (M.P.); (T.S.)
| | | | | | - Poovazhagi Varadarajan
- Institute of Child Health and Hospital for Children, Chennai 600008, India; (P.V.); (E.C.)
| | - Elilarasi Chelladurai
- Institute of Child Health and Hospital for Children, Chennai 600008, India; (P.V.); (E.C.)
| | - Subash Babu
- National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai 600031, India; (A.N.); (N.S.); (K.M.); (R.M.R.); (S.B.)
- Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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Kapoor R, Chandra T, Singh CP, Singh R, Pandey I. Multisystem Inflammatory Syndrome in Children (MIS-C) Related to SARS-CoV-2 and 1-Year Follow-up. Indian J Pediatr 2023; 90:1008-1012. [PMID: 36482236 PMCID: PMC9734509 DOI: 10.1007/s12098-022-04385-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/18/2022] [Accepted: 09/12/2022] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To study the demographics, clinical profile, management, outcome and 1-y follow-up of children with multisystem inflammatory syndrome in children (MIS-C). METHODS This was a retrospective observational study of 54 Children satisfying the WHO MIS-C criteria admitted during the study period. RESULTS Fifty-four children were included in the study, median age was 5.5 (IQR 8.75), 68.5% were males. PICU admissions were 77%. Most involved organ was gastrointestinal (92%), followed by cardiovascular 85%, central nervous system (CNS) 74%, respiratory 72%, mucocutaneous 59%, and renal 31%, and hypotension was the presenting symptom in 43%. Coronary artery dilatation was seen in 1 (1.8%) child. All patients presented with more than three organs involvement. Raised procalcitonin was seen in 100%, raised BNP in 31.5%, low ejection fraction in 83.3%, and abnormal radiograph in 59%. All children were positive for anti-SARS-CoV-2 antibodies and negative for cultures. Methylprednisolone or intravenous immunoglobulin (IVIg) was used in 77%, mechanical ventilation in 18.5%, and inotropic support in 77%. Aspirin was used in 48% and low molecular weight heparin (LMWH) in 54%. The median stay in hospital was 7 d (IQR 2). There was 1 mortality (1.8%). On 7-d follow-up, 98% children had a normal echocardiography; on 6 mo and 1-y follow-up, all children had normal echocardiography. CONCLUSION MIS-C is an important complication of COVID-19 infection. Cardiac involvement resolves completely. Coronary artery involvement is not common.
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Affiliation(s)
- Rashmi Kapoor
- Department of Pediatrics, Regency Hospital, A-2, Sarvodaya Nagar, Kanpur, Uttar Pradesh, 208005, India.
| | - Tarun Chandra
- Department of Pediatrics, Regency Hospital, A-2, Sarvodaya Nagar, Kanpur, Uttar Pradesh, 208005, India
| | - Chandra Prakash Singh
- Department of Pediatrics, Regency Hospital, A-2, Sarvodaya Nagar, Kanpur, Uttar Pradesh, 208005, India
| | - Ruchira Singh
- Department of Pediatrics, Regency Hospital, A-2, Sarvodaya Nagar, Kanpur, Uttar Pradesh, 208005, India
| | - Ishita Pandey
- Department of Pediatrics, Regency Hospital, A-2, Sarvodaya Nagar, Kanpur, Uttar Pradesh, 208005, India
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Erdede Ö, Sari E, Külcü NU, Sezer Yamanel RG. The Role of Mean Platelet Volume in Multisystem Inflammatory Syndrome in Children With Cardiac Manifestations. Pediatr Infect Dis J 2023; 42:601-607. [PMID: 37054394 PMCID: PMC10289071 DOI: 10.1097/inf.0000000000003917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/17/2023] [Indexed: 04/15/2023]
Abstract
BACKGROUND Multisystem inflammatory syndrome in children (MIS-C) is a novel pediatric disorder associated with coronavirus disease 2019. However, no laboratory parameters can diagnose MIS-C. This study aimed to determine the changes in mean platelet volume (MPV) and investigate its relationship with cardiac involvement in MIS-C. METHODS In this single-center retrospective study, 35 children with MIS-C, 35 healthy children and 35 febrile children were enrolled. Patients with MIS-C were further subdivided depending on the presence of cardiac involvement. For all patients, the white blood cell, absolute neutrophil, absolute lymphocyte, platelet counts, MPV and C-reactive protein levels were recorded. Ferritin, D-dimer, troponin and CK-MB levels and the day when IVIG was administered were recorded and compared between groups. RESULTS Thirteen patients with MIS-C had cardiac involvement. The mean MPV of the MIS-C group was significantly higher than those of the healthy ( P = 0.0001) and febrile ( P = 0.027) groups. Using a cutoff of >7.6 fL, the MPV had a sensitivity of 82.86% and specificity of 82.75%, and the area under the MPV receiver operating characteristics curve was 0.896 (0.799-0.956). The MPV was significantly higher in patients with cardiac involvement than in those without ( P = 0.031). Logistic regression analysis revealed that the association between the MPV and cardiac involvement was significant (odds ratio, 2.28; 95% confidence interval, 1.04-2.95; P = 0 .039). CONCLUSIONS The MPV may indicate cardiac involvement in patients with MIS-C. Large cohort studies are needed to define an accurate cutoff value for the MPV.
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Affiliation(s)
- Özlem Erdede
- From the Department of Pediatrics, Zeynep Kamil Maternity and Children’s Disease Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Erdal Sari
- From the Department of Pediatrics, Zeynep Kamil Maternity and Children’s Disease Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Nihan U. Külcü
- From the Department of Pediatrics, Zeynep Kamil Maternity and Children’s Disease Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Rabia G. Sezer Yamanel
- From the Department of Pediatrics, Zeynep Kamil Maternity and Children’s Disease Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
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11
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Gupta S, Angurana SK, Kumar V. Respiratory Care in Children with COVID-19. J Pediatr Intensive Care 2023; 12:87-93. [PMID: 37082463 PMCID: PMC10113014 DOI: 10.1055/s-0041-1723036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 12/20/2020] [Indexed: 12/28/2022] Open
Abstract
The novel coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is causing significant morbidity and mortality worldwide. The common presentations in children include involvement of respiratory system leading to pneumonia and acute respiratory distress syndrome, as well as multiorgan dysfunction syndrome and multisystem inflammatory syndrome in children (MIS-C). Pediatric COVID-19 is a milder disease as compared with the adults. Also, there is rise in MIS-C cases which is a hyperinflammatory condition temporally associated with SARS-CoV-2. Since respiratory system is predominantly involved, few of these critically ill children often require respiratory support which can range from simple oxygen delivery devices, high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), invasive mechanical ventilation, and extracorporeal membrane oxygenation (ECMO). Most of the oxygen delivery devices and respiratory interventions generate aerosols and pose risk of transmission of virus to health care providers (HCPs). The use of HFNC and NIV should be limited to children with mild respiratory distress preferably in negative pressure rooms and with adequate personal protective equipment (PPE). However, there should be low thresholds for intubation and invasive mechanical ventilation in the event of clinical deterioration while on any respiratory support. The principle of providing respiratory support requires special droplet and air-borne precautions to limit exposure or transmission of virus to HCPs and at the same time ensuring safety of the patient.
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Affiliation(s)
- Shalu Gupta
- Department of Pediatric, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi, India
| | - Suresh K. Angurana
- Department of Pediatrics, Advanced Pediatrics Centre (APC), Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Virendra Kumar
- Department of Pediatric, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi, India
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12
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Ghimire LV, Chou FS, Aljohani OA, Moon-Grady AJ. Impact of congenital heart disease on outcomes among pediatric patients hospitalized for COVID-19 infection. BMC Pediatr 2023; 23:240. [PMID: 37194031 DOI: 10.1186/s12887-023-04058-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 05/04/2023] [Indexed: 05/18/2023] Open
Abstract
BACKGROUND COVID-19 infection is generally regarded as an acute self-limiting illness in children, but it can cause significant morbidity and mortality in both healthy and high-risk children. There are limited data on the outcomes of children with congenital heart disease (CHD) and COVID-19. This study aimed to examine the risks of mortality, in-hospital cardiovascular and non-cardiovascular complications in this patient population. METHODS We analyzed data from hospitalized pediatric patients from 2020 using the nationally representative National Inpatient Sample (NIS). Children hospitalized for COVID-19 were included, and weighted data were used to compare in-hospital mortality and morbidities between children with and without CHD. RESULTS Out of 36,690 children admitted with a diagnosis of COVID-19 infection(ICD-10 code:U07.1 and B97.29) during calendar year 2020, 1240 (3.4%) had CHD. The risk of mortality in children with CHD was not significantly higher than those without CHD(1.2% vs. 0.8%, p = 0.50), with adjusted OR (aOR) of 1.7 (95% CI: 0.6-5.3). Tachyarrhythmias and heart block were more likely in CHD children with an aOR of 4.2 (95% CI: 1.8-9.9) and aOR of 5.0 (95% CI: 2.4-10.8), respectively. Similarly, respiratory failure [aOR = 2.0 (1.5-2.8)], respiratory failure requiring non-invasive mechanical ventilation [aOR = 2.7 (1.4-5.2)] and invasive mechanical ventilation [aOR = 2.6 (1.6-4.0)], and acute kidney injury [aOR = 3.4 (2.2-5.4)] were all significantly higher among patients with CHD. Median length of hospital stay in children with CHD was longer than those without CHD [5 days (IQR: 2-11) vs. 3 days (IQR: 2-5), p = < 0.001]. CONCLUSIONS Children with CHD hospitalized with COVID-19 infection were at increased risk of serious cardiovascular and non-cardiovascular adverse clinical outcomes. They also had increased length of hospital stay and utilization of healthcare resources.
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Affiliation(s)
- Laxmi V Ghimire
- Division of Pediatric Cardiology, Department of Pediatrics, University of California, San Francisco, Fresno, CA, USA
| | - Fu-Sheng Chou
- Department of Neonatal-Perinatal Medicine, Kaiser Permanente Riverside Medical Center, Riverside, CA, USA
| | - Othman A Aljohani
- Division of Pediatric Cardiology, Department of Pediatrics, University of California, San Francisco, 550 16th Street 5th Floor, San Francisco, CA, 94158, USA
| | - Anita J Moon-Grady
- Division of Pediatric Cardiology, Department of Pediatrics, University of California, San Francisco, 550 16th Street 5th Floor, San Francisco, CA, 94158, USA.
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13
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Varadarajan P, Elilarasi S, Solomon RS, Subramani S, Subramanian R, Rangabashyam N, Srividya G. Multisystem Inflammatory Syndrome in Children (MIS-C) Associated With Covid-19 - Single-Center Experience. Indian Pediatr 2023; 60:389-390. [PMID: 36896751 PMCID: PMC10185933 DOI: 10.1007/s13312-023-2887-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 08/03/2022] [Accepted: 03/02/2023] [Indexed: 11/26/2023]
Abstract
OBJECTIVES To describe the clinical presentation, phenotype and outcome of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (Covid-19) from a tertiary care center in southern India. METHODS 257 children fulfilling the inclusion criteria of MIS-C were prospectively enrolled from June, 2020 to March, 2022. RESULTS Median (range) age at presentation was 6 year (35 day to 12 years). Presenting features were fever (98%), vomiting (75.8%), red eyes (63%), rashes (49%), pain abdomen (49%), shock (45.9%), lymphopenia (73%, thrombocytopenia (58.3%) and anemia (45%). 103 (39.7%) children required intensive care admission. Shock phenotype, Kawasaki-like phenotype and no specific phenotype were diagnosed in 45.9%, 44.4%, and 36.6% children, respectively. Left ventricular dysfunction (30.3%), acute kidney injury (13%), acute liver failure (17.4%), and hemophagolymphohistiocytosis (HLH) (13.6%) were the major system involvement in MIS-C. Mitral regurgitation (P=0.029), hyperechogenic coronaries (P=0.006), Left ventricular dysfunction (P=0.001) and low ejection fraction (P=0.007) were significantly associated with shock. Overall mortality was 11.7%. CONCLUSION Kawasaki-like and shock-like presentation were common in MIS-C. Coronary abnormalities were seen in 118 (45.9%) children. Children with acute kidney injury, HLH, need for mechanical ventilation, and echocardiogram evidence of mitral regurgitation in MIS-C have a poor outcome.
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Affiliation(s)
- Poovazhagi Varadarajan
- Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu. Correspondence to: Dr Poovazhagi Varadarajan, HOD and Professor, Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu.
| | - S Elilarasi
- Department of Pediatric Pulmonology, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu
| | - Ritchie Sharon Solomon
- Department of Pediatric Cardiology, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu
| | - Seenivasan Subramani
- Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu
| | - Ramesh Subramanian
- Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu
| | - Nisha Rangabashyam
- Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu
| | - Gomathy Srividya
- Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu
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Sobh A, Mosa DM, Khaled N, Korkor MS, Noureldin MA, Eita AM, Elnagdy MH, El-Bayoumi MA. How multisystem inflammatory syndrome in children discriminated from Kawasaki disease: a differentiating score based on an inception cohort study. Clin Rheumatol 2023; 42:1151-1161. [PMID: 36409406 PMCID: PMC9684855 DOI: 10.1007/s10067-022-06444-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 10/31/2022] [Accepted: 11/05/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND About 25-50% of multisystem inflammatory syndrome in children (MIS-C) patients meet the criteria for diagnosis of Kawasaki disease (KD). The differentiation of both conditions is so challenging on clinical practice as the management of both is time dependant and precise diagnosis is fundamental. METHOD Data were collected from children < 18 years old hospitalized with MIS-C or KD. Patient demographics, clinical, and laboratory data were compared, and a discrimination score was created to assist in clinical differentiation. RESULTS 72 patients with MIS-C and 18 with KD were included in the study. Patients with MIS-C had a higher prevalence of abdominal pain (p = 0.02), vomiting (p = 0.03), and cervical lymphadenopathy (p = 0.02) compared with KD cases. MIS-C patients had higher liver enzymes (aspartate aminotransferase (AST) (p = 0.04), alanine aminotransferase (ALT) (p = 0.03), serum creatinine (p = 0.03), and lower platelet count nadir (p = 0.02) than KD. Four variables were detected in the regression analysis model, and the independent predictors were utilized to generate a scoring model that distinguished MIS-C from KD with an area under the curve of 0.70. CONCLUSION This study constructed a prediction model for differentiation of MIS-C from KD based on clinical and laboratory profiles. This model will be valuable to guide clinicians in the treatment decisions. Key Points • Children with MIS-C are more likely to have gastrointestinal symptoms, cervical lymphadenopathy, and respiratory involvement than KD patients. • Elevated liver enzymes and lower platelet count are more pronounced laboratory findings in MIS-C than KD. • This study constructed a prediction model for differentiation of MIS-C from KD based on clinical and laboratory profiles. This model will be valuable to guide clinicians in the treatment decisions.
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Affiliation(s)
- Ali Sobh
- Department of Pediatrics, Mansoura University Children's Hospital, Mansoura University Faculty of Medicine, Mansoura, Egypt
| | - Doaa Mosad Mosa
- Rheumatology & Rehabilitation Department, Mansoura University Hospitals, Mansoura University Faculty of medicine , 60 Elgomhoria St, Mansoura, 35516, Egypt.
| | - Nada Khaled
- Department of Clinical Pathology (Hematology Unit), Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mai S Korkor
- Department of Pediatrics, Mansoura University Children's Hospital, Mansoura University Faculty of Medicine, Mansoura, Egypt
| | | | - Ahmad M Eita
- Department of Pediatrics, Mansoura University Children's Hospital, Mansoura University Faculty of Medicine, Mansoura, Egypt
| | - Marwa H Elnagdy
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mohammed A El-Bayoumi
- Department of Pediatrics, Mansoura University Children's Hospital, Mansoura University Faculty of Medicine, Mansoura, Egypt
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Tripathi AK, Pilania RK, Bhatt GC, Atlani M, Kumar A, Malik S. Acute kidney injury following multisystem inflammatory syndrome associated with SARS-CoV-2 infection in children: a systematic review and meta-analysis. Pediatr Nephrol 2023; 38:357-370. [PMID: 35943577 PMCID: PMC9362633 DOI: 10.1007/s00467-022-05701-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 07/19/2022] [Accepted: 07/20/2022] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Multisystem inflammatory syndrome (MIS-C) is a rare paediatric hyper-inflammatory disorder that occurs following SARS-CoV-2 infection. Acute kidney injury (AKI) occurs in approximately one-quarter to one-third of the patients with MIS-C and is associated with poor prognosis in critically ill children. This systematic review is aimed to evaluate the incidence of AKI, mortality, and the need for kidney replacement therapy (KRT) in patients with MIS-C. METHODS We searched databases from Medline, EMBASE, Cochrane Register, and Google Scholar from December 2019 to December 2021 with our search strategy. Studies meeting the following criteria were included in this systematic review: (1) articles on AKI in MIS-C; (2) studies providing AKI in MIS-C and COVID-19 infection separately; (3) studies reporting outcomes such as mortality, KRT, serum creatinine; length of hospital/ICU stay. QUALITY ASSESSMENT The quality of the included studies was independently assessed by using the National Heart Lung and Blood Institute (NHLBI) quality assessment tool for cohort studies and case series. STATISTICAL ANALYSIS Outcomes and their 95% confidence intervals (CI) were reported if a meta-analysis of these outcomes was conducted. Heterogeneity was reported using I2 statistics, and heterogeneity ≥ 50% was considered high. We used Baujat's plot for the contribution of each study toward overall heterogeneity. In sensitivity analysis, the summary estimates were assessed by repeating meta-analysis after omitting one study at a time. Forest plots were used for reporting outcomes in each study and with their 95% CI. All statistical tests were performed using R software version 4.0.3. RESULTS A total of 24 studies were included in this systematic review and of these, 11 were included in the meta-analysis. The pooled proportion of patients with MIS-C developing AKI was 20% (95% CI: 14-28%, I2 = 80%). Pooled proportion of death in children with MIS-C was 4% (95% CI: 1-14%; I2 = 93%). The odds of death in patients with AKI were 4.68 times higher than in patients without AKI (95% CI: 1.06-20.7%; I2 = 17%). The overall pooled proportion of MIS-C-induced AKI patients requiring KRT was 15% (95% CI: 4-42%; I2 = 91%). CONCLUSION Approximately one-fifth of children with MIS-C develop AKI which is associated with higher odds of death. PROSPERO registration: CRD42022306170 A higher resolution version of the Graphical abstract is available as Supplementary information.
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Affiliation(s)
- Anchal Kumar Tripathi
- Department of Pediatrics, ISN-SRC, All India Institute of Medical Sciences (AIIMS), Room no 1023, Academic Block, Saket Nagar, Bhopal, MP, 462024, India
| | - Rakesh Kumar Pilania
- Advanced Pediatrics Centre, Division of Clinical Immunology and Rheumatology, Post Graduate Institute of Medical Sciences (PGI), Chandigarh, India
| | - Girish Chandra Bhatt
- Department of Pediatrics, ISN-SRC, All India Institute of Medical Sciences (AIIMS), Room no 1023, Academic Block, Saket Nagar, Bhopal, MP, 462024, India.
| | - Mahendra Atlani
- Department of Nephrology, All India Institute of Medical Sciences (AIIMS), Bhopal, MP, India
| | - Amber Kumar
- Department of Pediatrics, ISN-SRC, All India Institute of Medical Sciences (AIIMS), Room no 1023, Academic Block, Saket Nagar, Bhopal, MP, 462024, India
| | - Shikha Malik
- Department of Pediatrics, ISN-SRC, All India Institute of Medical Sciences (AIIMS), Room no 1023, Academic Block, Saket Nagar, Bhopal, MP, 462024, India
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Sai BVK, Kumar H, Arun Babu T, Chaitra R, Satapathy D, Kalidoss VK. Clinical profile and outcome of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection: a single-center observational study from South India. EGYPTIAN PEDIATRIC ASSOCIATION GAZETTE 2023. [PMCID: PMC9867992 DOI: 10.1186/s43054-022-00156-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Abstract
Background
Multisystem inflammatory syndrome in children (MIS-C) is a post-infectious sequelae of acute COVID-19 infection affecting children. This study was done over a period of 12 months from December 2020 to November 2021 to describe the clinical presentation, laboratory abnormalities, and outcome of children with MIS-C.
Methods
Seventy-eight children below 12 years of age who satisfied the WHO diagnostic criteria for MIS-C were included in the study. Clinical parameters were recorded at admission. Relevant laboratory investigations, radiological studies, and outcome were documented.
Results
The most commonly affected age group was 6–12 years with a female predominance. COVID RTPCR was negative in all patients. Most cases presented 2–6 weeks after the onset of acute COVID-19 infection. Lethargy, poor feeding, vomiting, abdominal pain, loose stools, cough, and cold are common symptoms of MIS-C syndrome in children and the common signs were rash, conjunctival congestion, hypotension, tachycardia, tachypnea, and hypoxemia. Gastrointestinal system was the commonly affected followed by the hepatic, renal, and cardiovascular systems. Coronary artery abnormalities were seen in 20% of cases. IVIg was the mainstay of therapy used in 95% of patients. Mortality was 1.3%. Cases responded well to IVIg and steroids.
Conclusion
Overall, the short-term outcome was favorable with low mortality in our study cohort. One-fifth of children had coronary artery abnormalities during acute phase underscoring the need for long-term follow-up.
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Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 Infection in KwaZulu-Natal, South Africa. Pediatr Infect Dis J 2023; 42:e9-e14. [PMID: 36476527 PMCID: PMC9725742 DOI: 10.1097/inf.0000000000003759] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Multisystem inflammatory syndrome in children (MIS-C) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been infrequently described in Africa. OBJECTIVE To describe the clinical characteristics, outcomes and associations of severe disease in children hospitalized with MIS-C in KwaZulu-Natal. METHODS Retrospective multicenter study of children (0-13 years) who met the Centers for Disease Control and Prevention criteria for MIS-C. Children with shock were compared with children without shock to determine the characteristics of severe MIS-C. RESULTS Twenty-nine children with MIS-C were identified, the mean age was 55 (SD ±45) months, 25 (86%) were Black-African, and 8 (28%) had pre-existing comorbidities. The predominant presenting symptoms included fever 29 (100%), gastrointestinal symptoms 25 (83%), skin rash 19 (65%), and shock 17 (59%). Children with shock had significantly increased CRP (P = 0.01), ferritin (P < 0.001), troponin-T (P = 0.02), B-type natriuretic peptide (BNP) (P = 0.01), and lower platelets (P = 0.01). Acute kidney injury (P = 0.01), cardiac involvement (P = 0.02), and altered levels of consciousness (P = 0.03) were more common in children with shock. The median length of hospital stay was 11 (IQR 7-19) days, with a mortality of 20.6%. Children who did not survive had significantly higher ferritin levels 1593 (IQR 1069-1650) ng/mL versus 540 (IQR 181-1156) ng/mL; P = 0.03) and significantly more required mechanical ventilation (OR 18; confidence interval 1.7-191.5; P = 0.005). CONCLUSIONS Hospitalized children with MIS-C in KwaZulu-Natal had more aggressive disease and higher mortality than children in better-resourced settings. Markedly elevated biomarkers and critical organ involvement were associated with severe disease. Risk factors for poor outcomes include higher ferritin levels and the need for mechanical ventilation.
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18
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Ganguly M, Gupta P, Biswas D, Sarkar SD, Pal P. Multisystem Inflammatory Syndrome in Children (MIS-C): Comparison of the First and the Second Waves. Indian Pediatr 2023; 60. [PMID: 36639974 PMCID: PMC9885396 DOI: 10.1007/s13312-023-2699-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
This study comparing the different parameters of children suffering from multisystem inflammatory syndrome in children (MIS-C) in Kolkata, India, during the two waves (July, 2020-January, 2021 and April-July, 2021) showed that the second wave had a higher propensity of Kawasaki disease (KD)-like presentation, cardiac affection and pediatric intensive care unit admission, and increased incidence of use of steroids for treatment.
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Affiliation(s)
- Mimi Ganguly
- Pediatric Rheumatology Unit, Institute of Child Health, Kolkata, West Bengal India
| | - Purbasha Gupta
- Pediatric Rheumatology Unit, Institute of Child Health, Kolkata, West Bengal India
| | - Debopama Biswas
- Pediatric Rheumatology Unit, Institute of Child Health, Kolkata, West Bengal India
| | - Subhajit Dey Sarkar
- Pediatric Rheumatology Unit, Institute of Child Health, Kolkata, West Bengal India
| | - Priyankar Pal
- Pediatric Rheumatology Unit, Institute of Child Health, Kolkata, West Bengal India
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19
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Karunakar P, Ramamoorthy JG, Anantharaj A, Parameswaran N, Biswal N, Dhodapkar R, Bhaskar M, Basu D, Das S, Gunalan A. Clinical profile and outcomes of multisystem inflammatory syndrome in children (MIS-C): Hospital-based prospective observational study from a tertiary care hospital in South India. J Paediatr Child Health 2022; 58:1964-1971. [PMID: 35869845 DOI: 10.1111/jpc.16129] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 05/15/2022] [Accepted: 07/06/2022] [Indexed: 11/28/2022]
Abstract
AIM To study the clinical profile and outcomes in children with multisystem inflammatory syndrome in children (MIS-C). METHODS Children aged 1 month to 15 years presenting with MIS-C (May 2020 to November 2021) were enrolled. Clinical, laboratory, echocardiography parameters and outcomes were analysed. RESULTS Eighty-one children (median age 60 months (24-100)) were enrolled. Median duration of fever was 5 days (3-7). Twenty-nine (35.8%) had shock (severe MIS-C) including 23 (28.3%) requiring inotropes (median duration = 25 h (7.5-33)). Ten required mechanical ventilation, 12 had acute kidney injury and 1 child died. Left ventricular (LV) dysfunction was seen in 38 (46.9%), 16 (19.7%) had coronary artery abnormalities (CAA) and 13 (20%) had macrophage activation syndrome. Sixty-one (75.3%) were SARS CoV-2 positive (10 by RT-PCR and 51 by serology). Sixty-eight (83.9%) received immunomodulators. Younger age was significantly associated with CAA (P value = 0.05). Older age, LV dysfunction, SARS CoV-2 positivity, low platelet count and elevated serum ferritin were significantly associated with severe MIS-C (univariate analysis). Younger age was an independent predictor of CAA (P = 0.05); older age (P = 0.043) and low platelet count (P = 0.032) were independent predictors of severe MIS-C (multivariate logistic regression analysis). CONCLUSION Our patients had diverse clinical manifestations with a good outcome. Younger age was significantly associated with CAA. Older age, LV dysfunction, low platelet count and elevated serum ferritin were significantly associated with severe MIS-C. Younger age is an independent predictor of CAA. Older age and low platelet count are independent predictors of severe MIS-C.
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Affiliation(s)
- Pediredla Karunakar
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Jaikumar G Ramamoorthy
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Avinash Anantharaj
- Department of Cardiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Narayanan Parameswaran
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Niranjan Biswal
- Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Rahul Dhodapkar
- Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Maanasa Bhaskar
- Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Debdatta Basu
- Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Sindhusuta Das
- Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
| | - Anitha Gunalan
- Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India
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Sugunan S, Bindusha S, Niyas HR, Geetha S, Chinchilu RV. Factors Associated with Pulse Methylprednisolone Treatment Failure in COVID-19-Related Multisystem Inflammatory Syndrome in Children (MIS-C). J PEDIAT INF DIS-GER 2022. [DOI: 10.1055/s-0042-1755210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
Abstract
Objective This article determines the occurrence and variables associated with pulse methylprednisolone treatment failure in children with coronavirus disease 2019 (COVID-19)-related multisystem inflammatory syndrome in children (MIS-C).
Methods This prospective observational study was undertaken at a tertiary care teaching hospital in Kerala, India. Children admitted with COVID-19-related MIS-C who were treated with pulse methylprednisolone as first-line therapy were included in the study. Depending on the response to the treatment, they were divided into two groups. The clinical, laboratory parameters, and follow-up findings at 3 months were compared between the two groups
Results Seventy-six patients were admitted with MIS-C during the study period. Sixty received pulse methylprednisolone as the first-line therapy. Of the 60 patients who received pulse methylprednisolone, 50 responded to treatment, while 10 required repeat immunomodulation. Need for noninvasive or invasive ventilation (relative risk [RR]: 13.14, 95% confidence interval [CI]: 3.147–54.88), six or more organ involvement (RR: 4.667, 95% CI: 1.349–16.149), thrombocytopenia (RR: 6.43, 95% CI: 0.87–47.6, p 0.003), and abnormal chest X-ray findings at admission (RR: 4.5, 95% CI: 1.46–13.8), were found to be associated with increased risk of treatment failure with pulse methylprednisolone therapy. Note that 88% of patients with coronary artery involvement showed resolution at 3-month follow-up.
Conclusion More than 80% of children with MIS-C can be treated successfully with corticosteroids. The need for ventilator support, abnormal chest X-ray findings, and thrombocytopenia at admission were found to be factors associated with pulse methylprednisolone treatment failure.
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Affiliation(s)
- Sheeja Sugunan
- Department of Paediatrics, Government Medical College Thiruvananthapuram, Thiruvananthapuram, Kerala, India
| | - S. Bindusha
- SAT Hospital, Government Medical College, Thiruvananthapuram, Kerala, India
| | - H. R. Niyas
- SAT Hospital, Government Medical College, Thiruvananthapuram, Kerala, India
| | - S. Geetha
- SAT Hospital, Government Medical College, Thiruvananthapuram, Kerala, India
| | - R V Chinchilu
- SAT Hospital, Government Medical College, Thiruvananthapuram, Kerala, India
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21
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Mishra B, Mishra B, Mohapatra A, Patwari V, Malini SD, Panda M, Swain S. Clinical Profile and Outcomes of Multisystem Inflammatory Syndrome in Children: A Multicentric Observational Study. Cureus 2022; 14:e28821. [PMID: 36225458 PMCID: PMC9535389 DOI: 10.7759/cureus.28821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2022] [Indexed: 11/05/2022] Open
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22
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Elilarasi S, Poovazhagi V, Kumaravel G, Srividya VG, Solomon JRS. Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2. Indian J Pediatr 2022; 89:879-884. [PMID: 34817811 PMCID: PMC8611247 DOI: 10.1007/s12098-021-03954-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Accepted: 07/07/2021] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To know the clinical presentation and outcome of children with pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV- 2 (PIMS-TS) at a pediatric tertiary care center in Chennai. METHODS Clinical and biochemical parameters of 65 children with PIMS-TS treated between July and October 2020 were studied. All children had their COVID RT-PCR and IgG COVID antibodies tests done. RESULTS Mean age of the study group was 5.65 ± 3.68 y. Fever with red eyes, rash, vomiting, abdominal pain, and shock were common presenting features. Sixty percent of the study group had Kawasaki/incomplete Kawasaki features. Sixty-seven percent of the study group had coronary dilatation, 41% presented with shock, and 25% had left ventricular dysfunction. Coronary aneurysms were documented in 58% of the study group (z score more than 2.5). Respiratory presentation with pneumonia was seen in 10%. Four children presented with acute abdomen. Acute kidney injury, acute liver failure, hemolysis, pancytopenia, macrophage activation syndrome, encephalopathy, and multiorgan dysfunction syndrome (MODS) were other features. Forty-three percent required noninvasive oxygen support and 15.4% required mechanical ventilation. Intravenous immunoglobulin (73.8%) and methylprednisolone (49.8%) were used for therapy. Mortality in the study was 6%, which was due to MODS. CONCLUSIONS Acute febrile illness with mucocutaneous and gastrointestinal manifestations should have PIMS-TS as a possible differential diagnosis and needs evaluation with inflammatory markers and SARS-CoV-2 antibodies.
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Affiliation(s)
- S Elilarasi
- Department of Pediatrics, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu, 600008, India
| | - V Poovazhagi
- HOD & Professor, Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu, India
| | - G Kumaravel
- Department of Pediatrics, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu, 600008, India
| | - V Gomathy Srividya
- Department of Pediatrics, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu, 600008, India.
| | - J Ritchie Sharon Solomon
- Department of Pediatric Cardiology, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu, India
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23
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Angurana SK, Kumar V, Nallasamy K, Kumar MR, Naganur S, Kumar M, Goyal K, Ghosh A, Bansal A, Jayashree M. Clinico-Laboratory Profile, Intensive Care Needs and Short-Term Outcome of Multisystem Inflammatory Syndrome in Children (MIS-C): Experience during First and Second Waves from North India. J Trop Pediatr 2022; 68:6680455. [PMID: 36048462 DOI: 10.1093/tropej/fmac068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
OBJECTIVES To describe the clinico-laboratory profile, intensive care needs and outcome of multisystem inflammatory syndrome in children (MIS-C) during the first and second waves. METHODOLOGY This retrospective study was conducted in the paediatric emergency and paediatric intensive care unit (PICU) of a tertiary care teaching hospital in North India involving 122 children with MIS-C admitted during the first wave (September 2020-January 2021, n = 40) and second wave (February 2021-September 2021, n = 82) of coronavirus disease 2019 (COVID-19). RESULTS The median (interquartile range) age was 7 (4-10) years and 67% were boys. Common manifestations included fever (99%), abdominal symptoms (81%), rash (66%) and conjunctival injection (65%). Elevated C-reactive protein (97%), D-dimer (89%), procalcitonin (80%), IL-6 (78%), ferritin (56%), N-terminal pro B-type natriuretic peptide (84%) and positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody (81%) were common laboratory abnormalities. Cardiovascular manifestations included myocardial dysfunction (55%), shock (48%) and coronary artery changes (10%). The treatment included intensive care support (57%), non-invasive (33%) and invasive (18%) ventilation, vasoactive drugs (47%), intravenous immunoglobulin (IVIG) (83%), steroids (85%) and aspirin (87%). The mortality was 5% (n = 6). During the second wave, a significantly higher proportion had positive SARS-CoV-2 antibody, contact with COVID-19 and oral mucosal changes; lower markers of inflammation; lower proportion had lymphopenia, elevated IL-6 and ferritin; lower rates of shock, myocardial dysfunction and coronary artery changes; lesser need of PICU admission, fluid boluses, vasoactive drugs and IVIG; and shorter hospital stay. CONCLUSION MIS-C is a febrile multisystemic disease characterized by hyperinflammation, cardiovascular involvement, temporal relationship to SARS-CoV-2 and good outcome with immunomodulation and intensive care. During the second wave, the severity of illness, degree of inflammation, intensive care needs, and requirement of immunomodulation were less as compared to the first wave.
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Affiliation(s)
- Suresh Kumar Angurana
- Division of Pediatric Emergency and Intensive Care, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Vijay Kumar
- Division of Pediatric Emergency and Intensive Care, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Karthi Nallasamy
- Division of Pediatric Emergency and Intensive Care, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Manoj Rohit Kumar
- Department of Cardiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Sanjeev Naganur
- Department of Cardiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Mahendra Kumar
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Kapil Goyal
- Department of Virology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Arnab Ghosh
- Department of Virology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Arun Bansal
- Division of Pediatric Emergency and Intensive Care, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
| | - Muralidharan Jayashree
- Division of Pediatric Emergency and Intensive Care, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
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24
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McDaniel CG, Commander SJ, DeLaura I, Cantrell S, Leraas HJ, Moore CB, Reed CR, Pahl KS, Tracy ET. Coagulation Abnormalities and Clinical Complications in Children With SARS-CoV-2: A Systematic Review of 48,322 Patients. J Pediatr Hematol Oncol 2022; 44:323-335. [PMID: 34862349 DOI: 10.1097/mph.0000000000002321] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 07/07/2021] [Indexed: 02/03/2023]
Abstract
Given the limited information on the coagulation abnormalities of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in pediatric patients, we designed a systematic review to evaluate this topic. A comprehensive literature search was conducted for "SARS-CoV-2," "coagulopathy," and "pediatrics." Two authors independently screened the articles that the search returned for bleeding, thrombosis, anticoagulant and/or antiplatelet usage, and abnormal laboratory markers in pediatric patients with SARS-CoV-2, and the authors then extracted the relevant data. One hundred twenty-six publications were included. Thirty-four (27%) studies reported thrombotic complications in 504 patients. Thirty-one (25%) studies reported bleeding complications in 410 patients. Ninety-eight (78%) studies reported abnormal laboratory values in 6580 patients. Finally, 56 (44%) studies reported anticoagulant and/or antiplatelet usage in 3124 patients. The variety of laboratory abnormalities and coagulation complications associated with SARS-CoV-2 presented in this review highlights the complexity and variability of the disease presentation in infants and children.
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Affiliation(s)
| | | | | | - Sarah Cantrell
- Duke University School of Medicine
- Duke University Medical Center Library and Archives, Durham, NC
| | | | | | | | - Kristy S Pahl
- Division of Pediatric Hematology-Oncology
- Department of Pediatrics
| | - Elisabeth T Tracy
- Department of Surgery
- Division of Pediatric Surgery, Duke University Medical Center
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25
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Stafie CS, Solomon SM, Sufaru IG, Manaila M, Stafie II, Melinte G, Simionescu B, Leustean L. Pathogenic Connections in Post-COVID Conditions: What Do We Know in the Large Unknown? A Narrative Review. Viruses 2022; 14:1686. [PMID: 36016309 PMCID: PMC9413998 DOI: 10.3390/v14081686] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 07/27/2022] [Accepted: 07/27/2022] [Indexed: 11/17/2022] Open
Abstract
The coronavirus 2019 (COVID-19) disease has long-term effects, known as post-COVID conditions (PCC) or long-COVID. Post-COVID-19 syndrome is defined by signs and symptoms that occur during or after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which persist for more than 12 weeks and cannot be supported by an alternative diagnosis. The cardiovascular damage caused by COVID-19 in the severe forms of the disease is induced by severe systemic inflammation, considered to be one of the causes of myocardial lesions, with increased levels of circulating cytokines and toxic response mediators. We have focused on conditions that can induce long-COVID-19, or multisystem inflammatory syndrome in adults or children (MIS-C/MIS-A), with an emphasis on endocrinological and metabolic disorders. Although described less frequently in children than in adults, long-COVID syndrome should not be confused with MIS-C, which is an acute condition characterized by multisystem involvement and paraclinical evidence of inflammation in a pediatric patient who tested positive for SARS-CoV-2. At the same time, we mention that the MIS-A symptoms remit within a few weeks, while the duration of long-COVID is measured in months. Long-COVID syndrome, along with its complications, MIS-A and MIS-C, represents an important challenge in the medical community. Underlying comorbidities can expose both COVID-19 adult and pediatric patients to a higher risk of negative outcomes not only during, but in the aftermath of the SARS-CoV-2 infection as well.
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Affiliation(s)
- Celina Silvia Stafie
- Department of Preventive Medicine and Interdisciplinarity—Family Medicine Discipline, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania;
| | - Sorina Mihaela Solomon
- Department of Periodontology, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700111 Iasi, Romania
| | - Irina-Georgeta Sufaru
- Department of Periodontology, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700111 Iasi, Romania
| | - Maria Manaila
- Endocrinology Residency Program, Sf. Spiridon Clinical Emergency Hospital, Independentei, 1, 700111 Iasi, Romania; (M.M.); (I.I.S.); (G.M.)
| | - Ingrid Ioana Stafie
- Endocrinology Residency Program, Sf. Spiridon Clinical Emergency Hospital, Independentei, 1, 700111 Iasi, Romania; (M.M.); (I.I.S.); (G.M.)
| | - Gabriela Melinte
- Endocrinology Residency Program, Sf. Spiridon Clinical Emergency Hospital, Independentei, 1, 700111 Iasi, Romania; (M.M.); (I.I.S.); (G.M.)
| | - Bianca Simionescu
- Pediatric Clinic No. 2, Mother and Child Department, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Victor Babes, 400347 Cluj-Napoca, Romania;
| | - Letitia Leustean
- Department of Endocrinology, Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania;
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Santos MO, Gonçalves LC, Silva PAN, Moreira ALE, Ito CRM, Peixoto FAO, Wastowski IJ, Carneiro LC, Avelino MAG. Multisystem inflammatory syndrome (MIS-C): a systematic review and meta-analysis of clinical characteristics, treatment, and outcomes. J Pediatr (Rio J) 2022; 98:338-349. [PMID: 34863701 PMCID: PMC9432310 DOI: 10.1016/j.jped.2021.08.006] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 08/27/2021] [Accepted: 10/28/2021] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE The clinical cases of patients with multisystem inflammatory syndrome (MIS-C) were analyzed via a systematic review and meta-analysis of the clinical findings, treatments, and possible outcomes of articles retrieved via database searches. SOURCES The authors searched the PubMed, Scielo, Web of Science, Science Direct, EMBASA, EBSCO, and Scopus databases for articles containing the keywords "multisystem inflammatory syndrome in children" or "MIS-C" or "PIMS-TS" or "SIMP" and "COVID-19" or "SARS-CoV-2" published between December 1st, 2019 and July 10th, 2021. Patient characteristics, tissue and organ comorbidities, the incidence of symptoms after COVID-19 infection, treatment, and patient evolution in the articles found were evaluated. The data were abstracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Newcastle-Ottawa Scale (NOS). FINDINGS In total, 98 articles (2275 patients) were selected for demographics, clinical treatment, and outcomes of patients diagnosed with MIS-C. The average age of children with MIS-C, 56.8% of whom were male, was of nine years. Fever (100%), gastrointestinal (GI) (82%), and abdominal pain (68%) were the decisive symptoms for the diagnosis of MIS-C. Shock and/or hypotension were common in patients with MIS-C. Cardiac symptoms (66%) predominated over respiratory (39%) and neurological (28%) symptoms. MIS-C treatment followed the common guidelines for treating children with septic shock and Kawasaki disease (KD) and proved to be effective. CONCLUSIONS This meta-analysis highlights the main clinical symptoms used for the diagnosis of MIS-C, the differences between MIS-C and KD, and the severity of the inflammatory process and urgency for hospital care.
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Affiliation(s)
- Mônica O Santos
- Universidade Federal de Goiás, Patologia Clínica e Medicina, Goiânia, GO, Brazil.
| | - Lucas C Gonçalves
- Universidade Federal de Goiás, Faculdade de Medicina, Goiânia, GO, Brazil
| | - Paulo A N Silva
- Universidade Federal de Goiás, Faculdade de Medicina, Goiânia, GO, Brazil
| | - André L E Moreira
- Universidade Federal de Goiás, Instituto de Patologia Tropical e Saúde Pública, Goiânia, GO, Brazil
| | - Célia R M Ito
- Universidade Federal de Goiás, Instituto de Patologia Tropical e Saúde Pública, Goiânia, GO, Brazil
| | | | - Isabela J Wastowski
- Universidade Federal de Goiás, Laboratório de Imunologia Molecular, Goiânia, GO, Brazil
| | - Lilian C Carneiro
- Universidade Federal de Goiás, Instituto de Patologia Tropical e Saúde Pública, Goiânia, GO, Brazil
| | - Melissa A G Avelino
- Universidade Federal de Goiás, Departamento de Pediatria, Goiânia, GO, Brazil
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Multisystem Inflammatory Syndrome Associated With COVID-19 in Children (MIS-C): A Systematic Review of Studies From India. Indian Pediatr 2022. [PMID: 35869878 PMCID: PMC9379896 DOI: 10.1007/s13312-022-2559-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Melo MM, Neta MMR, Neto ARS, Carvalho ARB, Magalhães RLB, Valle ARMC, Ferreira JHL, Aliaga KMJ, Moura MEB, Freitas DRJ. Symptoms of COVID-19 in children. Braz J Med Biol Res 2022; 55:e12038. [PMID: 35703681 PMCID: PMC9200047 DOI: 10.1590/1414-431x2022e12038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Accepted: 04/20/2022] [Indexed: 11/22/2022] Open
Abstract
The aim of this study was to review the symptomatic manifestations of COVID-19 in children in the scientific literature. An integrative review of studies published between December 2019 and September 5, 2021, from the Medical Literature Analysis and Retrieval System Online, Web of Science, Scopus, Literatura Latino-Americana em Ciência de Saúde, and Base de Dados de Enfermagem databases, was carried out to answer the following research question: What symptomatic manifestations does COVID-19 cause in children?". Twenty articles were included. The main symptoms described were fever, cough, diarrhea, vomiting, sore throat, dyspnea, headache, abdominal pain, malaise, and weakness or tiredness. The findings of this review can contribute to the diagnosis and clinical decision-making of the health team by providing information that facilitates the identification of COVID-19 in the target population, favoring early identification, better care, and consequently a better prognosis.
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Affiliation(s)
- M M Melo
- Programa de Pós-Graduação em Enfermagem, Departamento de Enfermagem, Universidade Federal do Piauí, Campus Universitário Ministro Petrônio Portella, Teresina, PI, Brasil
| | - M M R Neta
- Programa de Pós-Graduação em Enfermagem, Departamento de Enfermagem, Universidade Federal do Piauí, Campus Universitário Ministro Petrônio Portella, Teresina, PI, Brasil
| | - A R S Neto
- Departamento de Enfermagem, Universidade Federal do Piauí, Campus Universitário Ministro Petrônio Portella, Teresina, PI, Brasil
| | - A R B Carvalho
- Programa de Pós-Graduação em Enfermagem, Departamento de Enfermagem, Universidade Federal do Piauí, Campus Universitário Ministro Petrônio Portella, Teresina, PI, Brasil
| | - R L B Magalhães
- Programa de Pós-Graduação em Enfermagem, Departamento de Enfermagem, Universidade Federal do Piauí, Campus Universitário Ministro Petrônio Portella, Teresina, PI, Brasil
| | - A R M C Valle
- Programa de Pós-Graduação em Enfermagem, Departamento de Enfermagem, Universidade Federal do Piauí, Campus Universitário Ministro Petrônio Portella, Teresina, PI, Brasil
| | - J H L Ferreira
- Programa de Pós-Graduação em Ciências e Saúde, Universidade Federal do Piauí, Campus Universitário Ministro Petrônio Portella, Teresina, PI, Brasil
| | - K M J Aliaga
- Programa de Pós-Graduação em Enfermagem, Departamento de Enfermagem, Universidade Federal do Piauí, Campus Universitário Ministro Petrônio Portella, Teresina, PI, Brasil
| | - M E B Moura
- Programa de Pós-Graduação em Enfermagem, Departamento de Enfermagem, Universidade Federal do Piauí, Campus Universitário Ministro Petrônio Portella, Teresina, PI, Brasil
| | - D R J Freitas
- Programa de Pós-Graduação em Enfermagem, Departamento de Enfermagem, Universidade Federal do Piauí, Campus Universitário Ministro Petrônio Portella, Teresina, PI, Brasil
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Diggikar S, Nanjegowda R, Kumar A, Kumar V, Kulkarni S, Venkatagiri P. Neonatal Multisystem Inflammatory Syndrome secondary to SARS-CoV-2 infection. J Paediatr Child Health 2022; 58:900-902. [PMID: 34388280 PMCID: PMC8447297 DOI: 10.1111/jpc.15696] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 07/15/2021] [Accepted: 07/23/2021] [Indexed: 01/03/2023]
Affiliation(s)
- Shivshankar Diggikar
- Department of NeonatologyChinmay Mission HospitalBengaluruIndia,Department of NeonatologyOvum Woman and Child Speciality HospitalBengaluruIndia
| | | | - Ajay Kumar
- Department of NeonatologyChinmay Mission HospitalBengaluruIndia
| | - Vimal Kumar
- Department of NeonatologyChinmay Mission HospitalBengaluruIndia
| | - Srikant Kulkarni
- Department of NeonatologyChinmay Mission HospitalBengaluruIndia,Department of NeonatologyOvum Woman and Child Speciality HospitalBengaluruIndia
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Chattopadhyay A, Saigal Kalra K, Saikia D, Yadav V, Chouksey J, Jajoo M, Sherwal BL. Severe Multi-inflammatory Syndrome in Children Temporally Related to COVID 19-Clinical Course, Laboratory Profile and Outcomes from a North Indian PICU. J Intensive Care Med 2022; 37:1229-1237. [PMID: 35469487 DOI: 10.1177/08850666221092302] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Objective: We describe the trajectory of clinical course, laboratory markers and outcomes in children with severe multi-inflammatory syndrome temporally related to COVID-19 (MIS-C) admitted to our pediatric intensive care unit (PICU). Methods: This was a prospective case series of children admitted to PICU between May 1, 2020 and January 31, 2021, fulfilling the case definition of MIS-C published by World Health Organization (WHO) or Centers for Disease Control and Prevention (CDC). We analyzed demographic, clinical, laboratory data and echocardiographic findings. We also plotted the variation in trends between survivors and nonsurvivors. Results: Of the 34 critically ill children referred to PICU with diagnosis of MIS-C only 17 fulfilled the WHO/CDC classification of MIS-C, rest were MISC mimickers albeit other tropical infections. Median age at admission was 4 years (range 1y 6 mo-8 years). Fever, rash and conjunctival redness were most prominent symptoms. Myocardial involvement was seen in 70.5% while 76.4% developed shock; Invasive mechanical ventilation was required in 64.7% cases. Inflammatory markers showed a downward trend such as-median C- reactive protein (mg/L) had a serial reduction in levels-from (median/IQR) 210 (132.60, 246.90) at admission to 52.3 (42, 120) on Day 3. Median Ferritin (ng/ml) (n = 12) was 690 (203, 1324), serum LDH (IU/L) (n = 12) was 505 (229.5, 1032) and Mean D-dimer (ng/ml) (n = 7) was 5093.85 (1991.65), suggestive of hyperinflammatory syndrome. Twelve patients received intravenous immune globulin, with adjunctive steroid therapy used in two third of the cases. Six children died, 4 of them were under-5 years of age. Tocilizumab was prescribed in two children with high vasotrope inotrope score (VIS), cardiogenic shock and oxygenation index more than 15, both survived. Conclusions: Severe MIS-C has a heterogenous presentation, local or regional outbreaks of prevalent infectious diseases often lead to confusion and overdiagnosis. Higher proportion of mortality was seen in Under -5 children with MISC. Shock-like presentation, presence of myocardial dysfunction or nonsurvivor status is associated with higher trend of inflammatory markers and more profound multi-organ dysfunction. If disease progresses rapidly despite first line therapy (IvIg and steroids), use of Tocilizumab should be considered-as a rescue therapy under resource limitations in the absence of extracorporeal support.
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Affiliation(s)
- Arpita Chattopadhyay
- Department of Pediatrics, 75299Chacha Nehru Bal Chikitsalaya, Geeta Colony, New Delhi, India
| | - Karnika Saigal Kalra
- Department of Microbiology, 75299Chacha Nehru Bal Chikitsalaya, Geeta Colony, New Delhi, India
| | - Diganta Saikia
- Department of Pediatrics, 75299Chacha Nehru Bal Chikitsalaya, Geeta Colony, New Delhi, India
| | - Varshanjali Yadav
- Department of Pediatrics, 75299Chacha Nehru Bal Chikitsalaya, Geeta Colony, New Delhi, India
| | - Juhi Chouksey
- Department of Pediatrics, 75299Chacha Nehru Bal Chikitsalaya, Geeta Colony, New Delhi, India
| | - Mamta Jajoo
- Department of Pediatrics, 75299Chacha Nehru Bal Chikitsalaya, Geeta Colony, New Delhi, India
| | - B L Sherwal
- Director, Chacha Nehru Bal Chikitsalaya, Geeta Colony, New Delhi, India
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Octavius GS, Tan R, Pratama TA, Budiputri CL, Meliani F, Heriyanto RS, Muljadi R, Juliansen A. Cardiac manifestations and diagnostic imaging in pediatric inflammatory multisystem syndrome temporally associated with COVID-19: a systematic review. MEDICAL JOURNAL OF INDONESIA 2022; 31:20-37. [DOI: 10.13181/mji.oa.225754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 01/25/2022] [Indexed: 10/18/2022] Open
Abstract
BACKGROUND Several studies have reported pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) cases with their cardiac manifestations, but only few studies synthesize the cardiovascular characteristics in children with PIMS-TS. However, detecting cardiac abnormalities is crucial in improving patients' outcomes and reducing mortality. This review aimed to summarize the overall symptoms, laboratory, and workup findings in PIMS-TS patients, focusing on cardiovascular manifestations.
METHODS We searched 4 medical databases (PubMed, Science Direct, Medline, and Scielo) and 4 preprint databases (Medrxiv, Research Square, SSRN, and Biorxiv). The literature search was done on November 8, 2021. All case reports, case series, cross-sectional studies, cohort studies, and possible clinical trials published from December 2020 onward that studied PIMS-TS on cardiac manifestation (aged 0–18 years) were included. Studies on multisystem inflammatory syndrome in children, animal studies, and studies without full-text availability were excluded. This review was registered in PROSPERO (CRD42021194468).
RESULTS 59 studies were included with a total of 698 patients. The most common cardiovascular findings were the presence of cardiogenic shock (37%) and hypotension (8.5%). Almost all laboratory values were deranged. Cardiac computed tomography scan mostly showed normal results (56%), followed by cardiomegaly with pericardial effusion (14%). Electrocardiography showed normal findings (46%), ST-segment abnormalities (32%), and abnormal T wave (12%). Echocardiography findings showed left ventricle dysfunction (40.6%), which can be considered most significant, followed by pericardial effusion together with pericarditis (11.4%) and tricuspid regurgitation (6.9%).
CONCLUSIONS This review found various cardiac abnormalities that may develop during PIMS-TS. Due to these findings, we should be more vigilant and not underestimate the consequences in pediatric COVID-19 patients.
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Rouva G, Vergadi E, Galanakis E. Acute abdomen in multisystem inflammatory syndrome in children: A systematic review. Acta Paediatr 2022; 111:467-472. [PMID: 34751972 DOI: 10.1111/apa.16178] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/24/2021] [Accepted: 11/08/2021] [Indexed: 12/22/2022]
Abstract
AIM Multisystem inflammatory syndrome in children (MIS-C), a rare severe complication of SARS-CoV-2 infection, has been recently reported to mimic acute abdomen and lead to surgical interventions, posing challenges for clinicians. In this systematic review, we evaluated the rate of acute abdomen and abdominal surgical emergencies in children with MIS-C. METHODS Systematic review of all MIS-C cases presented with acute abdomen. RESULTS A total of 385 patients with MIS-C, from 38 studies, were included. Gastrointestinal manifestations were prominent in 233/385 (60.5%) children. Acute abdomen was noted in 72/385 (18.7%) of MIS-C cases and in 72/233 (30.9%) of MIS-C cases with gastrointestinal symptoms. Final diagnoses were mostly non-surgical (55/72, 76.4%), such as mesenteric lymphadenitis (23/72, 31.9%), terminal ileitis/ileocolitis (19/72, 26.4%), free abdominal fluid/ascites (8/72, 11.1%) and paralytic ileus (3/72, 4.2%). Laparotomy was performed in 35/72 (48.6%) of children with MIS-C, and acute abdomen and was proven unnecessary in 18/35 (51.4%) cases. True abdominal surgical emergencies, such as appendicitis and obstructive ileus, were confirmed in 17/72 (23.6%) cases. CONCLUSION MIS-C often presents with acute abdomen, mostly due to non-surgical intestinal inflammatory pathology. However, surgical complications occur in patients with MIS-C; therefore, a high index of suspicion should remain.
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Affiliation(s)
- Glykeria Rouva
- Department of Paediatrics University General Hospital of Heraklion Heraklion Greece
| | - Eleni Vergadi
- Department of Paediatrics University General Hospital of Heraklion Heraklion Greece
- Department of Μother and Child, School of Medicine University of Crete Heraklion Greece
| | - Emmanouil Galanakis
- Department of Paediatrics University General Hospital of Heraklion Heraklion Greece
- Department of Μother and Child, School of Medicine University of Crete Heraklion Greece
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Borel M, Xie L, Kapera O, Mihalcea A, Kahn J, Messiah SE. Long-term physical, mental and social health effects of COVID-19 in the pediatric population: a scoping review. World J Pediatr 2022; 18:149-159. [PMID: 35118594 PMCID: PMC8812346 DOI: 10.1007/s12519-022-00515-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 12/26/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND The majority of coronavirus disease 2019 (COVID-19) symptom presentations in adults and children appear to run their course within a couple of weeks. However, a subgroup of adults has started to emerge with effects lasting several months or more after initial infection, which raises questions about the long-term physical, mental and social health effects of COVID-19 in the pediatric population. The purpose of this review was to determine these impacts well into the second year of the pandemic. METHODS A search was conducted using PubMed, Web of Science, Science Direct, and Cochrane between 11/1/2019 and 9/1/2021. Search inclusion criteria were as follows: (1) COVID-19 illness and symptoms in children; (2) severe acute respiratory syndrome coronavirus 2 in children; (3) English language; and (4) human studies only. RESULTS The few studies that have documented long-term physical symptoms in children show that fatigue, difficulty in concentrating (brain fog), sleep disturbances, and sensory problems are the most reported outcomes. Most studies examining the impact of COVID-19 in pediatric populations have focused on initial clinical presentation, and symptoms, which are similar to those in adult populations. In addition, COVID-19 has had a moderate impact on children and adolescents' social environment, which may exacerbate current and future physiological, psychological, behavioral, and academic outcomes. CONCLUSIONS There are limited studies reporting long physical symptoms of COVID-19 in the pediatric population. However, pediatric COVID-19 cases are underreported due to low rates of testing and symptomatic infection, which calls for more longitudinal studies. Children who have experienced COVID-19 illness should be monitored for long physiological, psychological, behavioral, and academic outcomes.
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Affiliation(s)
- Madeline Borel
- School of Public Health, University of Texas Health Science Center, Dallas Campus, 2777 N Stemmons Fwy, Dallas, TX, 75207, USA
- Center for Pediatric Population Health, University of Texas Health School of Public Health and Children's Health System of Texas, Dallas, TX, USA
| | - Luyu Xie
- School of Public Health, University of Texas Health Science Center, Dallas Campus, 2777 N Stemmons Fwy, Dallas, TX, 75207, USA
- Center for Pediatric Population Health, University of Texas Health School of Public Health and Children's Health System of Texas, Dallas, TX, USA
| | - Olivia Kapera
- Center for Pediatric Population Health, University of Texas Health School of Public Health and Children's Health System of Texas, Dallas, TX, USA
- School of Public Health, University of Texas Health Science Center, Austin Campus, Austin, TX, USA
| | - Adrian Mihalcea
- Center for Pediatric Population Health, University of Texas Health School of Public Health and Children's Health System of Texas, Dallas, TX, USA
- School of Public Health, University of Texas Health Science Center, Houston Campus, Houston, TX, USA
| | - Jeffrey Kahn
- Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Children's Health System of Texas, Dallas, TX, USA
| | - Sarah E Messiah
- School of Public Health, University of Texas Health Science Center, Dallas Campus, 2777 N Stemmons Fwy, Dallas, TX, 75207, USA.
- Center for Pediatric Population Health, University of Texas Health School of Public Health and Children's Health System of Texas, Dallas, TX, USA.
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Sharma AG, Kumar V, Sodani R, Sapre A, Singh P, Saha A, Sharma S, Ray S, Pemde H. Predictors of mortality in children admitted with SARS-CoV-2 infection to a tertiary care hospital in North India. J Paediatr Child Health 2022; 58:432-439. [PMID: 34546612 PMCID: PMC8661990 DOI: 10.1111/jpc.15737] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 08/04/2021] [Accepted: 08/23/2021] [Indexed: 12/15/2022]
Abstract
AIM To compare the demographic, clinical, laboratory and radiological parameters of patients with different clinical outcomes (death or discharge) and analyse them to find out the potential predictors for mortality in children hospitalised with SARS-CoV-2 infection. METHODS Retrospective chart review of all patients less than 18 years of age with laboratory-confirmed SARS-CoV-2 infection and requiring hospital admission between 16 April 2020 and 31 October 2020. RESULTS Of 255 children with SARS-CoV-2 infection, 100 patients (median age 62.5 months, 59% males, 70% with moderate to severe disease) were hospitalised, of whom 27 died (median age 72 months, 59% males and 30% severely underweight). The subgroup with comorbidities (n = 14) was older (median age 126 months) and had longer duration of stay (median 10 days). Fever and respiratory symptoms were comparable while gastrointestinal symptoms were more common among non-survivors. Hypoxia at admission (odds ratio (OR) 5.48, P = 0.001), multiorgan dysfunction (OR 75.42, P = 0.001), presence of acute kidney injury (OR 11.66, P = 0.001), thrombocytopenia (OR 4.40, P = 0.003) and raised serum C-reactive protein (CRP) (OR 4.69, P = 0.02) were independently associated with mortality. The median time from hospitalisation to death was 3 days. The deceased group had significantly higher median levels of inflammatory parameters and a higher incidence of complications (myocarditis, encephalitis, acute respiratory distress syndrome and shock). CONCLUSIONS Hypoxia at admission, involvement of three or more organ systems, presence of acute kidney injury, thrombocytopenia and raised serum C-reactive protein were found to be independently associated with increased odds of in-hospital mortality in children admitted with SARS-CoV-2 infection.
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Affiliation(s)
- Ankita G Sharma
- Department of PediatricsLady Hardinge Medical college and Kalawati Saran Children HospitalDelhiIndia
| | - Virendra Kumar
- Department of PediatricsLady Hardinge Medical college and Kalawati Saran Children HospitalDelhiIndia
| | - Ravitanaya Sodani
- Department of PediatricsLady Hardinge Medical college and Kalawati Saran Children HospitalDelhiIndia
| | - Anuja Sapre
- Department of PediatricsLady Hardinge Medical college and Kalawati Saran Children HospitalDelhiIndia
| | - Preeti Singh
- Department of PediatricsLady Hardinge Medical college and Kalawati Saran Children HospitalDelhiIndia
| | - Abhijeet Saha
- Department of PediatricsLady Hardinge Medical college and Kalawati Saran Children HospitalDelhiIndia
| | - Suvasini Sharma
- Department of PediatricsLady Hardinge Medical college and Kalawati Saran Children HospitalDelhiIndia
| | - Sandip Ray
- Department of PediatricsLady Hardinge Medical college and Kalawati Saran Children HospitalDelhiIndia
| | - Harish Pemde
- Department of PediatricsLady Hardinge Medical college and Kalawati Saran Children HospitalDelhiIndia
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Sen S, Samanta M, Biswas A, Sinhamahapatra TK. Orofacial dyskinesia with choreoathetoid movements caused by brainstem encephalitis: A rare complication of SARS-CoV-2-related multisystem inflammatory syndrome in children. J Paediatr Child Health 2022; 58:1680-1684. [PMID: 35148008 PMCID: PMC9115151 DOI: 10.1111/jpc.15902] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 01/03/2022] [Accepted: 01/04/2022] [Indexed: 01/10/2023]
Affiliation(s)
- Sandipan Sen
- Department of PediatricsNilratan Sircar Medical College and HospitalKolkataIndia
| | - Moumita Samanta
- Department of PediatricsNilratan Sircar Medical College and HospitalKolkataIndia
| | - Arnab Biswas
- Department of PediatricsNilratan Sircar Medical College and HospitalKolkataIndia
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Mondal R, Sen B, Sarkar M, Raychaudhuri D, Pal P, Roychowdhoury S, Chattopadhyay A, Hazra A. Clinical profile and outcome of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 series in Eastern India. MEDICAL JOURNAL OF DR. D.Y. PATIL VIDYAPEETH 2022. [DOI: 10.4103/mjdrdypu.mjdrdypu_15_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Clinical Profile of COVID-19 Illness in Children-Experience from a Tertiary Care Hospital. Indian J Pediatr 2022; 89:45-51. [PMID: 34313946 PMCID: PMC8313877 DOI: 10.1007/s12098-021-03822-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Accepted: 05/24/2021] [Indexed: 01/07/2023]
Abstract
OBJECTIVE To detail clinical profile and outcome in children infected with SARS-CoV-2. METHODS This retrospective study was undertaken at a tertiary care pediatric teaching hospital in Northern India. The data on clinical characteristics and outcome of children (< 18 y) with COVID-19 illness from April 2020-October 2020 were reviewed and analyzed. RESULTS A total of 2919 children with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) illness were tested for novel COVID-19 virus in the flu emergency (n = 1744), severe acute respiratory infection (SARI) ward (n = 825), and non-COVID area (n = 350) of the hospital. 8.73% (255/2919) children tested positive for SARS-CoV-2 infection. Of the 255 positive cases, 144 (56.47%) were managed on an outpatient basis and 100 (59 boys) required admission in COVID ward. The mortality rate of patients with SARS-CoV-2 was 11.4% (29/255). Majority of children admitted with COVID-19 had severe to critical illness due to the presence of malnutrition and underlying comorbidities. CONCLUSIONS Children of all age groups were susceptible to COVID-19 illness with a slight male preponderance. Amongst infected, two-third were asymptomatic or had mild symptoms that required outpatient management and home isolation. The adverse outcomes were more commonly seen in infants and children > 10 y of age with malnutrition and comorbid illness.
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Mehra B, Pandey M, Gupta D, Oberoi T, Jerath N, Sharma R, Lal N, Singha C, Malhotra B, Manocha V, Simalti AK, Arya Y, Dugaya SK, Kalra S, Chitkara AJ, Sachdev A, Gupta N. COVID-19-associated Multisystem Inflammatory Syndrome in Children: A Multicentric Retrospective Cohort Study. Indian J Crit Care Med 2021; 25:1176-1182. [PMID: 34916752 PMCID: PMC8645810 DOI: 10.5005/jp-journals-10071-23996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Background Multisystem inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new entity affecting a small percentage of children during the COVID-19 pandemic. Materials and methods Demography, clinical, and laboratory variables of children admitted from April to September 2020 with MIS-C were studied retrospectively at eight hospitals in Delhi, India. Results We identified 120 patients [median age: 7 years (interquartile range (IQR): 4–10)] with male-to-female ratio of 2.3:1. Overall, 73 out of 120 children (60.8%) presented with shock, 63 (52.5%) required inopressor support, and 51 (43%) required respiratory support. We categorized the cohort into three observed clinical phenotypes: MIS-C with shock (n = 63), MIS-C with Kawasaki disease (KD) (n = 23), and MIS-C without shock and KD (n = 34). Atypical presentations were hypothermia, orchitis, meningoencephalitis, demyelination, polyneuropathy, pancreatitis, and appendicitis. Ninety-four percent had laboratory evidence of SARS-CoV-2 (78.3%, seropositive and 15.8%, RT-PCR positive). The median C-reactive protein (CRP) was 136 mg/L (IQR, 63.5–212.5) and ferritin was 543 ng/mL (IQR, 225–1,127). More than 90% received immunomodulatory therapy (intravenous immunoglobulins and/or steroids) with an excellent outcome (96% survived). CRP and absolute neutrophil count (ANC) were correlated statistically with severity. Conclusion MIS-C data from Delhi are presented. Rising CRP and ANC predict the severe MIS-C. How to cite this article Mehra B, Pandey M, Gupta D, Oberoi T, Jerath N, Sharma R, et al. COVID-19-associated Multisystem Inflammatory Syndrome in Children: A Multicentric Retrospective Cohort Study. Indian J Crit Care Med 2021;25(10):1176–1182.
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Affiliation(s)
- Bharat Mehra
- Department of Pediatric Intensive Care, Max Super Speciality Hospital, New Delhi, India
| | - Mukul Pandey
- Department of Pediatrics, St Stephens Hospital, New Delhi, India
| | - Dhiren Gupta
- Department of Pediatric Intensive Care, Sir Ganga Ram Hospital, New Delhi, India
| | - Tania Oberoi
- Department of PICU, Apollo Hospital, New Delhi, India
| | - Nameet Jerath
- Department of PICU, Apollo Hospital, New Delhi, India
| | - Rachna Sharma
- Department of Pediatric Critical Care, BLK Super Speciality Hospital, New Delhi, India
| | - Naresh Lal
- Department of Pediatric Critical Care, BLK Super Speciality Hospital, New Delhi, India
| | | | - Bhavana Malhotra
- Department of Pediatric Intensive Care, Sir Ganga Ram Hospital, New Delhi, India
| | - Vinamra Manocha
- Department of Pediatrics, Mata Chanan Devi Hospital, New Delhi, India
| | - Ashish K Simalti
- Department of Pediatric Critical Care, Military Hospital, Dehradun, Uttarakhand, India
| | - Yogesh Arya
- Department of PICU, Madhukar Rainbow Children's Hospital, New Delhi, India
| | - Sandeep K Dugaya
- Department of Pediatrics, Max Super Speciality Hospital, New Delhi, India
| | - Swati Kalra
- Department of Pediatrics, Baba Saheb Ambedkar Hospital, New Delhi, India
| | - Amar J Chitkara
- Department of Pediatrics, Max Super Speciality Hospital, New Delhi, India
| | - Anil Sachdev
- Department of Pediatric Intensive Care, Sir Ganga Ram Hospital, New Delhi, India
| | - Neeraj Gupta
- Department of Pediatric Intensive Care, Sir Ganga Ram Hospital, New Delhi, India
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Solanki R, Gupta A, Roy S, Pal S, Khan MF. The " After Wave": Pediatric multisystem inflammatory syndrome temporally associated with COVID-19 in a series of children from Eastern India. Med J Armed Forces India 2021; 78:S133-S138. [PMID: 34931107 PMCID: PMC8674121 DOI: 10.1016/j.mjafi.2021.10.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 10/19/2021] [Indexed: 11/30/2022] Open
Abstract
Background The objective of the study is to describe the presentation, treatment and outcomes of children with multisystem inflammatory syndrome with COVID-19 (MIS-C) in a tertiary care centre in Eastern India. Methods Retrospective data of children diagnosed with MIS-C during the SARS CoV-2 pandemic were obtained from hospital records. Clinical details, laboratory profile, treatment protocol and outcomes of children with MIS-C between 01 Nov 2020 and 30 June 2021 were analysed. Results Ten children (7 males) with a mean age of 6.8 years (median age 5.5 years, interquartile range 3.75-9.5) were analysed. COVID-19 RT-PCR was negative in all patients, whereas the IgG COVID antibody was positive in all children (100%). Seven children (7/10) had a history of contact with SARS CoV-2–positive adults. Five (5/10) children presented with cardiogenic shock. All children had evidence of a hyperinflammatory syndrome. Nine children (9/10) had predominant gastrointestinal and cardiovascular involvement. None had echocardiographic evidence of coronary dilatation or aneurysms either on admission or on follow-up. The elevated neutrophil lymphocyte ratio and D-dimer were found in all patients. All children responded to immunomodulatory treatment. None had residual deficit on discharge or at 4-week follow-up. There was no mortality. Conclusion Children with MIS-C have good prognosis if early immunomodulatory treatment is instituted. Further prospective studies for long-term outcomes in children with MIS-C are required it being a novel entity recently described.
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Affiliation(s)
- Reema Solanki
- Classified Specialist (Pediatrics), Command Hospital (Eastern Command), Kolkata, India
| | - Aparajita Gupta
- Classified Specialist (Pediatrics) & Pediatric Neurologist, Command Hospital (Eastern Command), Kolkata, India
| | - Shuvendu Roy
- Senior Advisor & Head (Pediatrics), Command Hospital (Eastern Command), Kolkata, India
| | - Sunandan Pal
- Resident (Paediatrics), Command Hospital (Eastern Command), Kolkata, India
| | - Mohd Faisal Khan
- Specialist Medical Officer, 181 Military Hospital, C/o 99 APO, India
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40
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Guimarães D, Pissarra R, Reis-Melo A, Guimarães H. Multisystem inflammatory syndrome in children (MISC): A systematic review. Int J Clin Pract 2021; 75:e14450. [PMID: 34105843 DOI: 10.1111/ijcp.14450] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 06/02/2021] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE The aim of this systematic review was to analyse current literature and reported cases of multisystem inflammatory syndrome in children (MISC), concerning its clinical spectrum, complications associated, therapeutic strategies and distinguishing features of other clinical syndromes. METHODS Extensive literature research was performed in MEDLINE (through PubMed), Scopus and Web of Science from December 2019 to December 2020. First analysis included all article titles and abstracts screening to identify relevant studies, and second analysis included a full-text screening of previously selected studies. Eligibility was assessed independently by two authors, and disagreements were resolved by discussion and consensus. Data were extracted on MISC definition, demographic data, clinical features, diagnostic tests, laboratory analysis and imaging, therapeutical approach and outcomes. RESULTS Common symptoms included gastrointestinal (70%), rash (57%) and cardiovascular (52% with shock). Notable differences with Kawasaki disease were identified including age, clinical presentation and cardiac involvement. Thirty per cent presented positive severe acute respiratory syndrome coronavirus-2 reverse transcription polymerase chain reaction and 51% positive serologies. Sixty-two per cent received intravenous immunoglobulin and 42% glucocorticoids. Sixty-two per cent required intensive care and 21 children died (<2%). Severe presentations were associated with neurological symptoms, hepatitis and acute kidney injury. CONCLUSIONS MISC raises concern on its severe cardiac involvement at presentation, with frequent intensive care and immunomodulatory therapy need. Short-term outcomes seem to be favourable, with cardiac dysfunction recovery and low mortality rates.
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Affiliation(s)
| | - Rita Pissarra
- Pediatrics Department, Centro Hospitalar Universitário São João, Porto, Portugal
| | - Ana Reis-Melo
- Faculty of Medicine, University of Porto, Porto, Portugal
- Pediatric Infectious Diseases and Primary Immunodeficiencies Unit, Centro Hospitalar Universitário de São João, Porto, Portugal
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Patnaik S, Jain MK, Ahmed S, Dash AK, P RK, Sahoo B, Mishra R, Behera MR. Short-term outcomes in children recovered from multisystem inflammatory syndrome associated with SARS-CoV-2 infection. Rheumatol Int 2021; 41:1957-1962. [PMID: 34259880 PMCID: PMC8278175 DOI: 10.1007/s00296-021-04932-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 06/19/2021] [Indexed: 12/14/2022]
Abstract
Multi-system inflammatory syndrome in children (MIS-C) associated with COVID-19 is a recently recognised potentially life-threatening entity. There is limited data on post-MIS-C sequelae. 21 children fulfilling the WHO criteria for MIS-C were included in our study. Data were collected at baseline and at 12-16 weeks post-discharge to look for any persistent sequelae mainly relating to the lungs or heart including coronary arteries. Fever was the most common presentation, found in 18 (85.7%) patients. All had a marked hyper-inflammatory state. Low ejection fraction (EF) was found in 10 (47.6%), but none had any coronary artery abnormality. All received corticosteroids, while 7 (33.3%) children required additional treatment with intravenous Immunoglobulins. 20 children improved while 1 left against medical advice. At discharge, 3 children had impaired left ventricular function. At median 15 weeks' follow-up, no persistent complications were found. EF had returned to normal and no coronary artery abnormalities were found during repeat echocardiography. Chest radiographs showed no fibrosis and all biochemical parameters had normalized. The children with MIS-C are extremely sick during the acute stage. Timely and adequate management led to full recovery without any sequelae at a median follow-up of 15 weeks.
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Affiliation(s)
- Sibabratta Patnaik
- Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Mukesh Kumar Jain
- Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Sakir Ahmed
- Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Arun Kumar Dash
- Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Ram Kumar P
- Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Bandya Sahoo
- Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Reshmi Mishra
- Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Manas Ranjan Behera
- Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, India
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Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison. Nat Rev Rheumatol 2021; 17:731-748. [PMID: 34716418 PMCID: PMC8554518 DOI: 10.1038/s41584-021-00709-9] [Citation(s) in RCA: 152] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/04/2021] [Indexed: 12/12/2022]
Abstract
Children and adolescents infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are predominantly asymptomatic or have mild symptoms compared with the more severe coronavirus disease 2019 (COVID-19) described in adults. However, SARS-CoV-2 is also associated with a widely reported but poorly understood paediatric systemic vasculitis. This multisystem inflammatory syndrome in children (MIS-C) has features that overlap with myocarditis, toxic-shock syndrome and Kawasaki disease. Current evidence indicates that MIS-C is the result of an exaggerated innate and adaptive immune response, characterized by a cytokine storm, and that it is triggered by prior SARS-CoV-2 exposure. Epidemiological, clinical and immunological differences classify MIS-C as being distinct from Kawasaki disease. Differences include the age range, and the geographical and ethnic distribution of patients. MIS-C is associated with prominent gastrointestinal and cardiovascular system involvement, admission to intensive care unit, neutrophilia, lymphopenia, high levels of IFNγ and low counts of naive CD4+ T cells, with a high proportion of activated memory T cells. Further investigation of MIS-C will continue to enhance our understanding of similar conditions associated with a cytokine storm.
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Krishna MR, Sennaiyan UN. Peak left atrial longitudinal strain: A potential diagnostic entity in children with multi-inflammatory syndrome in children. Ann Pediatr Cardiol 2021; 14:393-396. [PMID: 34667414 PMCID: PMC8457272 DOI: 10.4103/apc.apc_18_21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 02/14/2021] [Accepted: 03/01/2021] [Indexed: 12/19/2022] Open
Abstract
The multi-inflammatory syndrome in children is a poorly understood febrile illness potentially linked to an immune response to COVID-19 infection. The disease is characterized by fever and elevated acute-phase reactants. A number of children with clinical and laboratory evidence of cardiovascular involvement have normal echocardiograms by conventional assessment. The peak left atrial longitudinal strain obtained by atrial deformation analysis could potentially be diagnostic of this condition in children who do not have abnormalities identified on conventional assessment.
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Affiliation(s)
- Mani Ram Krishna
- Department of Pediatric Cardiology, R.K. Hospital for Women and Children, Thanjavur, Tamil Nadu, India
| | - Usha Nandhini Sennaiyan
- Department of Pediatric Cardiology, R.K. Hospital for Women and Children, Thanjavur, Tamil Nadu, India
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Bagri NK, Deepak RK, Meena S, Gupta SK, Prakash S, Setlur K, Satapathy J, Chopra K, Upadhyay AD, Ramakrishnan S, Lodha R, Dar L, Trikha A, Kabra SK. Outcomes of multisystem inflammatory syndrome in children temporally related to COVID-19: a longitudinal study. Rheumatol Int 2021; 42:477-484. [PMID: 34665296 PMCID: PMC8524205 DOI: 10.1007/s00296-021-05030-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 10/11/2021] [Indexed: 12/14/2022]
Abstract
To study the clinical, laboratory characteristics and outcomes of multisystem inflammatory syndrome in children (MIS-C) temporally related to coronavirus disease 2019 (COVID-19) in a resource-limited setting. All children meeting the World Health Organization case definition of MIS-C were prospectively enrolled. Baseline clinical and laboratory parameters were compared between survivors and non-survivors. Enrolled subjects were followed up for 4-6 weeks for evaluation of cardiac outcomes using echocardiography. The statistical data were analyzed using the stata-12 software. Thirty-one children with MIS-C were enrolled in an 11-month period. Twelve children had preexisting chronic systemic comorbidity. Fever was a universal finding; gastrointestinal and respiratory manifestations were noted in 70.9% and 64.3%, respectively, while 57.1% had a skin rash. Fifty-eight percent of children presented with shock, and 22.5% required mechanical ventilation. HSP like rash, gangrene and arthritis were uncommon clinical observations.The median duration of hospital stay was 9 (6.5-18.5) days: four children with preexisting comorbidities succumbed to the illness. The serum ferritin levels (ng/ml) [median (IQR)] were significantly higher in non-survivors as compared to survivors [1061 (581, 2750) vs 309.5 (140, 720.08), p value = 0.045]. Six patients had coronary artery involvement; five recovered during follow-up, while one was still admitted. Twenty-six children received immunomodulatory drugs, and five improved without immunomodulation. The choice of immunomodulation (steroids or intravenous immunoglobulin) did not affect the outcome. Most children with MIS-C present with acute hemodynamic and respiratory symptoms.The outcome is favorable in children without preexisting comorbidities.Raised ferritin level may be a poor prognostic marker. The coronary outcomes at follow-up were reassuring.
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Affiliation(s)
- Narendra Kumar Bagri
- Division of Pediatric Rheumatology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
| | - Rakesh Kumar Deepak
- Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India
| | - Suneeta Meena
- Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kumar Gupta
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Satya Prakash
- All India Institute of Medical Sciences, New Delhi, India
| | - Kritika Setlur
- All India Institute of Medical Sciences, New Delhi, India
| | | | - Karan Chopra
- All India Institute of Medical Sciences, New Delhi, India
| | - Ashish Datt Upadhyay
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | | | - Rakesh Lodha
- All India Institute of Medical Sciences, New Delhi, India
| | - Lalit Dar
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India
| | - Anjan Trikha
- Department of Anesthesiology and Critical Care, All India Institute of Medical Sciences, New Delhi, India
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Sözeri B, Çağlayan Ş, Atasayan V, Ulu K, Coşkuner T, Pelin Akbay Ö, Hasbal Akkuş C, Atay G, Salı E, Karacan M, Öner T, Erdoğan S, Demir F. The clinical course and short-term health outcomes of multisystem inflammatory syndrome in children in the single pediatric rheumatology center. Postgrad Med 2021; 133:994-1000. [PMID: 34605352 PMCID: PMC8544667 DOI: 10.1080/00325481.2021.1987732] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Objectives Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe condition resulting in excessive response of the immune system after SARS-CoV-2 infection. We report a single-center cohort of children with MIS-C, describing the spectrum of presentation, therapies, clinical course, and short-term outcomes. Methods This is a prospective observational study from to a tertiary pediatric rheumatology center including patients (aged 1 month to 21 years) diagnosed with MIS-C between April 2020-April 2021. Demographic, clinical, laboratory results and follow-up data were collected through the electronic patient record system and analyzed. Results A total of 67 patients with MIS-C were included in the study. Fever was detected in all patients; gastrointestinal system symptoms were found in 67.2% of the patients, rash in 38.8%, conjunctivitis in 31.3%, hypotension in 26.9% myocarditis, and/or pericarditis in 22.4%, respectively. Respiratory symptoms were only in five patients (7.5%). Kawasaki Disease like presentation was found 37.3% of the patients. The mean duration of hospitalization was 11.8 7.07 days. Fifty-seven patients (85%) received intravenous immunoglobulin (IVIG), 45 (67%) received corticosteroids, 17 (25.3%) received anakinra, and one (1.5%) received tocilizumab. Seven of the patients (10.4%) underwent therapeutic plasma exchange (TPE). In 21 (31.3%) patients, a pediatric intensive care unit (PICU) was required in a median of 2 days. The first finding to improve was fever, while the first parameter to decrease was ferritin (median 6.5 days (IQR, 4–11.2 days)). Sixty-five patients were discharged home with a median duration of hospital stay of 10 days (IQR, 7–15 days). Conclusion Patients with MIS-C may have severe cardiac findings and intensive care requirements in admission and hospital follow-up. The vast majority of these findings improve with effective treatment without any sequelae until discharge and in a short time in follow-up. Although the pathogenesis and treatment plan of the disease are partially elucidated, follow-up studies are needed in terms of long-term prognosis and relapse probabilities.
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Affiliation(s)
- Betül Sözeri
- Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Şengül Çağlayan
- Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Vildan Atasayan
- Department of Pediatric Cardiology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Kadir Ulu
- Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Taner Coşkuner
- Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Özge Pelin Akbay
- Department of Pediatrics, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Canan Hasbal Akkuş
- Department of Pediatrics, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Gürkan Atay
- Department of Pediatric Intensive Care Unit, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Enes Salı
- Department of Pediatric Infectious Disease, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Mehmet Karacan
- Department of Pediatric Cardiology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Taliha Öner
- Department of Pediatric Cardiology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Seher Erdoğan
- Department of Pediatric Intensive Care Unit, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Ferhat Demir
- Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
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Balagurunathan M, Natarajan T, Karthikeyan J, Palanisamy V. Clinical spectrum and short-term outcomes of multisystem inflammatory syndrome in children in a south Indian hospital. Clin Exp Pediatr 2021; 64:531-537. [PMID: 34353002 PMCID: PMC8498016 DOI: 10.3345/cep.2021.00374] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 07/15/2021] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Multisystem inflammatory syndrome in children (MIS-C) is a new hyperinflammatory variant that evolved during the coronavirus disease 2019 pandemic. Although the precise pathophysiology of MIS-C is uncertain, it is thought to be due to immune dysregulation occurring after recovery from acute infection. PURPOSE Our study aimed to analyze the clinical spectrum, laboratory parameters, imaging characteristics, treatment strategies, and short-term outcomes of children with a diagnosis of MIS-C. METHODS This retrospective and prospective observational study included children less than 16 years of age who were admitted to the pediatric unit of a tertiary care teaching hospital in south India between August 2020 to January 2021 with a diagnosis of MIS-C according to World Health Organization criteria. RESULTS Twenty-one children were included in the analysis; all had fever with variable combinations of other symptoms. The mean age was 6.9 years; 71.4% were male. Gastrointestinal (80.9%) and cardiovascular (80.9%) systems were the most commonly affected. The majority of children had elevated inflammatory markers, and 16 (76.2%) had echocardiographic abnormalities mimicking Kawasaki disease. Eleven children (52.4%) required intensive care admission, 3 (14.3%) required supplemental oxygen, and 4 (19%) required inotropes. Nine (42.9%) were treated with intravenous immunoglobulin alone, 6 (28.6%) with steroids alone, and 3 (14.3%) with steroids and immunoglobulin. The median hospital stay was 6 days; there were no fatalities. Overweight/obesity, elevated ferritin, and mucocutaneous involvement were significantly associated with a prolonged hospital stay (≥7 days). Sixteen children (76.2%) were followed up till now and all of them had no clinical concerns. CONCLUSION MIS-C is an emerging disease with variable presentation. A high index of suspicion is necessary for its early identification and appropriate management. Further research is essential for developing optimal treatment strategies.
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Affiliation(s)
| | - Thrilok Natarajan
- Department of Pediatrics, PSG Institute of Medical Sciences and Research, Tamilnadu, India
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Coronavirus Disease 2019-Related Multisystem Inflammatory Syndrome in Children: A Systematic Review and Meta-Analysis. Biochem Res Int 2021; 2021:5596727. [PMID: 34336288 PMCID: PMC8324361 DOI: 10.1155/2021/5596727] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 05/17/2021] [Accepted: 07/10/2021] [Indexed: 01/19/2023] Open
Abstract
Background This study aimed to describe the clinical symptoms, laboratory findings, treatment, and outcomes of coronavirus disease 2019-related multisystem inflammatory syndrome in children to provide a reference for clinical practice. Methods We employed a literature search of databases such as PubMed, Web of Science, EMBASE, and Johns Hopkins University for articles on COVID-19-related multisystem inflammatory syndrome in children published between April 1, 2020, and January 15, 2021. High-quality articles were selected for analysis on the basis of their quality standard scores. Using R3.6.3 software, meta-analyses of random- or fixed-effects models were used to determine the prevalence of comorbidities. Subgroup analysis was also performed to determine heterogeneity. Results A total of 57 articles (2,290 pediatric patients) were included in the study. Clinical Manifestations. :ncidences of fever, gastrointestinal symptoms, respiratory symptoms, and musculoskeletal symptoms (myalgias or arthralgias) were 99.91% (95% CI: 99.67–100%), 82.72% (95% CI: 78.19–86.81%), 53.02% (45.28–60.68%), and 14.16% (95% CI: 8.4–21.12%), respectively. The incidences of rash, conjunctival injection, lymphadenopathy, dry cracked lips, neurologic symptoms (headache, altered mental status, or confusion), swollen hands and feet, typical Kawasaki disease, and atypical Kawasaki disease were 59.34% (95% CI: 54.73–63.87%), 55.23% (95% CI: 50.22–60.19%), 27.07% (95% CI: 19.87–34.93%), 46.37% (95% CI: 39.97–52.83%), 28.87% (95% CI: 22.76–35.40%), 28.75% (95% CI: 21.46–36.64%), 17.32% (95% CI: 15.44–19.29%), and 36.19% (95% CI: 21.90–51.86%), respectively. The incidences of coronary artery dilation, aneurysm, pericardial effusion, myocarditis, myocardial dysfunction, high troponin, and N-terminal pro-B-type natriuretic peptide were 17.83%, 6.85%, 20.97%, 35.97%, 56.32%, 76.34%, and 86.65%, respectively. The incidences of reduced lymphocytes, thrombocytopenia, hypoalbuminemia, elevated C-reactive protein, ferritin, LDH, interleukin-6, PCT, and FIB were 61.51%, 26.42%, 77.92%, 98.5%, 86.79%, 80.59%, 89.30%, 85.10%, and 87.01%, respectively. PICU Hospitalization Rate and Mortality. The incidences of PICU hospitalization or with shock were 72.79% and 55.68%, respectively. The mortality rate was 1.00%. Conclusion and Relevance. PICU hospitalization and shock rates of multisystem inflammatory syndrome in children associated with COVID-19 were high, and its cumulative multiorgans and inflammatory indicators are increased, but if treated in time, the mortality rate was low.
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Angurana SK, Awasthi P, Thakur A, Randhawa MS, Nallasamy K, Kumar MR, Naganur S, Kumar M, Goyal K, Ghosh A, Bansal A, Jayashree M. Intensive Care Needs and Short-Term Outcome of Multisystem Inflammatory Syndrome in Children (MIS-C): Experience from North India. J Trop Pediatr 2021; 67:6309460. [PMID: 34170328 PMCID: PMC8344677 DOI: 10.1093/tropej/fmab055] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVES To describe the intensive care needs and outcome of multisystem inflammatory syndrome in children (MIS-C). METHODOLOGY This retrospective study was conducted in the pediatric emergency, pediatric intensive care unit (PICUs) and the coronavirus disease 2019 (COVID 19) hospital of a tertiary teaching and referral hospital in North India over a period of 5 months (September 2020 to January 2021). Clinical details, laboratory investigations, intensive care needs, treatment and short-term outcome were recorded. RESULTS Forty children with median interquartile range age of 7 (5-10) years were enrolled. The common clinical features were fever (97.5%), mucocutaneous involvement (80%), abdominal (72.5%) and respiratory (50%) symptoms. Shock was noted in 80% children. Most cases (85%) required PICU admission where they received nasal prong oxygen (40%), non-invasive (22.5%) and invasive (22.5%) ventilation and vasoactive drug support (72.5%). The confirmation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) exposure was in the form of positive serology (66.7%), reverse transcriptase polymerase chain reaction (10%), and contact with SARS-CoV-2 positive case (12.5%). The common echocardiographic findings included myocardial dysfunction (ejection fraction <55%; 72.5%), and coronary artery dilatation or aneurysm (22.5%). The immunomodulatory treatment included intravenous immunoglobulin (2 g/kg) (100%) and steroids (methylprednisolone 10-30 mg/kg/day for 3-5 days) (85%). Aspirin was used in 80% and heparin (low molecular weight) in 7.5% cases. Two children died (5%) and median duration of PICU and hospital stay in survivors were 5 (2-8) and 7 (4-9) days, respectively. Children with shock showed higher total leucocyte count and higher rates of myocardial dysfunction. CONCLUSION Cardiovascular involvement and shock are predominant features in severe disease. Early diagnosis can be challenging given the overlapping features with other diagnoses. A high index of suspicion is warranted in children with constellation of fever, mucocutaneous, gastrointestinal and cardiovascular involvement alongwith evidence of systemic inflammation and recent or concurrent SARS-CoV-2 infection. The short-term outcome is good with appropriate organ support therapies and immunomodulation.
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Affiliation(s)
- Suresh Kumar Angurana
- Division of Pediatric Critical Care, Department of Pediatrics, Advanced Pediatrics Centre
| | - Puspraj Awasthi
- Division of Pediatric Critical Care, Department of Pediatrics, Advanced Pediatrics Centre
| | - Ajay Thakur
- Division of Pediatric Critical Care, Department of Pediatrics, Advanced Pediatrics Centre
| | | | - Karthi Nallasamy
- Division of Pediatric Critical Care, Department of Pediatrics, Advanced Pediatrics Centre
| | - Manoj Rohit Kumar
- Department of Cardiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Sanjeev Naganur
- Department of Cardiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Mahendra Kumar
- Department of Immunopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Kapil Goyal
- Department of Virology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Arnab Ghosh
- Department of Virology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Arun Bansal
- Division of Pediatric Critical Care, Department of Pediatrics, Advanced Pediatrics Centre
| | - Muralidharan Jayashree
- Division of Pediatric Critical Care, Department of Pediatrics, Advanced Pediatrics Centre,Corresponding author: Muralidharan Jayashree, Professor and Unit Head, Division of Pediatric Emergency and Intensive Care, Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
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Behera JR, Jain MK, Sahu SK, Patnaik S. Multisystem Inflammatory Syndrome in Children Associated with COVID-19: An Interim Review. J PEDIAT INF DIS-GER 2021. [DOI: 10.1055/s-0041-1729182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
AbstractThe pediatric population is relatively less affected by novel coronavirus disease 2019 (COVID-19) compared with adults, both in numbers and severity. However, evolution of a new entity, named multisystem inflammatory syndrome in children (MIS-C), has led to significant number of children being admitted to hospital, especially to intensive care units. Case definitions of MIS-C have been defined by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) separately. Autoantibodies and antibody-dependent enhancement (ADE) are the key factors proposed in pathogenesis, leading to immune dysregulation, and cytokine storm. Three distinct clinical types are observed as follows: (1) fever and elevated inflammatory markers with no end-organ damage; (2) shock with severe myocardial dysfunction similar to toxic shock syndrome (TSS); and (3) with mucocutaneous features like Kawasaki's disease (KD). Cardiovascular and gastrointestinal symptoms are the predominant presentations. Inflammatory markers like C-reactive protein (CRP), ferritin, and interleukin (IL)-6 are raised along with high D-dimer and lactate dehydrogenase (LDH). Echocardiography may demonstrate low left ventricular ejection fraction (<50%) and/or coronary aneurysms. Reverse-transcription polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is usually negative, with most having antibodies against the virus. KD, KD shock syndrome (KDSS), and toxic shock syndrome (TSS) are the important differential diagnoses to be considered. Immunomodulatory therapy is the cornerstone of the management. Intravenous immunoglobulin (IVIg) is preferred, the next option being steroids. Supportive care, antiplatelet, and anticoagulation medications, when indicated, are also vital aspects of treatment plan. The prognosis is favorable with low mortality but meticulous cardiac monitoring and follow-up by a multidisciplinary team is very important. Being an evolving disease, future research may reveal different manifestations, newer diagnostic modalities, and better treatment options.
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Affiliation(s)
- Jyoti R. Behera
- Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Mukesh K. Jain
- Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Sanjay K. Sahu
- Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
| | - Sibabratta Patnaik
- Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
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Sancho-Shimizu V, Brodin P, Cobat A, Biggs CM, Toubiana J, Lucas CL, Henrickson SE, Belot A, Tangye SG, Milner JD, Levin M, Abel L, Bogunovic D, Casanova JL, Zhang SY. SARS-CoV-2-related MIS-C: A key to the viral and genetic causes of Kawasaki disease? J Exp Med 2021; 218:e20210446. [PMID: 33904890 PMCID: PMC8080850 DOI: 10.1084/jem.20210446] [Citation(s) in RCA: 101] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 03/24/2021] [Accepted: 04/07/2021] [Indexed: 12/15/2022] Open
Abstract
Multisystem inflammatory syndrome in children (MIS-C) emerged in April 2020 in communities with high COVID-19 rates. This new condition is heterogenous but resembles Kawasaki disease (KD), a well-known but poorly understood and clinically heterogenous pediatric inflammatory condition for which weak associations have been found with a myriad of viral illnesses. Epidemiological data clearly indicate that SARS-CoV-2 is the trigger for MIS-C, which typically occurs about 1 mo after infection. These findings support the hypothesis of viral triggers for the various forms of classic KD. We further suggest that rare inborn errors of immunity (IEIs) altering the immune response to SARS-CoV-2 may underlie the pathogenesis of MIS-C in some children. The discovery of monogenic IEIs underlying MIS-C would shed light on its pathogenesis, paving the way for a new genetic approach to classic KD, revisited as a heterogeneous collection of IEIs to viruses.
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Affiliation(s)
- Vanessa Sancho-Shimizu
- Department of Paediatric Infectious Diseases and Virology, Imperial College London, London, UK
- Centre for Paediatrics and Child Health, Faculty of Medicine, Imperial College London, London, UK
| | - Petter Brodin
- Science for Life Laboratory, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
| | - Aurélie Cobat
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France
- University of Paris, Imagine Institute, Paris, France
| | - Catherine M. Biggs
- Department of Pediatrics, University of British Columbia, Vancouver, Canada
- British Columbia Children’s Hospital Research Institute, Vancouver, Canada
| | - Julie Toubiana
- Department of General Pediatrics and Pediatric Infectious Diseases, Necker Hospital for Sick Children, Assistance Publique - Hôpitaux de Paris, University of Paris, Paris, France
- Pasteur Institute, Biodiversity and Epidemiology of Bacterial Pathogens, Paris, France
| | - Carrie L. Lucas
- Department of Immunobiology, Yale University School of Medicine, New Haven, CT
| | - Sarah E. Henrickson
- Division of Allergy Immunology, Children’s Hospital of Philadelphia, Philadelphia, PA
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Alexandre Belot
- Centre International de Recherche en Infectiologie, University of Lyon, Institut National de la Santé et de la Recherche Médicale, U1111, Université Claude Bernard, Lyon 1, Le Centre National de la Recherche Scientifique, UMR5308, Lyon, France
- National Reference Center for Rheumatic, Autoimmune and Systemic Diseases in Children (RAISE), Pediatric Nephrology, Rheumatology, Dermatology Unit, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon, France
| | - Stuart G. Tangye
- Garvan Institute of Medical Research, Darlinghurst, Australia
- St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales Sydney, Sydney, Australia
| | - Joshua D. Milner
- Department of Pediatrics, Columbia University Irving Medical Center, New York, NY
| | - Michael Levin
- Department of Paediatric Infectious Diseases and Virology, Imperial College London, London, UK
- Centre for Paediatrics and Child Health, Faculty of Medicine, Imperial College London, London, UK
| | - Laurent Abel
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France
- University of Paris, Imagine Institute, Paris, France
| | - Dusan Bogunovic
- Center for Inborn Errors of Immunity, Precision Immunology Institute, Mindich Child Health and Development Institute, Department of Microbiology, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Jean-Laurent Casanova
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France
- University of Paris, Imagine Institute, Paris, France
- Howard Hughes Medical Institute, New York, NY
| | - Shen-Ying Zhang
- St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY
- Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France
- University of Paris, Imagine Institute, Paris, France
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