COVID-19 and Multisystem Inflammatory Syndrome in Latin American children: a multinational study

Background To date, there are no comprehensive data on pediatric COVID19 from Latin America. This study aims to assess COVID-19 and Multisystem Inflammatory Syndrome (MIS C) in Latin American children, in order to appropriately plan and allocate resources to face the pandemic on a local and International lever Methods Ambispective multicentre cohort study from five Latin American countries. Children aged 18 years or younger with microbiologically confirmed SARS CoV 2 infection were included. Findings 409 children were included, with a median age of 53.0 years (IQR 0.6 9.0). Of these, 95 191 (23.2%) were diagnosed with MIS C. 191 (46.7%) children were admitted to hospital and 52 (12.7%) required admission to a Pediatric Intensive Care Unite (PICU). 92 (22.5%) patients required oxygen support: 8 (2%) were started on continuous positive airway pressure (CPAP) and 29 (7%) on mechanical ventilation. 35 (8.5%) patients required inotropic support. The following factors were associated with PICU admission: pre-existing medical condition (P < 0.0001), immunodeficiency (P = 0.01), lower respiratory tract infection (P< 0.0001), gastrointestinal symptoms (P = 0.006), radiological changes suggestive of pneumonia and acute respiratory distress syndrome (P< 0.0001), low socioeconomic conditions (P 0.009). Conclusions This study shows a generally more severe form of COVID 19 and a high number of MIS C in Latin American children, compared with studies from China, Europe and North America, and support current evidence of a more severe disease in Latin/Hyspanic children or in people of lower socioeconomic level. The findings highlight an urgent need of more data of COVID 19 in South America.

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CLINICAL AND LABORATORY CHARACTERISTICS OF SARS-COV-2 INFECTION IN CHILDREN AND ADOLESCENTS

Revista Paulista de Pediatria ◽

10.1590/1984-0462/2021/39/2020231 ◽

2021 ◽

Vol 39 ◽

Author(s):

Marlos Melo Martins ◽

Arnaldo Prata-Barbosa ◽

Maria Clara de Magalhães-Barbosa ◽

Antonio José Ledo Alves da Cunha

Keyword(s):

Latin American ◽

Inflammatory Responses ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Current Evidence ◽

Cochrane Library ◽

Childhood And Adolescence ◽

Inflammatory Reactions ◽

One Year ◽

Novel Coronavirus

ABSTRACT Objective: To present the current evidence on clinical and laboratory characteristics of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during childhood and adolescence. Data source: This is a narrative review conducted in the databases: Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Latin American and Caribbean Health Sciences Literature in the Virtual Health Library (LILACS/VHL), Scopus, Web of Science, Cochrane Library, portal of the Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES), Scientific Electronic Library Online (SciELO), ScienceDirect, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The terms used were SARS-CoV-2, COVID-19, novel coronavirus, child, newborn, and adolescent. Data synthesis: Unlike adults, most children infected by SARS-CoV-2 have mild or asymptomatic clinical presentations. Symptomatic children mainly have low fever and cough, with some associated gastrointestinal symptoms. Severe cases are rare and occur especially in infants under one year of age. Detection of viral particles in feces seems to be more persistent in children and can be used as a tool for diagnosis and control of the quarantine period. Different from adults, children can present distinct inflammatory responses, as has happened in new cases of Kawasaki-like syndrome associated with SARS-CoV-2 infection. Conclusions: Most children have asymptomatic or mild presentations, with a prevalence of fever, cough, and gastrointestinal symptoms. New cases with different systemic inflammatory reactions in children have been reported, with clinical manifestations distinct from those typically found in adults.

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Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain

Critical Care ◽

10.1186/s13054-020-03332-4 ◽

2020 ◽

Vol 24 (1) ◽

Author(s):

Alberto García-Salido ◽

◽

Juan Carlos de Carlos Vicente ◽

Sylvia Belda Hofheinz ◽

Joan Balcells Ramírez ◽

...

Keyword(s):

Intensive Care ◽

Intensive Care Units ◽

Gastrointestinal Symptoms ◽

Pediatric Intensive Care ◽

Critically Ill Children ◽

Vasoactive Drugs ◽

Pediatric Intensive Care Units ◽

Neutrophil Lymphocyte Ratio ◽

Inflammatory Syndrome ◽

To Receive

Abstract Background Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection in children. We aimed to describe the characteristics of children admitted to Pediatric Intensive Care Units (PICUs) presenting with MIS-C in comparison with those admitted with SARS-CoV-2 infection with other features such as COVID-19 pneumonia. Methods A multicentric prospective national registry including 47 PICUs was carried out. Data from children admitted with confirmed SARS-CoV-2 infection or fulfilling MIS-C criteria (with or without SARS-CoV-2 PCR confirmation) were collected. Clinical, laboratory and therapeutic features between MIS-C and non-MIS-C patients were compared. Results Seventy-four children were recruited. Sixty-one percent met MIS-C definition. MIS-C patients were older than non-MIS-C patients (p = 0.002): 9.4 years (IQR 5.5–11.8) vs 3.4 years (IQR 0.4–9.4). A higher proportion of them had no previous medical history of interest (88.2% vs 51.7%, p = 0.005). Non-MIS-C patients presented more frequently with respiratory distress (60.7% vs 13.3%, p < 0.001). MIS-C patients showed higher prevalence of fever (95.6% vs 64.3%, p < 0.001), diarrhea (66.7% vs 11.5%, p < 0.001), vomits (71.1% vs 23.1%, p = 0.001), fatigue (65.9% vs 36%, p = 0.016), shock (84.4% vs 13.8%, p < 0.001) and cardiac dysfunction (53.3% vs 10.3%, p = 0.001). MIS-C group had a lower lymphocyte count (p < 0.001) and LDH (p = 0.001) but higher neutrophil count (p = 0.045), neutrophil/lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001) and procalcitonin (p < 0.001). Patients in the MIS-C group were less likely to receive invasive ventilation (13.3% vs 41.4%, p = 0.005) but were more often treated with vasoactive drugs (66.7% vs 24.1%, p < 0.001), corticosteroids (80% vs 44.8%, p = 0.003) and immunoglobulins (51.1% vs 6.9%, p < 0.001). Most patients were discharged from PICU by the end of data collection with a median length of stay of 5 days (IQR 2.5–8 days) in the MIS-C group. Three patients died, none of them belonged to the MIS-C group. Conclusions MIS-C seems to be the most frequent presentation among critically ill children with SARS-CoV-2 infection. MIS-C patients are older and usually healthy. They show a higher prevalence of gastrointestinal symptoms and shock and are more likely to receive vasoactive drugs and immunomodulators and less likely to need mechanical ventilation than non-MIS-C patients.

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Influence of sex on disease severity in children with COVID-19 and Multisystem Inflammatory Syndrome in Latin America

10.1101/2021.02.07.21251212 ◽

2021 ◽

Cited By ~ 2

Author(s):

Martin Brizuela ◽

Jacopo Lenzi ◽

Rolando Ulloa-Gutiérrez ◽

Antúnez-Montes Omar Yassef ◽

Jorge Alberto Rios Aida ◽

...

Keyword(s):

Latin America ◽

Disease Severity ◽

Latin American ◽

Pediatric Population ◽

Large Cohort ◽

Significant Difference ◽

American Children ◽

Inflammatory Syndrome

SummaryData from adult studies how that COVID-19 is more severe in men than women. However, no data are available for the pediatric population. For this reason, we performed this study aiming to understand if sex influenced disease severity and outcomes in a large cohort of latin-american children with COVID-19 and Multisystem Inflammatory Syndrome (MIS-C). We found that a higher percentage of male children developed MIS-C (8.9% vs 5% in females) and died (1.2% and 0.4% in females), although on multivariate adjusted analyses the only statistically significant difference was found in need of hospitalization, with females less frequently admitted compared with boys (25.6% vs 35.4%). This data are preliminary and need further independent studies to better assess the role of sex.

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COVID-19 Associated Multisystem Inflammatory Syndrome: A Systematic Review and Meta-analysis

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v19i6.4927 ◽

2020 ◽

Author(s):

Ashkan Baradaran ◽

Abdolreza Malek ◽

Nasrin Moazzen ◽

Zahra Abbasi Shaye

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Gastrointestinal Symptoms ◽

Multiple Organ ◽

Current Evidence ◽

Cardiac Complications ◽

Clinical Presentations ◽

Atypical Kawasaki Disease ◽

Novel Coronavirus ◽

Inflammatory Syndrome

The prevalence of multisystem inflammatory syndrome in children (MIS-C) has increased since the coronavirus disease 2019 (COVID-19) pandemic started. This study was aimed to describe clinical manifestation and outcomes of MIS-C associated with COVID-19. This systematic review and meta-analysis were conducted on all available literature until July 3rd, 2020. The screening was done by using the following keywords: (“novel coronavirus” Or COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus) and ("MIS-C" or "multisystem inflammatory" or Kawasaki). Data on gender, ethnicity, clinical presentations, need for mechanical ventilation or admission to intensive care unit (ICU), imaging, cardiac complications, and COVID-19 laboratory results were extracted to measure the pooled estimates. Out of 314 found articles, 16 articles with a total of 600 patients were included in the study, the most common presentation was fever (97%), followed by gastrointestinal symptoms (80%), and skin rashes (60%) as well as shock (55%), conjunctivitis (54%), and respiratory symptoms (39%). Less common presentations were neurologic problems (33%), and skin desquamation (30%), MIS-C was slightly more prevalent in males (53.7%) compared to females (46.3%). The findings of this meta-analysis on current evidence found that the common clinical presentations of COVID-19 associated MIS-C include a combination of fever and mucocutaneous involvements, similar to atypical Kawasaki disease, and multiple organ dysfunction. Due to the relatively higher morbidity and mortality rate, it is very important to diagnose this condition promptly.

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COVID-19 and Multisystem Inflammatory Syndrome in Latin American Children

The Pediatric Infectious Disease Journal ◽

10.1097/inf.0000000000002949 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Cited By ~ 2

Author(s):

Omar Yassef Antúnez-Montes ◽

Maria Isabel Escamilla ◽

Augusto Flavio Figueroa-Uribe ◽

Erick Arteaga-Menchaca ◽

Manuel Lavariega-Saráchaga ◽

...

Keyword(s):

Latin American ◽

American Children ◽

Inflammatory Syndrome

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Acute Abdomen and Multisystem Inflammatory Syndrome in Children with COVID-19: A Case Report and Review of Pathophysiology, Gastrointestinal Symptoms and Abdominal Radiology

Surgical Case Reports ◽

10.31487/j.scr.2021.08.01 ◽

2021 ◽

pp. 1-6

Author(s):

Noela Carrera-Guermeur ◽

Rosa-Maria Martin-Crespo-Izquierdo ◽

Hilda-Josefa Ramirez-Velandia ◽

Maria-Esmeralda Kuan-Arguello ◽

...

Keyword(s):

Acute Abdomen ◽

Scientific Information ◽

Gastrointestinal Symptoms ◽

Severe Form ◽

Point Of View ◽

Ultrasound Images ◽

Abdominal Radiology ◽

Total Incidence ◽

High Index Of Suspicion ◽

Inflammatory Syndrome

Introduction: Pediatric patients with coronavirus disease 2019 (COVID-19) account for less than 5% of the total incidence. The scientific literature reports that most patients are asymptomatic or present mild symptoms. However, they may only manifest gastrointestinal symptoms and even present an acute abdomen; a severe form of presentation has been reported, called multisystem inflammatory syndrome in children. Case Presentation: We report a 10-year-old girl who presents COVID-19 in the form of an acute abdomen because of severe sigmoiditis who developed multisystem inflammatory syndrome together with shock. The patient fully recovered without sequelae with medical treatment. We provide computed tomography and ultrasound images and review scientific information available on gastrointestinal COVID-19 pathophysiology from the pediatric point of view. Conclusion: A high index of suspicion is needed for diagnosing COVID-19 in the event of any pediatric acute abdomen during the pandemic, and screening should be undertaken even without an epidemiologic setting and in the absence of respiratory symptoms or radiologic chest signs because acute abdomen could be a clinical presentation of MIS-C in children.

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Case Report: Changes in Cytokine Kinetics During the Course of Disease in a Japanese Patient With Multisystem Inflammatory Syndrome in Children

Frontiers in Pediatrics ◽

10.3389/fped.2021.702318 ◽

2021 ◽

Vol 9 ◽

Author(s):

Satoshi Takasago ◽

Aiko Sakai ◽

Masaya Sugiyama ◽

Masashi Mizokami ◽

Hiromichi Hamada ◽

...

Keyword(s):

Kawasaki Disease ◽

Acute Myocarditis ◽

Severe Disease ◽

Gastrointestinal Symptoms ◽

Disease Status ◽

Classical Trajectory ◽

Course Of Disease ◽

Old Japanese ◽

Cervical Swelling ◽

Inflammatory Syndrome

Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that is reportedly linked to coronavirus disease 2019. Affected patients present with gastrointestinal symptoms and cardiovascular dysfunction, in addition to Kawasaki disease-like features, suggesting the potential for overlapping disease mechanisms. Kawasaki disease has been reported among individuals of East Asian ethnicities, whereas there is minimal clinical literature regarding the occurrence of MIS-C among individuals of Asian ethnicities. A few reports thus far have described changes in cytokine kinetics during the course of disease in patients with MIS-C. We followed the temporal cytokine kinetics in a 9-year-old Japanese girl who exhibited a classical trajectory of MIS-C. The patient exhibited right cervical swelling and pain, abdominal pain, vomiting, and lip reddening, which developed 31 days after she was diagnosed with severe acute respiratory syndrome coronavirus-2 infection. The patient was diagnosed with Kawasaki disease on her fifth day of illness; because she fulfilled the criteria for MIS-C, she was also diagnosed with this disease on her fifth day of illness. Her fever rapidly resolved upon administration of intravenous immunoglobulin, aspirin, and prednisolone. On the patient's sixth day of illness, she developed acute myocarditis, which was treated with two diuretics and one vasodilator; the myocarditis ameliorated within a few days. Analyses of temporal kinetics for 71 serum cytokines revealed several patterns of cytokine changes that were consistent with the patient's clinical course of disease. Importantly, there was a clear distinction between cytokines that did and did not decrease rapidly following post-treatment fever resolution. These findings may be useful for the assessment of disease status and selection of therapy in patients with similar symptoms; they may also provide insights for basic and clinical research regarding MIS-C.

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Secretory phospholipase A2 in SARS-CoV-2 infection and multisystem inflammatory syndrome in children (MIS-C)

Experimental Biology and Medicine ◽

10.1177/15353702211028560 ◽

2021 ◽

pp. 153537022110285

Author(s):

Frans A Kuypers ◽

Christina A Rostad ◽

Evan J Anderson ◽

Ann Chahroudi ◽

Preeti Jaggi ◽

...

Keyword(s):

Severe Disease ◽

Pediatric Intensive Care ◽

Cellular Damage ◽

Inflammasome Activation ◽

Igg Antibodies ◽

Secretory Phospholipase ◽

History Of ◽

Adults And Children ◽

Therapeutic Compounds ◽

Inflammatory Syndrome

Secretory phospholipase 2 (sPLA2) acts as a mediator between proximal and distal events of the inflammatory cascade. Its role in SARS-CoV-2 infection is unknown, but could contribute to COVID-19 inflammasome activation and cellular damage. We present the first report of plasma sPLA2 levels in adults and children with COVID-19 compared with controls. Currently asymptomatic adults with a history of recent COVID-19 infection (≥4 weeks before) identified by SARS-CoV-2 IgG antibodies had sPLA2 levels similar to those who were seronegative (9 ± 6 vs.17 ± 28 ng/mL, P = 0.26). In contrast, children hospitalized with severe COVID-19 had significantly elevated sPLA2 compared with those with mild or asymptomatic SARS-CoV-2 infection (269 ± 137 vs. 2 ± 3 ng/mL, P = 0.01). Among children hospitalized with multisystem inflammatory syndrome in children (MIS-C), all had severe disease requiring pediatric intensive care unit (PICU) admission. sPLA2 levels were significantly higher in those with acute illness <10 days versus convalescent disease ≥10 days (540 ± 510 vs. 2 ± 1, P = 0.04). Thus, sPLA2 levels correlated with COVID-19 severity and acute MIS-C in children, implicating a role in inflammasome activation and disease pathogenesis. sPLA2 may be a useful biomarker to stratify risk and guide patient management for children with acute COVID-19 and MIS-C. Therapeutic compounds targeting sPLA2 and inflammasome activation warrant consideration.

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The “Golden Hours” Algorithm For the Management of the Multisystem Inflammatory Syndrome in Children (MIS-C)

Global Pediatric Health ◽

10.1177/2333794x21990339 ◽

2021 ◽

Vol 8 ◽

pp. 2333794X2199033

Author(s):

Sanaa Mahmoud ◽

Eman M Fouda ◽

Alyaa Kotby ◽

Hanan M Ibrahim ◽

Mervat Gamal ◽

...

Keyword(s):

Gastrointestinal Symptoms ◽

Pediatric Intensive Care ◽

Risk Groups ◽

Intravenous Immunoglobulins ◽

High Risk Group ◽

Circulatory Support ◽

Clinical Approach ◽

Number Of Children ◽

Isolation Ward ◽

Inflammatory Syndrome

The global concern of increasing number of children presenting with multisystem inflammatory syndrome in children (MIS-C) related to the coronavirus disease (COVID-19) has escalated the need for a case-oriented clinical approach that provides timely diagnosis and management. The aim of this study is to share our experience in managing 64 MIS-C patients of North African ethnicity guided by a risk-based algorithm. Sixty-four patients met the inclusion criteria, 19 (30%) patients were categorized as mild and moderate risk groups and cared for in an isolation ward and 45 patients who belonged to the high-risk group (70%) were admitted to the pediatric intensive care unit (PICU). Positive laboratory evidence of COVID-19 was found in 62 patients. Fever and dysfunction in 2 or more organs were confirmed in all cases (100%). Fifty patients (78%) presented with gastrointestinal symptoms, meanwhile only 10 patients (16%) had respiratory manifestations. Cardiac involvement was reported in 55 (86%) cases; hypotension and shock were found in 45 patients (70%) therein circulatory support and mechanical ventilations were needed for 45 and 13 patients respectively. Intravenous immunoglobulins (IVIG) were used for all cases and methylprednisolone was used in 60 patients (94%). Fifty-eight (91%) patients were discharged home after an average of 9 days of hospitalization. The mortality rate was 9% (6 patients). Conclusion. A single Egyptian center experience in the management of MIS-C patients guided by a proposed bed side algorithm is described. The algorithm proved to be a helpful tool for first-line responders, and helped initiate early treatment with IVIG.

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A descriptive study on multisystem inflammatory syndrome in children in a single center in West Michigan

Pediatric Rheumatology ◽

10.1186/s12969-021-00658-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jonathan Shabab ◽

Allysen Dubisky ◽

Ambaris Singh ◽

Megan Crippen ◽

Khalid Abulaban ◽

...

Keyword(s):

Intensive Care ◽

Care Center ◽

Tertiary Care ◽

Gastrointestinal Symptoms ◽

Case Series ◽

Pediatric Intensive Care ◽

Chi Square ◽

Significant Difference ◽

Threatening Condition ◽

Inflammatory Syndrome

Abstract Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare hyperinflammatory condition that occurs following SARS-CoV-2 infection. There is a paucity of research describing risk factors, optimal management, and outcomes of this life-threatening condition. Methods This is a case series of 26 patients diagnosed with MIS-C in a West Michigan pediatric tertiary care center from April 2020 to February 2021. We describe the clinical, imaging, and laboratory characteristics of these patients and detail their treatments and outcomes with comparisons between Pediatric Intensive Care Unit (PICU) and non-PICU patients. Categorical testing utilized Chi-square and Fisher’s Exact tests. Comparison between groups used T-tests or Kruskal-Wallis. Results Fifteen patients (57%) required intensive care. There was no statistically significant difference in demographics between PICU and non-PICU patients, however all Black patients required intensive care. Gastrointestinal symptoms were present in 22 patients (84%). Seventeen patients (65%) had Kawasaki-like features and 12 (46%) developed coronary artery dilation. Patients requiring intensive care were less likely to have a reported history of COVID-19 disease or exposure (p = 0.0362). Statistically significant differences were also noted in peak ferritin (p = 0.0075), procalcitonin, and BNP in those who required intensive care. Conclusions Although overlap exists with other hyperinflammatory conditions, our study provides further evidence that MIS-C is a distinct, albeit heterogenous, disorder with various degrees of cardiac involvement. Anakinra, in conjunction with steroid use, appears to be effective and safe in the treatment of MIS-C. This report identifies procalcitonin, peak ferritin, and BNP as potentially useful biomarkers for severity of disease.

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