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

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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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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Celiac disease in first degree relatives of celiac children

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032012000300007 ◽

2012 ◽

Vol 49 (3) ◽

pp. 204-207 ◽

Cited By ~ 6

Author(s):

Andreia Oliveira ◽

Eunice Trindade ◽

Marta Tavares ◽

Rosa Lima ◽

Mariana Terra ◽

...

Keyword(s):

Celiac Disease ◽

High Risk ◽

Screening Test ◽

Tissue Transglutaminase ◽

Gastrointestinal Symptoms ◽

Rapid Test ◽

Risk Groups ◽

High Titre ◽

High Risk Group ◽

First Degree Relatives

CONTEXT - The first degree relatives of celiac patients represent a high risk group for the development of this disorder, so their screening may be crucial in the prevention of long-term complications. OBJECTIVE - In order to determine the prevalence of celiac disease in a group of first degree relatives of children with proven gluten intolerance, we conducted a prospective study that consisted in the screening of celiac disease, using a capillary immunoassay rapid test that allows a qualitative detection of IgA antibody to human recombinant tissue transglutaminase (IgA-TTG). METHODS - When the screening test was positive subjects were advised to proceed with further investigation. The screening test was performed in 268 first degree relatives (143 mothers, 89 fathers, 36 siblings) corresponding to 163 children with celiac disease. RESULTS - Screening test was positive in 12 relatives (4.5%), of which 1 refused to continue the investigation. In the remaining 11 relatives celiac disease was diagnosed in 7 cases (2.6%, 5 mothers, 2 fathers) who had a median age of 39 years (27-56 years), mild gastrointestinal symptoms, high titre of IgA-TTG and histology abnormalities confirming the diagnosis. All these patients are currently on a gluten-free diet. CONCLUSION - The prevalence of celiac disease among first degree relatives (2.6%) was 5 times higher than that in the general population. Although the recommendations for screening asymptomatic high risk groups, such as first degree relatives, are not unanimous the early diagnosis is crucial in preventing complications, including nutritional deficiency and cancer.

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X-Linked Lymphoproliferative Disease Mimicking Multisystem Inflammatory Syndrome in Children—A Case Report

Frontiers in Pediatrics ◽

10.3389/fped.2021.691024 ◽

2021 ◽

Vol 9 ◽

Author(s):

Seraina Prader ◽

Nicole Ritz ◽

Frédéric Baleydier ◽

Maya C. Andre ◽

Noémie Stähli ◽

...

Keyword(s):

Case Report ◽

Severe Disease ◽

Intravenous Immunoglobulins ◽

Lymphoproliferative Disease ◽

Number Of Children ◽

Barr Virus ◽

Reactive Protein ◽

Fatal Liver Failure ◽

Epstein Barr ◽

Inflammatory Syndrome

Most children with a SARS-CoV-2 infection are asymptomatic or exhibit mild symptoms. However, a small number of children develop features of substantial inflammation temporarily related to the COVID-19 also called multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), clinically similar to Kawasaki disease, toxic shock syndrome and hemophagocytic lymphohistiocytosis (HLH). It is well-known that genetic pre-disposition plays an important role in virally-triggered diseases such as Epstein-Barr virus (EBV)-associated HLH, while this has not yet been established for patients with MIS-C. Here we describe a male patient fulfilling the diagnostic criteria of MIS-C, who was initially treated according to current consensus guidelines. Presence of hypofibrinogenemia, normal lymphocyte counts and C-reactive protein, but substantial hyperferritinemia distinguish this patient from others with MIS-C. The clinical course following initial presentation with acute respiratory distress syndrome was marked by fatal liver failure in the context of EBV-associated HLH despite treatment with steroids, intravenous immunoglobulins, interleukin (IL)-1 receptor blockade and eventually HLH-directed treatment. X-linked lymphoproliferative disease type 1 (XLP1), a subtype of primary HLH was diagnosed in this patient post-mortem. This case report highlights the importance of including HLH in the differential diagnosis in MIS-C with severe disease course to allow specific, risk-adapted treatment and genetic counseling.

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Novel Coronavirus Infection in an Infant with Intussusception

Global Pediatric Health ◽

10.1177/2333794x211012978 ◽

2021 ◽

Vol 8 ◽

pp. 2333794X2110129

Author(s):

Juan Felipe Osorno ◽

Manuel Giraldo ◽

Andrés Felipe Marín ◽

Luis Mauricio Figueroa

Keyword(s):

Viral Infections ◽

Gastrointestinal Symptoms ◽

Intestinal Resection ◽

Pediatric Intensive Care ◽

Postoperative Phase ◽

Clinical Approach ◽

Coronavirus Infection ◽

Common Sign ◽

Novel Coronavirus ◽

The Right

Background. Intussusception is the leading cause of intestinal obstruction in children under 4 years of age. Viral infections are the associated etiology in most cases, SARS-CoV-2 thereby being a plausible cause, although only 5 cases have been reported worldwide with both entities. We report a case of an infant with Intussusception and covid-19, its clinical approach, and surgical outcomes, throughout a retrospective review of electronic medical chart history with the authorization of the Ethics Committee on research of the “Hospital Universitario del Valle” and endorsement for publication. Case report. It is an 8-month-old male patient with 72 hours of fever 100.4°F; bloody diarrheal stools; episodic abdominal pain; signs of peritoneal irritation and sensation of a mass in the right quadrants of the abdomen. Intussusception confirmed by ultrasound led to surgery, with SARS-CoV-2 infection as a possible differential diagnosis. Surgical findings reported intussusception of the transverse colon, peritonitis, and intestinal ischemia of distal ileum and right colon, for which intestinal resection with consequent ileostomy and a mucous fistula was performed. Positive SARS-CoV-2 RT-PCR test result was confirmed. Pediatric intensive care unit support took place at the initial postoperative phase, and eventual intestinal, with enteral feeding tolerance at the fourth day, and respiratory improvement came off within the first week of medical and surgical treatment. Conclusion. Gastrointestinal symptoms are often the leading manifestations of COVID-19 in children, which can be isolated or as a common sign of a concomitant pathology such as intussusception, and they could also have a causal relationship.

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Kawasaki-like disease and acute myocarditis in the SARS-CoV-2 pandemic – reports of three adolescents

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2020.5037 ◽

2020 ◽

Author(s):

Stasa Krasic ◽

Sergej Prijic ◽

Predrag Minic ◽

Gordana Petrovic ◽

Dejan Nesic ◽

...

Keyword(s):

Early Recognition ◽

Acute Myocarditis ◽

Systolic Dysfunction ◽

Acute Infection ◽

Clinical Signs ◽

Gastrointestinal Symptoms ◽

Intravenous Immunoglobulins ◽

Nasopharyngeal Swab ◽

Term Outcome ◽

Inflammatory Syndrome

The novel coronavirus disease (COVID-19) may induce multisystem inflammatory syndrome in children, which may be associated with Kawasaki-like disease, and cardiac injury. In this study, we presented three male adolescents with multisystem inflammatory syndrome and myocardial injury admitted to the hospital during the peak of COVID-19 pandemic. All of the three patients had a history of fever, gastrointestinal symptoms, polymorph rash, non-exudative conjunctivitis, and signs of acute myocarditis. One of them had renal failure. Previously, they did not have an acute infection. Upon admission, they were hypotensive and tachycardic. A nasopharyngeal swab for SARS-CoV-2 on reverse transcription-polymerase chain reaction (PCR) assay was negative, but neutralizing viral antibodies were positive. In combination with blood tests, ECG, echocardiography and computerized tomography (CT), a multisystem inflammatory syndrome associated with acute myocarditis with mild to moderate systolic dysfunction and dilated coronary arteries were diagnosed. Two of three patients had shock syndrome and required inotropic support. All patients were treated with intravenous immunoglobulins. The second patient had a fever up to 102.2°F (39°C) three days after intravenous immunoglobulins. Further, he was treated according to protocols for refractory Kawasaki disease, with an intravenous methylprednisolone pulse therapy and aspirin. After a few hours, he became afebrile and the clinical signs disappeared. The favorable short-term outcome may reflect the early recognition and adequate therapy; however, the long-term outcomes are currently unknown.

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A Retrospective Comparative Analysis of Factors Affecting the Decision and Outcome of Initial Intravenous Immunoglobulin Alone or Intravenous Immunoglobulin Plus Methylprednisolone Use in Children With the Multisystem Inflammatory Syndrome

10.21203/rs.3.rs-1128254/v1 ◽

2021 ◽

Author(s):

İlker Devrim ◽

Elif Böncüoğlu ◽

Elif Kıymet ◽

Şahika Şahinkaya ◽

Miray Yılmaz Çelebi ◽

...

Keyword(s):

Intravenous Immunoglobulin ◽

Pediatric Intensive Care ◽

Serum Levels ◽

Intravenous Immunoglobulins ◽

Treatment Modalities ◽

Double Blind ◽

Factors Affecting ◽

Group I ◽

Group Ii ◽

Inflammatory Syndrome

Abstract Background: Use of intravenous immunoglobulins (IVIG) with or without methylprednisolone is the most preferred therapeutic strategy for the multisystem inflammatory syndrome in children (MIS-C). This study aimed to compare the use of IVIG plus methylprednisolone vs IVIG alone in children with MIS-C. Methods: This retrospective cohort study was conducted during the period between April 1, 2020, and November 1, 2021. All children with MIS-C were included in the study. The patients were divided in two groups according to whether they were administered IVIG alone or IVIG plus methylprednisolone as an initial treatment for MIS-C. While the patients in group I were administered IVIG with a dosage of 2 gr/kg, the patients in group II were administered IVIG (dosage of 2 gr/kg) plus methylprednisolone (2 mg/kg/day). The re-occurrence of fever, duration of hospital stay, admission to pediatric intensive care unit were compared between these two groups. Results: A cohort of 91 patients under 18 years old and diagnosed as MIS-C was included in the study. Of these patients, 42 (46.2%) were in IVIG alone group. (group I) and 49 (53.8%) were in IVIG plus methylprednisolone (group II). The ratio of severe MIS-C was 36.7% for patients in the group II and significantly higher compared to the rate of severe MIS-C patients in the group I (9.5%) (p=0.01). The rate of hypotension was significantly higher in the group II (30.6 %) compared to the group I (9.5%) (p=0.014). Moreover, the mean serum levels of C-reactive protein were significantly higher for the patients in group II. The re-occurrence of fever was 26.5% in the group II and 33.3% in the group, however this difference was not statistically significant (p>0.05). Conclusions: The decision of the treatment choice of patients with MIS-C should be individually evaluated. In the clinically severe MIS-C patients who were with hypotension, and/or admitted to PICU should be treated with IVIG plus methylprednisolone. However, randomized double-blind studies are required for the treatment modalities of children with MIS-C.

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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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An Arab Adolescent with Multisystem Inflammatory Syndrome Associated with COVID-19: A Report from Syria

Avicenna Journal of Medicine ◽

10.1055/s-0041-1734387 ◽

2021 ◽

Author(s):

Jaafer Zaino ◽

Abdullah Bakri ◽

Amani Al Sayed Ahmad ◽

Ghadeer Hadba

Keyword(s):

Inflammatory Markers ◽

Gastrointestinal Symptoms ◽

Epidemiological Data ◽

Intravenous Immunoglobulins ◽

Arab Countries ◽

Rt Pcr ◽

High Grade Fever ◽

Multiorgan Dysfunction ◽

Laboratory Profile ◽

Inflammatory Syndrome

AbstractMultisystem inflammatory syndrome in children (MIS-C) is a rare and critical condition that affects children following exposure to severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection, leading to multiorgan dysfunction and shock. MIS-C has been reported from different parts of the world but rarely from Arab countries. In this report, we describe a 15-year-old Arab boy who was admitted to the ICU during the surge of Coronavirus transmission in Syria with a clinical picture consistent with MIS-C, including high-grade fever, gastrointestinal symptoms, rash, multiorgan dysfunction, and shock. Laboratory profile showed significant elevation of inflammatory markers, negative SARS-CoV-2 RT-PCR testing but positive serologic testing for SARS-CoV-2. The patient received intravenous immunoglobulins (IVIG) and glucocorticoids with remarkable cardiac improvement and significant alleviation in inflammatory markers. To our knowledge, this is the first reported case of MIS-C from Syria, which adds to the epidemiological data about this new syndrome.

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First Tunisian cluster admissions of critically ill patients with multisystem inflammatory syndrome in children (MIS-C)

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2021.023 ◽

2021 ◽

Vol 13 (1) ◽

pp. e2021023

Author(s):

Aida Borgi

Keyword(s):

Critically Ill ◽

Gastrointestinal Symptoms ◽

Pediatric Intensive Care ◽

Emerging Disease ◽

Critically Ill Children ◽

Laboratory Findings ◽

Methyl Prednisolone ◽

Laboratory Test Results ◽

Severity Scores ◽

Inflammatory Syndrome

Background: Multisystem inflammatory syndrome in children (MIS-C) is a new serious emerging disease that is temporally related to previous exposure to coronavirus infection disease (COVID-19). Aim: To describe the clinical features, laboratory findings, therapies and outcomes for the first Tunisian cluster admissions of critically ill children with severe MIS-C. Methods: Retrospective study conducted between 01 November and 30 November 2020 We included 8 children aged less than 15 years who were admitted to our pediatric intensive care and met the criteria for MIS-C according to the WHO definition case. We reviewed the medical records of all patients to collect demographic and clinical data, severity scores, laboratory test results, echocardiographic findings, treatment, and outcomes. Results: All children were previously fit and well. Seven patients were boys. Known exposure to COVID-19 was reported in 4 cases. Fever and gastrointestinal symptoms were reported in all cases. Five patients had marked abdominal pain and were examined by the surgeon for a possible appendicitis. Seven patients had diarrhea. On examination, we found a rash (n=7), a conjunctivitis (n=7), a cheilitis (n=5) and a meningism (n=3). We reported cardiac dysfunction in 7 cases and a shock with hypotension in 3 cases. All patients received immunoglobulins, methyl prednisolone and a low dose of aspirine. No deaths occurred. Conclusion: We reported here the first Tunisian cluster admissions of 8 critically ill children with MIS-C to highlight the increase of a new severe emerging disease with an evidence of prior COVID-19 infection in older children.

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Multisystem Inflammatory Syndrome in Children and Adolescents (MIS-C) under the Setting of COVID-19: A Review of Clinical Presentation, Workup and Management

Infectious Diseases Research and Treatment ◽

10.1177/11786337211026642 ◽

2021 ◽

Vol 14 ◽

pp. 117863372110266

Author(s):

Ayesha Farooq ◽

Fatima Alam ◽

Asma Saeed ◽

Farooq Butt ◽

Muhammad Azeem Khaliq ◽

...

Keyword(s):

Kawasaki Disease ◽

Children And Adolescents ◽

Past History ◽

Multiorgan Failure ◽

Gastrointestinal Symptoms ◽

Respiratory Illness ◽

Intravenous Immunoglobulins ◽

Cardiac Complications ◽

Inflammatory Syndrome

Earlier in its course, SARS-CoV-2 was primarily identified to cause an acute respiratory illness in adults, the elderly and immunocompromised, while children were known to be afflicted with milder symptoms. However, since mid-April of 2020, latent effects of the virus have begun emerging in children and adolescents, which is characterised by a multisystem hyperinflammatory state; thus, the term Multisystem Inflammatory Syndrome in Children (MIS-C) was introduced by the WHO and CDC. The syndrome manifests itself approximately 4 weeks after COVID-19 infection, with symptoms mimicking Kawasaki Disease and Kawasaki Disease Shock Syndrome. Demographically, MIS-C peaks in children aged 5 to 14 years, with clusters in Europe, North and Latin America seen, later followed by Asia. Although the exact pathophysiology behind the syndrome is unknown, recent studies have proposed a post-infectious immune aetiology, which explains the increased levels of immunoglobulins seen in affected patients. Patient presentation includes, but is not limited to, persistent fever, rash, gastrointestinal symptoms and cardiac complications including myocarditis. These patients also have raised inflammatory markers including C reactive protein, ferritin and interleukin-6. In poorly controlled patients, the syndrome can lead to multiorgan failure and death. The mainstay of treatment includes the use of intravenous immunoglobulins, steroids, immune modulators and aspirin. Adjunct therapy includes the use of low molecular weight heparin or warfarin for long term anticoagulation. Currently very little is known about the syndrome, highlighting the need for awareness amongst healthcare workers and parents. Moreover, with increased cases of COVID-19 as a result of the second wave, it is essential to keep MIS-C in mind when attending patients with a past history of COVID-19 exposure or infection. Additionally, once these patients have been identified and treated, strict follow-up must be done in order carry out long term studies, and to identify possible sequelae and complications.

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