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1.
J Allergy Clin Immunol ; 2022.
Article in English | ScienceDirect | ID: covidwho-2031405

ABSTRACT

BACKGROUND: Most SARS-CoV-2 infected individuals are asymptomatic or only show a mild disease. In about 10% of cases, the infection leads to hypoxemic pneumonia, although it is much more rare in children. OBJECTIVE: We evaluated 31 young patients (0.5-19 years) who had pre-existing inborn errors of immunity (IEI) but lacked a molecular diagnosis and were later diagnosed with COVID-19 complications. METHODS: Genetic evaluation by whole-exome sequencing was performed in all patients. SARS-CoV-2 specific antibodies, autoantibodies against type I interferons (IFNs) and inflammatory factors in plasma were measured. We also reviewed COVID-19 disease severity/outcome in reported IEI patients. RESULTS: A potential genetic cause of the IEI was identified in 28 patients (90.3%), including mutations that may affect IFN signaling, T and B cell function, the inflammasome, and the complement system. Fourteen of the patients tested (66%) had detectable virus-specific antibodies and two patients (6.8%) had autoantibodies neutralizing type-I IFNs. Five patients (16.1%) fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children (MIS-C). Eleven patients (35.4%) died due to COVID-19 complications. Altogether at least 381 IEI children with COVID-19 have been reported in the literature till date. Although many asymptomatic or mild patients may not have been reported, severe presentation of COVID-19 was observed in 23.6% of the published cases and the mortality rate was 8.7%. CONCLUSION: Young patients with pre-existing IEI may have a higher mortality as compared to children without IEI when infected with SARS-CoV-2. Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to develop better strategies for prevention and treatment of severe COVID-19 disease and complications in pediatric patients.

2.
Clinical Immunology ; : 109106, 2022.
Article in English | ScienceDirect | ID: covidwho-2003938

ABSTRACT

Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infections that occurs in the pediatric population. We sought to characterize T cell responses in MIS-C compared to COVID-19 and pediatric hyperinflammatory syndromes. MIS-C was distinct from COVID-19 and hyperinflammatory syndromes due to an expansion of T cells expressing TRBV11–2 that was not associated with HLA genotype. Children diagnosed with MIS-C, but who were negative for SARS-CoV-2 by PCR and serology, did not display Vβ skewing. There was no difference in the proportion of T cells that became activated after stimulation with SARS-CoV-2 peptides in children with MIS-C compared to convalescent COVID-19. The frequency of SARS-CoV-2-specific TCRs and the antigens recognized by these TCRs were comparable in MIS-C and COVID-19. Expansion of Vβ11–2+ T cells was a specific biomarker of MIS-C patients with laboratory confirmed SARS-CoV-2 infections. Children with MIS-C had robust antigen-specific T cell responses to SARS-CoV-2.

3.
J Clin Med ; 11(15)2022 Aug 08.
Article in English | MEDLINE | ID: covidwho-1990298

ABSTRACT

BACKGROUND: Two years after the first cases, critical gaps remain in identifying prognostic factors in multisystem inflammatory syndrome in children (MIS-C). METHODS: This retrospective study included 99 patients with MIS-C hospitalized between August 2020 and March 2022 in a pediatric tertiary center. The patients were divided into two groups according to clinical severity (low- and high-risk). Prognostic values of baseline clinical and laboratory characteristics were evaluated with advanced statistical analysis, including machine learning. RESULTS: Sixty-three patients were male, and the median age was 83 (3-205) months. Fifty-nine patients (59.6%) were low-risk cases. Patients aged six years and over tended to be at higher risk. Involvement of aortic or tricuspid valve or >1 valve was more frequent in the high-risk group. Mortality in previously healthy children was 3.2%. Intensive care unit admission and mortality rate in the high-risk group were 37.5% and 7.5%, respectively. At admission, high-risk patients were more likely to have reduced lymphocyte count and total protein level and increased brain natriuretic peptide (BNP), ferritin, D-dimer, and troponin concentrations. The multiple logistic regression model showed that BNP, total protein, and troponin were associated with higher risk. When the laboratory parameters were used together, BNP, total protein, ferritin, and D-dimer provided the highest contribution to the discrimination of the risk groups (100%, 89.6%, 85.6%, and 55.8%, respectively). CONCLUSIONS: Our study widely evaluates and points to some clinical and laboratory parameters that, at admission, may indicate a more severe course. Modeling studies with larger sample groups are strongly needed.

4.
Pediatr Nephrol ; 2022 Aug 09.
Article in English | MEDLINE | ID: covidwho-1982158

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.

5.
J Pediatric Infect Dis Soc ; 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1973209

ABSTRACT

In this cohort of 42 adolescents with a previous multisystem inflammatory syndrome (MIS-C) diagnosis, 32 (76.2%) were vaccinated with COVID-19 vaccines, with a low incidence of relevant adverse events. More importantly, no new MIS-C or myocarditis occurred after a median of 10 weeks (range 5.3-19.7) post-vaccination.

6.
Vaccines (Basel) ; 10(7)2022 Jul 16.
Article in English | MEDLINE | ID: covidwho-1939057

ABSTRACT

The SARS-CoV-2 vaccine roll-out has been successful around the world. However, there are increasing concerns about adverse events. We report two pediatric cases of Multisystem-Inflammatory-Syndrome (MIS-C) with neurological involvement that occurred after SARS-CoV-2 vaccination and unknown recent SARS-CoV-2 infection. Brain magnetic resonance revealed mild-encephalopathy with reversible-splenial-lesion in both cases and complete resolution within 4 weeks. In conclusion, this report aims to describe rare emerging clinical entities that can help pediatricians to make an early diagnosis and to provide appropriate treatment. Multisystem-Inflammatory-Syndromes following COVID-19 vaccination remain rare events. When a history of a recent contact with SARS-CoV-2 is present, a careful evaluation by the clinicians in charge of immunization activities is suggested prior to proceeding with the vaccination.

7.
J Clin Immunol ; 2022 Jul 11.
Article in English | MEDLINE | ID: covidwho-1930476

ABSTRACT

A 10-month-old boy was diagnosed with X-linked lymphoproliferative syndrome type 2 due to X-linked inhibitor of apoptosis deficiency after presenting with failure to thrive and refractory inflammatory bowel disease. He underwent a matched unrelated donor stem cell transplant with reduced intensity conditioning at 16 months. At 27 months, he presented with an atypical inflammatory syndrome in the setting of recent COVID-19 infection, Epstein-Barr viremia, and low chimerism (7.3%). He recovered after treatment with intravenous immunoglobulin and steroids.

8.
Int J Artif Organs ; : 3913988221111179, 2022 Jul 13.
Article in English | MEDLINE | ID: covidwho-1927988

ABSTRACT

Multisystem inflammatory syndrome (MIS-C) is a new severe clinical condition that has emerged during the COVID-19 pandemic. MIS-C affects children and the young usually after a mild or asymptomatic COVID-19 infection. MIS-C has a high tropism for the cardiovascular system with need for inotropes and vasopressor support in 62% of cases. As of today a mortality from 1.5% to 1.9% related to MIS-C is reported. Hemoadsorption via the inflammatory mediator adsorber CytoSorb (CytoSorbents Europe, Berlin Germany) has been used as adjunctive therapy with the aim to restore the host response in septic shock and other hyper-inflammatory syndromes. We present the clinical experience of an adolescent boy with a refractory shock secondary to left ventricular dysfunction (LVD) in the context of MIS-C, treated with hemoadsorption, and continuous kidney replacement therapy (CKRT) in combination with immunomodulatory therapies. The therapeutic strategy resulted in hemodynamic and clinical stabilization as well as control of the hyperinflammatory response. Treatment appeared to be safe and feasible. Our findings are in line with previously published clinical cases on Cytosorb use in MIS-C showing the beneficial role of the hemoperfusion with Cytosorb in severe MIS-C to manage the cytokine storm. We provide an analysis and comparison of recent evidence on the use of hemoadsorption as an adjuvant therapy in critically ill children with severe forms of MIS-C, suggesting this blood purification strategy could be a therapeutic opportunity in severe LVD due to MIS-C, sparing the need for extracorporeal membrane oxygentation (ECMO) and other mechanical cardiocirculatory supports.

9.
Cureus ; 14(4): e24348, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1863276

ABSTRACT

Coronary artery dilatation has been observed with coronavirus disease 2019 (COVID-19)-associated multisystem inflammatory syndrome in children (MIS-C), which is more common in those with Kawasaki-like disease. MIS-C is a clinical syndrome in children and adolescents; its signs and symptoms, as well as cardiac manifestations, are similar to Kawasaki diseases, such as coronary artery dilation, coronary aneurysms, and ventricular dysfunction. The occurrence of coronary artery dilatation in asymptomatic pediatric patients following COVID-19 infection has not been well documented in the literature. Thus, in this article, we present four cases of coronary artery dilation in children with a past history of COVID-19 infection who had very few or no symptoms and were referred to us for vague chest pain and palpitation. As a result, a high index of suspicion is required, and any patient complaining of chest pain and palpitation with a history of COVID-19 exposure should not be ignored and be given proper coronary artery evaluation. This article also raises the question of whether every child infected with COVID-19 should have an echocardiogram.

10.
IDCases ; 28: e01493, 2022.
Article in English | MEDLINE | ID: covidwho-1851185

ABSTRACT

Pediatric multisystem inflammatory syndrome (MIS-C) is a disease that presents mainly in older children after coronavirus disease 2019 (COVID-19) and is associated with Kawasaki-like symptoms and multiple-organ failure. The number of cases of MIS-C has increased since April 2020, with reports mainly from Europe and the United States. The reason is unclear, but few cases of MIS-C have been reported in Asian countries, including Japan. No treatment has been established for MIS-C. In this study, we report the case of a young boy treated with IVIg for MIS-C by measuring the cytokine profile over time. A 4-year-old boy presented with Kawasaki disease-like symptoms 28 days after a positive result from polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), meeting the World Health Organization criteria for MIS-C diagnosis. Blood tests showed lower levels of C-reactive protein and ferritin, and no decrease in lymphocyte count (<1000/µL) or more increase in fibrinogen than those reported in Japan for MIS-C in school-aged children and older. Neopterin, interleukin (IL)-6, IL-18, soluble tumor necrosis factor receptor (sTNF-R)I and sTNF-RII were all high at disease onset, but neopterin, IL-6, and sTNF-RII rapidly decreased with fever resolution after the second dose of IVIg, while IL-18 and sTNF-RI decreased bimodally. As far as we can determine, this case represents the youngest identified in Japan. The key point of difference between MIS-C and Kawasaki disease is older age in MIS-C, but attention is also needed in infants.

11.
Cureus ; 14(4): e24042, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1847663

ABSTRACT

Multisystem inflammatory syndrome (MIS) after a primary infection with coronavirus disease 2019 (COVID-19) was first recognized in 2020 and presents with similar symptoms as Kawasaki disease, toxic shock syndrome, and macrophage activation syndrome/secondary hemophagocytic lymphohistiocytosis. In children, it is called multisystem inflammatory syndrome in children (MIS-C); in adults, it is termed multisystem inflammatory syndrome in adults (MIS-A). This case offers a unique presentation of MIS in a 20-year-old young adult, who turned 21 years old one week after his presentation. He fits the criteria for MIS-C and MIS-A according to the Centers for Disease Control and World Health Organization, respectively. Initial symptoms in the emergency department included headache, neck stiffness, and fever with diffuse rash. Other symptoms consistent with MIS-C/A developed rapidly later during the course of the disease.

12.
Front Mol Biosci ; 9: 804109, 2022.
Article in English | MEDLINE | ID: covidwho-1834464

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has led to huge concern worldwide. Some SARS-CoV-2 infected patients may experience post-COVID-19 complications such as multisystem inflammatory syndrome, defined by symptoms including fever and elevated inflammatory markers (such as elevation of C reactive protein (CRP), erythrocyte sedimentation rate, fibrinogen, procalcitonin test, D-dimer, ferritin, lactate dehydrogenase or IL-6, presence of neutrophilia, lymphopenia, decreased albumin, and multiple organ dysfunction). Post-COVID-19 complications may also manifest as autoimmune diseases such as Guillain-Barré syndrome and systemic lupus erythematosus. Signaling disorders, increased inflammatory cytokines secretion, corticosteroid use to treat COVID-19 patients, or impaired immune responses are suggested causes of autoimmune diseases in these patients. In this review, we discuss the molecular and pathophysiological mechanisms and therapeutic opportunities for multisystem inflammatory syndrome and autoimmune diseases following SARS-CoV-2 infection with the aim to provide a clear view for health care providers and researchers.

13.
Children (Basel) ; 9(5)2022 Apr 28.
Article in English | MEDLINE | ID: covidwho-1820184

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been an emerging, rapidly evolving situation in China since late 2019 and has even become a worldwide pandemic. The first case of severe childhood novel coronavirus pneumonia in China was reported in March 2020 in Wuhan. The severity differs between adults and children, with lower death rates and decreased severity for individuals under the age of 20 years. Increased cases of Kawasaki disease (KD) have been reported from New York City and some areas of Italy and the U.K., with almost a 6-10 times increase when compared to previous years. We conducted this study to compare characteristics and laboratory data between KD and COVID-19 in children. METHODS: We obtained a total of 24 children with COVID-19 from a literature review and 268 KD cases from our hospital via retrospective chart review. RESULTS: We found that patients with KD have higher levels of white blood cells (WBCs), platelets, neutrophil percentage, C-reactive protein (CRP), procalcitonin, and aspartate aminotransferase (AST) and a higher body temperature, while patients with COVID-19 have a higher age, hemoglobin levels, and lymphocyte percentage. After performing multiple logistic regression analysis, we found that age, WBCs, platelets, procalcitonin, and AST are identical markers for distinguishing COVID-19 from KD in children. CONCLUSION: In this COVID-19 pandemic period, clinicians should pay attention to children with COVID-19 infection when high WBC, platelet, procalcitonin, and AST values are present in order to provide early diagnosis for KD or multisystem inflammatory syndrome in children (MIS-C).

14.
Pediatriya ; 61(2):57-61+7, 2021.
Article in Russian | Scopus | ID: covidwho-1790500

ABSTRACT

Multisystem Inflammatory Syndrome in children related to COVID-19 (MIS-C) is a new condition the aftermath of which is yet to be studied both in Bulgaria and globally. We present a 15 years old patient with MIS-C, diagnosed with acute abdomen, operated and consequently treated for septic shock syndrome, with late diagnosis and favorable outcome with standard treatment at a Pediatric Intensive Care unit. Early detection and timely diagnosis by testing for early inflammatory markers such as procalcitonin, serological testing of IgM and IgG antibodies for SARS-CoV-2 and multidisciplinary collaboration can significantly alter the complications of this serious condition. Clinical experience and standard therapeutic strategies will decrease the mortality, the need of intensive care as well as prevent the long-term consequences in the affected patients. © 2021 Academy of Medicine. All rights reserved.

15.
Pediatric Medicine ; 5, 2022.
Article in English | Scopus | ID: covidwho-1780390

ABSTRACT

Background and Objective: Children with SARS-CoV-2 infection were paid little attention to during the early stages of the outbreak because of low morbidity as well as mild clinical symptoms. Since late April 2020, reports regarding Kawasaki-like syndrome and hyperinflammatory response in children associated with COVID-19 have rapidly emerged. Till now, no certain relationship between multisystem inflammatory syndrome in Children (MIS-C) and Kawasaki Disease (KD) has been determined, which should be explored through continuous study. Methods: In order to synthesize key findings for the objectives of this review, we searched English literature published up to November 16, 2020 using PubMed with the following keywords: Kawasaki disease 2020, Kawasaki-like disease, MIS-C, PIMS, PMIS and PIMS-TS. Key Content and Findings: Based on current researches, KD is regarded as an immune disorder induced by multiple unidentified pathogens, while MIS-C is confirmed to be associated with the infection of COVID-19. In addition, KD is popular in East Asian children under 3 years old, while MIS-C is reported more in older adolescents from Europe and North America. On the basis of multiple cohort studies, gastrointestinal symptoms, mechanical ventilation and inotropic support are more common in MIS-C. Instead, coronary arterial damage is more pronounced in KD. Moreover, the treatment regimen for MIS-C is more aggressive than KD because the cytokine storm is more violent and lasting. Conclusions: MIS-C is likely to be a distinct immunopathogenic illness associated with SARS-CoV-2 based on current studies, which could be used as a reference to help us better understand KD. In addition, MIS-C is an emerging syndrome for pediatricians, so the lack of relevant knowledge may result in under-diagnosis. Some individuals may fulfill full or partial criteria for KD but all should be reported if they meet the case definition for MIS-C. © 2022 AME Publishing Company. All right reserved.

16.
Front Pediatr ; 10: 849473, 2022.
Article in English | MEDLINE | ID: covidwho-1775741

ABSTRACT

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare febrile disorder with multisystem organ involvement temporally associated with coronavirus 2019 infection (COVID-19) and frequently exhibits features mimicking Kawasaki disease (KD), another febrile disorder in children. The pathogenesis and the full clinical spectrum of MIS-C is poorly understood: It is still unclear whether MIS-C and KD are different syndromes or represent a common spectrum. The erythema and induration of Bacillus Calmette-Guérin (BCG) scar is one of the characteristic findings of KD, and is useful for the diagnosis in countries where BCG vaccination is mandated in infancy. Furthermore, such findings in BCG scar were also reported after SARS-CoV-2 vaccination, which may be related to molecular mimicry. However, there are no reports of changes at the BCG scar in MIS-C cases. Here, we report a case of MIS-C in a 3-year-old Hispanic boy in Japan, with erythema and induration at the BCG scar. The patient received BCG vaccination at 16 months of age in Japan. Four weeks before the onset, he had positive polymerase chain reaction (PCR) results for SARS-CoV-2 following household outbreak, although he was asymptomatic. He presented with fever and gastrointestinal symptoms, followed by the appearance of all six principal findings of complete KD. He exhibited congestive heart failure, following intravenous immunoglobulin (IVIG) therapy. He was diagnosed with MIS-C based on characteristic mucocutaneous and gastrointestinal symptoms, decreased cardiac function, and coagulopathy, in addition to laboratory data consistent with MIS-C. The BCG finding was present from the early stage of the disease. The patient was refractory to two doses of IVIGs, and the third IVIG plus prednisolone resulted in defervescence and improvement in heart failure. No coronary involvement was observed. This is the first case of erythema and induration at the BCG scar associated with MIS-C accompanied by KD features, which may give clinical and mechanistic insights in the understanding of the disease. Since the full spectrum of MIS-C is still evolving and both of them are syndromes with overlapped clinical features, further studies are warranted for deep phenotyping of MIS-C with KD features relative to KD in countries with mandatory BCG programs in infancy.

17.
Archives of Pediatric Infectious Diseases ; 10:6, 2022.
Article in English | Web of Science | ID: covidwho-1771669

ABSTRACT

Introduction: Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak, it was assumed that infection rate in pediatric patients is lower than in adults and that infection is less severe in children than adult patients. Recently, there have been several reports and case series presenting critically-ill children with COVID-19, but still, severe hypotension is rare in pediatric patients with COVID-19. Case Presentation: We describe three pediatric cases with COVID-19 who presented with multi-system organ failure and severe hypotension treated with the guidance of the parameters of an invasive continuous hemodynamic monitoring device. We also compare their parameters with few articles on pediatric sepsis parameters. Conclusions: Although we usually start the treatment of hypotensive pediatric patients with hydration and epinephrine as an inotrope, in our cases, we required a different treatment plan according to the hemodynamic monitoring parameters, which indicates the value of the utilization of these devices in pediatric intensive care units

18.
J Clin Med ; 11(6)2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1765752

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the outcomes of patients with the multisystem inflammatory syndrome in children (MIS-C) according to phenotypes of disease and define the prognostic factors for the severe course. METHODS: This cross-sectional study included 293 patients with MIS-C from seven pediatric rheumatology centers. A two-step cluster analysis was performed to define the spectrum of disease and their outcomes were compared between each group. RESULTS: Four subgroups were identified as follows: cluster I, predominantly Kawasaki-like features (n = 100); cluster II, predominantly MAS-like features (n = 34); cluster III, predominantly LV dysfunction (n = 47); cluster IV, other presentations (n = 112). The duration of fever was longer in cluster II and the length of hospitalization was longer in both clusters II and III. Laboratory findings revealed lower lymphocyte and platelet counts and higher acute phase reactants (APRs) in cluster II, while patients in cluster IV showed less inflammation with lower APRs. The resolution of abnormal laboratory findings was longer in clusters II and III, while it was shortest in cluster IV. Seven patients died. Among them, four belonged to cluster II, while three were labeled as cluster III. Patients with severe course had higher levels of neutrophil-lymphocyte ratio, mean platelet volume, procalcitonin, ferritin, interleukin-6, fibrinogen, D-Dimer, BNP, and troponin-I, and lower levels of lymphocyte and platelet counts. CONCLUSION: As shown, MIS-C is not a single disease presenting with various clinical features and outcomes. Understanding the disease spectrum will provide individualized management.

19.
Curr Allergy Asthma Rep ; 22(5): 53-60, 2022 05.
Article in English | MEDLINE | ID: covidwho-1750837

ABSTRACT

PURPOSE OF REVIEW: The novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has developed into a pandemic. A unique challenge of this pandemic has been the emergence of multisystem inflammatory syndrome in children (MIS-C), a rare post-infectious hyperinflammatory disorder associated with SARS-CoV-2. This syndrome is characterized by overwhelming systemic inflammation, fever, hypotension, and cardiac dysfunction. This disorder may also have features overlapping with Kawasaki disease (KD), macrophage activation syndrome (MAS), and toxic shock syndrome (TSS). The goal of this review is to outline the presenting features, presumed immunopathogenesis, management, and outcomes of patients with MIS-C. RECENT FINDINGS: Patients with MIS-C present with characteristics that fall within a wide clinical spectrum. Main features include fever, gastrointestinal symptoms such as abdominal pain and diarrhea, and cardiac complications such as myocarditis and coronary artery aneurysms, although various other features have been reported. Younger children may present with features of Kawasaki-like disease, and older children are often admitted to the intensive care unit with cardiogenic shock. Current treatment guidelines recommend intravenous immunoglobulins (IVIG) and glucocorticoids, with utilization of biologics in refractory cases. Fortunately, the majority of patients recover, with resolution of the systemic inflammation and cardiac abnormalities. Mortality from MIS-C is rare. This review provides an overview of the presenting features, proposed pathogenesis, suggested therapies, and outcomes of MIS-C. Clinicians must have a high clinical suspicion for this disorder in children who have had recent COVID-19 infection or exposure and present with a significant inflammatory response. Understanding of this disorder continues to evolve, and prompt diagnosis and treatment allow for the best possible outcome for patients with MIS-C.


Subject(s)
COVID-19 , Adolescent , COVID-19/complications , COVID-19/therapy , Child , Humans , Pandemics , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/complications , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/therapy
20.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-330028

ABSTRACT

Background: Multisystem inflammatory syndrome in children (MIS-C) occurs after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MIS-C hospitalizations depends on the risk of MIS-C following specific SARS-CoV-2 variants and vaccine effectiveness. Methods: This prospective nationwide multicentre cohort study included patients aged 0-17 years in Denmark with MIS-C following the SARS-CoV-2 variant Delta in the period August 1, 2021 to February 1, 2022. The risk of MIS-C was calculated using estimated number of infected individuals by vaccination status. We calculated the incidence rate of MIS-C per 1,000,000 vaccinated and unvaccinated person-years and estimated vaccine effectiveness as 1-IRR (incidence rate ratio) using Poisson regression. Phenotype and risk of MIS-C were compared with MIS-C cases from the first year of the pandemic. Findings: We identified fifty-one MIS-C cases among unvaccinated individuals and one in a fully vaccinated adolescent. The risk of MIS-C was one in 4,000 [95% CI 3,100-5,400] unvaccinated individuals with SARS-CoV-2 variant Delta and one in 15,800 [95% CI 2,800-500,000] vaccinated adolescents with break-through infections. The estimated vaccine effectiveness against MIS-C following the Delta variant was 94% [95% CI;55%-99%];p=0·005) in persons aged 5-17 years. The clinical phenotype during the Delta wave was comparable to the pre-Delta era, e.g. hypotension in 57% vs. 50%, respectively. Interpretation: We found the phenotype and the risk of MIS-C following infection with the Delta variant similar to previous variants. Further, we found a high vaccine effectiveness against MIS-C, which we suggest was due to protection from infection and, possibly, a decreased risk of MIS-C following break-through infection. Knowledge of the risk of MIS-C following different SARS-CoV-2 variants, and the effect of vaccination, is important for estimating MIS-C hospitalizations with new variants, such as Omicron, and in the debate of COVID-19 vaccination of children.

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