Project description:BackgroundDuring the Coronavirus disease 2019 (COVID-19) pandemic, reports have emerged of a multisystem inflammatory syndrome in adults (MIS-A). Multisystem inflammatory syndrome in adults can affect various organ systems, including cardiovascular, gastrointestinal, and neurologic systems without significant respiratory involvement.Case summaryA previously healthy 43-year-old man presented with fevers and abdominal pain then rapidly deteriorated into cardiogenic shock. His constellation of symptoms along with elevated inflammatory markers in the setting of a recent SARS-CoV-2 infection was consistent with the diagnosis of MIS-A. He also had a comprehensive infectious workup that was unremarkable, ruling out other potential infectious aetiologies for his presentation. He subsequently improved through supportive measures and after administration of intravenous immunoglobulin (IVIG). He later demonstrated recovery of cardiac function and cardiac magnetic resonance imaging (MRI) showed signs consistent with myocarditis.DiscussionAs the COVID-19 pandemic continues to be an ongoing issue, it is important to recognize MIS-A, a rare and potentially deadly clinical syndrome that can lead to profound cardiovascular complications. Non-invasive imaging modalities such as cardiac MRI can play a role in the identification of myocarditis. In addition to supportive management, adjunctive therapies such as IVIG may be efficacious in MIS-A and should be further investigated.
Project description:BackgroundMultisystem Inflammatory Syndrome in Children (MIS-C) is a life-threatening complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which manifests as a hyper inflammatory process with multiorgan involvement in predominantly healthy children in the weeks following mild or asymptomatic coronavirus disease 2019 (COVID-19). However, host monogenic predisposing factors to MIS-C remain elusive.MethodsHerein, we used whole exome sequencing (WES) on 16 MIS-C Brazilian patients to identify single nucleotide/InDels variants as predisposition factors associated with MIS-C.ResultsWe identified ten very rare variants in eight genes (FREM1, MPO, POLG, C6, C9, ABCA4, ABCC6, and BSCL2) as the most promising candidates to be related to a higher risk of MIS-C development. These variants may propitiate a less effective immune response to infection or trigger the inflammatory response or yet a delayed hyperimmune response to SARS-CoV-2. Protein-Protein Interactions (PPIs) among the products of the mutated genes revealed an integrated network, enriched for immune and inflammatory response mechanisms with some of the direct partners representing gene products previously associated with MIS-C and Kawasaki disease (KD). In addition, the PPIs direct partners are also enriched for COVID-19-related gene sets. HLA alleles prediction from WES data allowed the identification of at least one risk allele in 100% of the MIS-C patients.ConclusionsThis study is the first to explore host MIS-C-associated variants in a Latin American admixed population. Besides expanding the spectrum of MIS-C-associated variants, our findings highlight the relevance of using WES for characterising the genetic interindividual variability associated with COVID-19 complications and ratify the presence of overlapping/convergent mechanisms among MIS-C, KD and COVID-19, crucial for future therapeutic management.
Project description:Adolescents with coronavirus disease 2019 (COVID-19) associated multisystem inflammatory syndrome (MIS) can present with shock and myocardial injury and mimic Kawasaki disease. We describe 4 previously well adolescents (age 13-14 years), presenting with clinical features of MIS in children (MIS-C). All patients had nearly similar clinical presentation. Hematological investigations revealed elevated inflammatory markers, anemia, thrombocytopenia, and decreased neutrophil:lymphocyte ratio. All patients were negative on real-time polymerase chain reaction against severe acute respiratory syndrome coronavirus 2, but had elevated immunoglobulin G titers. Two patients had atypical Kawasaki disease. Three patients had severe disease with hypotensive shock and required intensive care with fluids and inotropes. Two patients required non-invasive respiratory support for dyspnea and one patient had biventricular dysfunction. All received empiric antibiotics, low-molecular weight heparin, steroids, and intravenous immunoglobulin. One patient succumbed, while others recovered well. MIS-C may be a late presentation in adolescent with COVID-19. Individualized treatment with empiric antibiotics, immunomodulation, and thromboprophylaxis can result in significantly better outcome.
Project description:BackgroundMultisystem inflammatory syndrome in children (MIS-C) is a postinfectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complication that has disproportionately affected racial/ethnic minority children. We conducted a pilot study to investigate risk factors for MIS-C aiming to understand MIS-C disparities.MethodsThis case-control study included MIS-C cases and SARS-CoV-2-positive outpatient controls less than 18 years old frequency-matched 4:1 to cases by age group and site. Patients hospitalized with MIS-C were admitted between March 16 and October 2, 2020, across 17 pediatric hospitals. We evaluated race, ethnicity, social vulnerability index (SVI), insurance status, weight-for-age and underlying medical conditions as risk factors using mixed effects multivariable logistic regression.ResultsWe compared 241 MIS-C cases with 817 outpatient SARS-CoV-2-positive at-risk controls. Cases and controls had similar sex, age and U.S. census region distribution. MIS-C patients were more frequently previously healthy, non-Hispanic Black, residing in higher SVI areas, and in the 95th percentile or higher for weight-for-age. In the multivariable analysis, the likelihood of MIS-C was higher among non-Hispanic Black children [adjusted odds ratio (aOR): 2.07; 95% CI: 1.23-3.48]. Additionally, SVI in the 2nd and 3rd tertiles (aOR: 1.88; 95% CI: 1.18-2.97 and aOR: 2.03; 95% CI: 1.19-3.47, respectively) were independent factors along with being previously healthy (aOR: 1.64; 95% CI: 1.18-2.28).ConclusionsIn this study, non-Hispanic Black children were more likely to develop MIS-C after adjustment for sociodemographic factors, underlying medical conditions, and weight-for-age. Investigation of the potential contribution of immunologic, environmental, and other factors is warranted.
Project description:Multisystem inflammatory syndrome in children (MIS-C) can cause a myriad of cardiac manifestations, including coronary dilation and aneurysms; giant aneurysms are infrequent. We describe 3patients with giant coronary aneurysms associated with MIS-C, including the youngest case reported to date, treated with intravenous immunoglobulin, corticosteroids, and biologic agents. (Level of Difficulty: Intermediate.).
Project description:The use of electronic cigarettes (e-cigarettes) and vaping among adolescents has risen exponentially in the last decade. E-cigarette flavors has driven adolescents to use these convenient, USB-like devices, designed to create a desired social image, while being seemingly unaware of the serious health consequences of their behavior. Vaping impacts protective pulmonary barriers by attenuating the mucociliary clearance and by increasing peribronchial inflammation and fibrosis. The recent SARS-CoV-2 (COVID-19) pandemic has been characterized by a plethora of unusual disease presentations. Among them, a unique presentation seen exclusively in children and adolescents was multisystem inflammatory syndrome (MIS-C). Seventy percent of adolescents who had MIS-C also had acute respiratory distress syndrome (ARDS), and we speculate that there may exist common denominator that links MIS-C and adolescents: the use of e-cigarettes. The virus targets the angiotensin converting receptor (ACE receptor), and studies have shown nicotine-based e-cigarettes or vaping cause oxidative stress and resulting in the upregulation of ACE2, which might worsen ARDS in MIS-C. Our mini-review highlights that adolescents using e-cigarette have alterations in their pulmonary defenses against SARS-CoV-2: an upregulation of the ACE2 receptors, the primary target of SARS-CoV-2. Their compromised immune system makes them more uniquely vulnerable to Covid-19 related MIS-C, increasing their risk for ARDS and related morbidities. Currently, studies have shown an association between MIS-C and vaping, we speculate that adolescents who vape/smoke might be especially vulnerable to serious respiratory symptoms if they develop a hyper-inflammatory state MIS-C.