How we approach thrombosis risk in children with COVID-19 infection and MIS-C.
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ABSTRACT:
SUBMITTER: Sharathkumar AA
PROVIDER: S-EPMC8206673 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with thrombotic complications in adults, but the incidence of COVID-19-related thrombosis in children and adolescents is unclear. Most children with acute COVID-19 have mild disease, but coagulopathy has been associated with multisystem inflammatory syndrome in children (MIS-C), a postinfectious complication. We conducted a multicenter retrospective cohort study to determine the incidence of thrombosis in children hospitalized with COVID-19 or MIS-C and evaluate associated risk factors. We classified patients into 1 of 3 groups for analysis: COVID-19, MIS-C, or asymptomatic SARS-CoV-2. Among a total of 853 admissions (COVID-19, n = 426; MIS-C, n = 138; and asymptomatic SARS-CoV-2, n = 289) in 814 patients, there were 20 patients with thrombotic events (TEs; including 1 stroke). Patients with MIS-C had the highest incidence (9 [6.5%] of 138) vs COVID-19 (9 [2.1%] of 426) or asymptomatic SARS-CoV-2 (2 [0.7%] of 289). In patients with COVID-19 or MIS-C, a majority of TEs (89%) occurred in patients age ≥12 years. Patients age ≥12 years with MIS-C had the highest rate of thrombosis at 19% (9 of 48). Notably, 71% of TEs that were not present on admission occurred despite thromboprophylaxis. Multivariable analysis identified the following as significantly associated with thrombosis: age ≥12 years, cancer, presence of a central venous catheter, and MIS-C. In patients with COVID-19 or MIS-C, hospital mortality was 2.3% (13 of 564), but it was 28% (5 of 18) in patients with TEs. Our findings may help inform pediatric thromboprophylaxis strategies.
| S-EPMC8079262 | biostudies-literature
Project description:Background: COVID-19 has infected more than 100-million worldwide. Children appear less susceptible to COVID-19 and present with milder symptoms. Cases of children with COVID-19 developing clinical features of Kawasaki-disease have been described. Methods: We utilised SWATH-MS proteomics to determine the plasma proteins expressed in healthy children, children with multisystem inflammatory syndrome (MIS-C) and children with COVID-19 induced ARDS. Pathway analyses were performed to determine the affected pathways. Results: 76 proteins were differentially expressed across the groups, with 85 and 52 proteins specific to MIS-C and COVID-19 ARDS. Complement and coagulation activation were implicated in these clinical phenotypes, however there was contribution of FcGR and BCR activation in MIS-C and scavenging of heme and retinoid metabolism in COVID-19 ARDS. Conclusions: We show proteome differences in MIS-C and COVID-ARDS, although both show complement and coagulation dysregulation. The results may be helpful in developing therapeutic targets that could improve the outcomes for these children.
2022-04-06 | PXD025125 | Pride
Project description:BackgroundInfection by the 2019 novel coronavirus (COVID-19) has been reportedly associated with a high risk of thrombotic complications. So far information is scarce and rapidly emerging.MethodsWe conducted a scoping review using a single engine search for studies assessing thrombosis and coagulopathy in COVID-19 patients. Additional studies were identified by secondary review and alert services.ResultsStudies reported the occurrence of venous thromboembolism and stroke in approximately 20% and 3% of patients, respectively. A higher frequency seems to be present in severely ill patients, in particular those admitted to intensive care units. The thrombotic risk is elevated despite the use of anticoagulant prophylaxis but optimal doses of anticoagulation are not yet defined. Although an increase of biomarkers such as D-dimer has been consistently reported in severely ill COVID-19, the optimal cut-off level and prognostic value are not known.DiscussionA number of pressing issues were identified by this review, including defining the true incidence of VTE in COVID patients, developing algorithms to identify those susceptible to develop thrombotic complications and severe disease, determining the role of biomarkers and/or scoring systems to stratify patients' risk, designing adequate and feasible diagnostic protocols for PE, establishing the optimal thromboprophylaxis strategy, and developing uniform diagnostic and reporting criteria.
| S-EPMC7255332 | biostudies-literature
Project description:While SARS-CoV-2 infection results in a mild disease course for most children, severe manifestations including respiratory failure and a Multisystem Inflammatory Syndrome in Children (MIS-C) can develop in rare cases. Here, we present a longitudinal immune profiling study of children who developed SARS-CoV-2-associated MIS-C during acute disease and following recovery, relative to children with more typical clinical manifestations of SARS-CoV-2 infection. We demonstrate distinct immune parameters associated with acute MIS-C including elevated levels of pro-inflammatory cytokines in circulation not observed in children with acute COVID-19 (non-MIS-C), aberrant expression of activation and tissue residency signatures by T cells, and expansion of T cells bearing specific TCR chains. Importantly, markers of tissue-derived T cells correlated with clinical measurements of cardiac damage suggesting key roles for T cells in the disease process. While these T cell alterations and the accompanying systemic inflammation resolved during recovery, children with prior MIS-C generated increased frequencies of functionally robust virus-specific T cells compared to children who recovered from mild disease, while both cohorts generated protective, long-lasting SARS-CoV-2-specific antibodies. Together our results reveal that the T cell response in acute MIS-C contributed to disease pathology, while also generating robust memory responses for future immune protection.
2023-04-10 | GSE213192 | GEO
Project description: Not available
| S-BSST563 | biostudies-other
Project description:Multisystem inflammatory syndrome in children (MIS-C) is an inflammatory condition associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is characterized by fever, gastro-intestinal symptoms, cardiovascular complications, conjunctivitis, skin involvement, elevated inflammatory markers, and coagulation abnormalities. The current ongoing COVID-19 pandemic causes an increased alertness to MIS-C. In combination with the heterogeneous clinical spectrum, this could potentially lead to diagnostic blindness, misdiagnosis of MIS-C, and overtreatment with expensive IVIG treatment. This report demonstrates the challenge of accurately distinguishing MIS-C from other more common inflammatory pediatric diseases, and the need to act with caution to avoid misdiagnoses in the current pandemic. We present a case series of 11 patients suspected of MIS-C based on the current definitions. Three of them were eventually diagnosed with a different disease.ConclusionCurrent definitions and diagnostic criteria lack specificity which potentially leads to misdiagnosis and overtreatment of MIS-C. We emphasize the need to act with caution in order to avoid MIS(-C)-taken diagnoses in the current pandemic.What is known• A pediatric multisystem inflammatory disease associated with SARS-CoV-2 has been described (MIS-C). • There are three definitions being used for MIS-C, all including fever for at least 24 h, laboratory evidence of inflammation, clinically severe illness with multi-organ (≥ 2) involvement, and no alternative plausible diagnosis.What is new• MIS-C has a heterogeneous clinical spectrum without distinctive features compared to more common childhood diseases. Current definitions and diagnostic criteria for MIS-C lack specificity which leads to misdiagnosis and overtreatment. • Amid the current excessive attention to COVID-19 and MIS-C, pediatricians should remain vigilant to avoid mistaken diagnoses.
| S-EPMC9302213 | biostudies-literature
Project description:ObjectiveTo identify risk factors for persistent impairments after pediatric hospitalization for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic.MethodsAcross 25 U.S. Overcoming COVID-19 Network hospitals, we conducted a prospective cohort study of patients <21-years-old hospitalized for acute COVID-19 or MIS-C (May 2020 to March 2022) surveyed 2- to 4-months post-admission. Multivariable regression was used to calculate adjusted risk ratios (aRR) and 95% confidence intervals (CI).ResultsOf 232 children with acute COVID-19, 71 (30.6%) had persistent symptoms and 50 (21.6%) had activity impairments at follow-up; for MIS-C (n = 241), 56 (23.2%) had persistent symptoms and 58 (24.1%) had activity impairments. In adjusted analyses of patients with acute COVID-19, receipt of mechanical ventilation was associated with persistent symptoms [aRR 1.83 (95% CI: 1.07, 3.13)] whereas obesity [aRR 2.18 (95% CI: 1.05, 4.51)] and greater organ system involvement [aRR 1.35 (95% CI: 1.13, 1.61)] were associated with activity impairment. For patients with MIS-C, having a pre-existing respiratory condition was associated with persistent symptoms [aRR 3.04 (95% CI: 1.70, 5.41)] whereas obesity [aRR 1.86 (95% CI: 1.09, 3.15)] and greater organ system involvement [aRR 1.26 (1.00, 1.58)] were associated with activity impairments.DiscussionAmong patients hospitalized, nearly one in three hospitalized with acute COVID-19 and one in four hospitalized with MIS-C had persistent impairments for ≥2 months post-hospitalization. Persistent impairments were associated with more severe illness and underlying health conditions, identifying populations to target for follow-up.
| S-EPMC10619659 | biostudies-literature
Project description:In early 2020, at the beginning of the coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare cases were reported in children and adolescents of multisystem inflammatory syndrome in children (MIS-C). MIS-C is characterized by fever, systemic inflammation, and multiorgan dysfunction and usually presents late in SARS-CoV-2 infection. Since May 2020, the Centers for Disease Control and Prevention (CDC) has recorded all reported cases of COVID-19 and MIS-C in children and adolescents in the USA. In April 2021, the American College of Rheumatology (ACR) revised its clinical guidelines for diagnosing and managing hyperinflammation and MIS-C. There are several challenges ahead for preventing, diagnosing, and managing MIS-C, particularly following the rapid emergence of new strains of SARS-CoV-2. This Editorial aims to present an update on the current status of the clinical presentation, diagnosis, and management of MIS-C and includes some updates from population studies and clinical guidelines.
| S-EPMC8176784 | biostudies-literature
Project description: Not available
| S-EPMC7229939 | biostudies-literature
Project description:Purpose: This study aims to characterize the early innate and adaptive responses induced by SARS-CoV-2 infection in children and adults over time up to 8 weeks post symptoms onset (POS). We report the gene signature of COVID-19 over the course of the disease in both age groups. The kinetic of infection was divided in 5-time intervals according to the calculated days POS: interval 1 (0-5), interval 2 (6-14), interval 3 (15-22), interval 4 (23-35), and interval 5 (36-81). Methods: RNA extraction was performed automatically via the PAXgene Blood miRNA Kit and the QIAcube instrument (Qiagen) following the manufacturer’s protocol. RNA concentration and quality were assessed by using the Qubit instrument (Invitrogen) and the Agilent 2100 Bioanalyzer, respectively. The Stranded Total RNA Ribo-Zero Plus kit from Illumina was used for the library preparation with 100 ng of total RNA as input. Library molarity and quality were assessed with the Qubit and Tapestation using a DNA High sensitivity chip (Agilent Technologies). Libraries were pooled at 2 nM for clustering and sequenced on an Illumina HiSeq 4000 sequencer for a minimum of 30 million single-end 100 reads per sample. Main results: (I) we observed an antiviral-IFN-signature and innate-cell-activation within the first 5 days post symptoms onset (POS), while genes associated with CD4 T-cell responses, plasma cells and immunoglobulin were upregulated in both age groups during the first two weeks POS, indicative of SARS-CoV-2-specific adaptive immune responses; (II) in adults, genes associated with IFN antiviral responses and activated dendritic cells were maintained during the second week of disease, and subsided only after 14 days. By contrast, those transcriptome changes subsided already after 5 days in children.
2021-09-22 | GSE166190 | GEO