Browse
Submit Data
Databases
API
Help

Dataset Information

18 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Atypical Inflammatory Syndrome Triggered by SARS-CoV-2 in Infants with Down Syndrome.

ABSTRACT: While adults with Down syndrome (DS) are at increased risk of severe COVID-19 pneumonia, little is known about COVID-19 in children with DS. In children without DS, SARS-CoV-2 can rarely cause severe COVID-19 pneumonia, or an even rarer and more typically pediatric condition, multisystem inflammatory syndrome in children (MIS-C). Although the underlying mechanisms are still unknown, MIS-C is thought to be primarily immune-mediated. Here, we describe an atypical, severe form of MIS-C in two infant girls with DS who were hospitalized for over 4 months. Immunological evaluation revealed pronounced neutrophilia, B cell depletion, increased circulating IL-6 and IL-8, and elevated markers of immune activation ICAM1 and FcɣRI. Importantly, uninfected children with DS presented with similar but less stark immune features at steady state, possibly explaining risk of further uncontrolled inflammation following SARS-CoV-2 infection. Overall, a severe, atypical form of MIS-C may occur in children with DS.

SUBMITTER: Malle L

PROVIDER: S-EPMC8178650 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Atypical hemolytic uremic syndrome triggered by mRNA vaccination against SARS-CoV-2: Case report.

Project description:Atypical hemolytic uremic syndrome (aHUS), also called complement-mediated hemolytic uremic syndrome (CM-HUS), is a rare disease caused by dysregulation in the alternative complement activation pathway. It is a life-threatening condition causing ischemia of a number of organs, and it typically causes acute kidney injury. This disorder may be triggered by various factors including viral or bacterial infections, pregnancy, surgery, and injuries. In about 60% of cases, the genetic origin of the disease can be identified-commonly mutations affecting complementary factor H and MCP protein. Eculizumab, a monoclonal antibody to the C5 component of the complement, represents the current effective treatment.We describe a case of a young woman with a previous history of polyvalent allergies, who developed atypical hemolytic uremic syndrome after vaccination with mRNA vaccine against SARS-CoV-2. The disease manifested by scleral bleeding, acute renal insufficiency, anemia, and thrombocytopenia. The patient was treated with plasma exchanges without sufficient effect; remission occurred only after starting treatment with eculizumab. Genetic examination showed that the patient is a carrier of multiple inherited risk factors (a rare pathogenic variant in CFH, MCPggaac haplotype of the CD46 gene, and the risk haplotype CFH H3). The patient is currently in hematological remission with persistent mild renal insufficiency, continuing treatment with eculizumab/ravulizumab. By this case report, we meant to point out the need for careful monitoring of people after vaccination, as it may trigger immune-mediated diseases, especially in those with predisposing factors.

| S-EPMC9580272 | biostudies-literature

Atypical Hemolytic and Uremic Syndrome Triggered by Infection With SARS-CoV2.

Project description: Not available

| S-EPMC8265210 | biostudies-literature

Eculizumab, SARS-CoV-2 and atypical hemolytic uremic syndrome.

Project description:Atypical hemolytic uremic syndrome (aHUS) treatment consists of eculizumab. Severe acute respiratory syndrome coronavirus 2 causes severe pneumonia and endothelial injury that leads to a prothrombotic state that may be complicated by macrovascular and microvascular thrombosis. Complement activation is thought to contribute to endothelial injury and there are at least seven ongoing clinical trials testing six different anti-complement strategies for coronavirus disease 2019 (COVID-19), including eculizumab. We herein report on a kidney transplant patient with aHUS on chronic eculizumab therapy that developed severe COVID-19 despite eculizumab administration early in the course of the disease. Although eculizumab was unable to prevent the development of severe endothelial cell injury, as assessed by increasing D-dimer levels from 292 to 10?586?ng/mL, the patient eventually recovered following dexamethasone and convalescent plasma administration.

| S-EPMC7543344 | biostudies-literature

Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies

Project description:Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here we uncover a role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.

| S-SCDT-10_1038-S44318-024-00061-0 | biostudies-other

Current Strategies in Treating Cytokine Release Syndrome Triggered by Coronavirus SARS-CoV-2.

Project description:Since the beginning of the SARS-CoV-2 pandemic, the treatments and management of the deadly COVID-19 disease have made great progress. The strategies for developing novel treatments against COVID-19 include antiviral small molecule drugs, cell and gene therapies, immunomodulators, neutralizing antibodies, and combination therapies. Among them, immunomodulators are the most studied treatments. The small molecule antiviral drugs and immunoregulators are expected to be effective against viral variants of SARS-CoV-2 as these drugs target either conservative parts of the virus or common pathways of inflammation. Although the immunoregulators have shown benefits in reducing mortality of cytokine release syndrome (CRS) triggered by SARS-CoV-2 infections, extensive investigations on this class of treatment to launch novel therapies that substantially improve efficacy and reduce side effects are still warranted. Moreover, great challenges have emerged as the SARS-CoV-2 virus quickly, frequently, and continuously evolved. This review provides an update and summarizes the recent advances in the treatment of COVID-19 and in particular emphasized the strategies in managing CRS triggered by SARS-CoV-2. A brief perspective in the battle against the deadly disease was also provided.

| S-EPMC9124488 | biostudies-literature

[Multisystem inflammatory syndrome in adults associated to SARS-CoV-2].

Project description: Not available

| S-EPMC8647029 | biostudies-literature

Multisystem inflammatory syndrome in adults associated to SARS-CoV-2.

Project description: Not available

| S-EPMC9058030 | biostudies-literature

SARS-CoV-2 Variants and Multisystem Inflammatory Syndrome in Children.

Project description: Not available

| S-EPMC10052214 | biostudies-literature

Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2

Project description:Why individuals with Down Syndrome (DS, trisomy 21) are particularly susceptible to SARS-CoV-2 induced disease remains largely unclear. The choroid plexus secrets the cerebrospinal fluid and strongly expresses the ACE2 receptor and the chromosome 21 encoded TMPRSS2 protease. To investigate the role of the choroid plexus in SARS-CoV-2 central nervous system infection in DS, we established a new type of brain organoid from DS and isogenic euploid control iPSC that consists of a core of appropriately patterned functional cortical neuronal cell types that is surrounded by a patent and functional choroid plexus (CPCOs). Remarkably, DS-CPCOs not only recapitulated abnormal features of DS cortical development but also revealed defects in ciliogenesis and epithelial cell polarity of the developing choroid plexus. We next demonstrate that the choroid plexus layer facilitates SARS-CoV-2 replication and infection of cortical neuronal cells, and that this is increased in DS-CPCOs. We further show that inhibition of TMPRSS2 activity in DS-CPCOs inhibits SARS-CoV-2 infectivity. We conclude that CPCOs are a useful model for dissecting the role of the choroid plexus in euploid and DS forebrain development and enables screening for therapeutics that can inhibit SARS-CoV-2 induced neuro-pathogenesis.

2022-07-26 | GSE208575 | GEO

Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2

2023-10-16 | GSE208440 | GEO