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MeSH Disease

Human Phenotype

Transmission

Seroprevalence

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    COVID-19 and Children TRANS With Down Syndrome MESHD: is There Any Real Reason to Worry? Case Report

    Authors: Ahmad Kantar; Angelo Mazza; Ezio Bonanomi; Marta Odoni; Manuela Seminara; Ilaria Dalla Verde; Camillo Lovati; Stefania Bolognini; Lorenzo D’Antiga

    doi:10.21203/rs.3.rs-44432/v1 Date: 2020-07-16 Source: ResearchSquare

    Background: Down syndrome MESHD (DS) is characterised by a series of immune dysregulations HP, of which interferon hyperreactivity is a key one as it is responsible for surging antiviral responses and probable initiation of an amplified cytokine storm. This biological condition is attributed to immune regulators encoded in chromosome 21. Moreover, DS is characterised by the coexistence of cardiovascular and respiratory anomalies as well as obesity MESHD obesity HP, which constitutes a risk factor for SARS-CoV-2 respiratory disease MESHD (COVID-19).Case presentation: Of the total number of children 55 admitted to paediatric wards in Bergamo in the period between February to May 2020 for COVID-19 infection MESHD, we present 2 children TRANS with DS and confirmed COVID-19 diagnosis that had a severe course. In addition, both cases had one or more comorbidities, being cardiovascular anomalies, obesity MESHD obesity HP, and/or OSA.Conclusions: Our observations indicate the need to consider children TRANS with DS a population at a risk of severe COVID-19.

    Network analysis of Down syndrome MESHD and SARS-CoV-2 identifies risk and protective factors for COVID-19

    Authors: Ilario De Toma; Mara Dierssen

    doi:10.21203/rs.3.rs-34625/v1 Date: 2020-06-11 Source: ResearchSquare

    Background: SARS-CoV-2 has spread uncontrollably worldwide while we still ignore how particularly vulnerable populations, such as Down syndrome MESHD (DS) individuals are affected by the COVID-19 pandemic. Individuals with DS have more risk of infections TRANS risk of infections TRANS infections MESHD with respiratory complications and present signs of auto- inflammation MESHD. They also suffer from multiple comorbidities that are associated with poorer COVID-19 prognosis in the general population. All this might place DS individuals at higher risk of SARS-CoV-2 infection MESHD or poorer clinical outcomes.Methods: In order to get insight into the interplay between DS genes and SARS-cov2 infection MESHD and pathogenesis we retrieved the genes belonging to the molecular pathways involved in COVID-19 and the host proteins interacting with viral proteins from SARS-CoV-2. We therefore analyzed the overlaps of these genes with HSA21 genes, HSA21 interactors and other genes consistently differentially expressed in DS (using public transcriptomic datasets) creating a DS-SARS-CoV-2 network.Results: We detected COVID-19 protective and risk factors that might affect the susceptibility of individuals with DS both at the infection MESHD stage and in the progression to acute respiratory distress HP syndrome MESHD.Conclusion: Our analysis suggests that at the infection MESHD stage DS individuals might be more susceptible to infection MESHD due to triplication of TMPRSS2, that primes the viral S protein for entry in the host cells, even though the anti-viral interferon I signaling is upregulated in DS and this might increase the initial anti-viral response. In the second pro-inflammatory immunopathogenic phase of the infection MESHD, the prognosis for DS patients might worsen due to upregulation of inflammatory genes that might favor the typical cytokine storm of COVID-19. We also detected strong downregulation of the NLRP3 gene, critical for maintenance of homeostasis against pathogenic infections MESHD, possibly leading to bacterial infection MESHD complications.

    COVID-19 Hospitalization is More Frequent and Severe in Down Syndrome MESHD

    Authors: Louise Malle; Cynthia Gao; Nicole Bouvier; Bethany Percha; Dusan Bogunovic

    doi:10.1101/2020.05.26.20112748 Date: 2020-06-02 Source: medRxiv

    Background. Individuals with rare disorders, like Down syndrome MESHD (DS) are historically understudied. Currently, it is not known how COVID-19 pandemic affects individuals with DS. Herein, we report an analysis of individuals with DS who were hospitalized with COVID-19 in the Mount Sinai Health System in New York City, USA. Methods. In this retrospective, single-center study of 4,615 patients hospitalized with COVID-19, we analyzed all patients with DS admitted in the Mount Sinai Health System. Hospitalization rates, clinical and outcomes were assessed. Findings. Contrary to an expected number of one, we identified six patients with DS. We found that patients with DS are at an 8.9-fold higher risk of hospitalization with COVID-19 when compared to non-DS patients. Hospitalized DS individuals are on average 10 years younger than non-DS patients with COVID-19. Moreover, type 2 diabetes mellitus MESHD diabetes mellitus HP appears to be an important driver of this susceptibility to COVID-19. Finally, patients with DS have more severe outcomes than controls, and are more likely to progress to sepsis MESHD sepsis HP in particular. Interpretation. We demonstrate that individuals with DS represent a higher risk population for COVID-19 compared to the general population and conclude that particular care should be taken for both the prevention and treatment of COVID-19 in these patients. Funding. National Institute of Allergy HP and Infectious Diseases MESHD

    JAK1 inhibition blocks lethal sterile immune responses:implications for COVID-19 therapy

    Authors: Kathryn Tuttle; Ross Minter; Katherine Waugh; Paula Araya; Michael Ludwig; Colin Sempeck; Keith Smith; Zdenek Andrysik; Matthew Burchill; Beth Tamburini; David Orlicky; Kelly D Sullivan; Joaquin Espinosa

    doi:10.1101/2020.04.07.024455 Date: 2020-04-09 Source: bioRxiv

    Cytokine storms are drivers of pathology and mortality in myriad viral infections MESHD affecting the human population. In SARS-CoV-2-infected patients, the strength of the cytokine storm has been associated with increased risk of acute respiratory distress HP syndrome MESHD, myocardial damage, and death MESHD. However, the therapeutic value of attenuating the cytokine storm in COVID-19 remains to be defined. Here, we report results obtained using a novel mouse model of lethal sterile anti-viral immune responses. Using a mouse model of Down syndrome MESHD (DS) with a segmental duplication of a genomic region encoding four of the six interferon receptor genes (Ifnrs), we demonstrate that these animals overexpress Ifnrs and are hypersensitive to IFN stimulation. When challenged with viral mimetics that activate Toll-like receptor signaling and IFN anti-viral responses, these animals overproduce key cytokines, show exacerbated liver pathology, rapidly lose weight, and die. Importantly, the lethal immune hypersensitivity MESHD, accompanying cytokine storm, and liver hyperinflammation are blocked by treatment with a JAK1-specific inhibitor. Therefore, these results point to JAK1 inhibition as a potential strategy for attenuating the cytokine storm and consequent organ failure during overdrive immune responses. Additionally, these results indicate that people with DS, who carry an extra copy of the IFNR gene cluster encoded on chromosome 21, should be considered at high risk during the COVID-19 pandemic. One Sentence SummaryInhibition of the JAK1 kinase prevents pathology and mortality caused by a rampant innate immune response in mice.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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