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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

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    SARS-CoV-2 infects blood MESHD monocytes to activate NLRP3 HGNC and AIM2 HGNC inflammasomes, pyroptosis and cytokine release

    Authors: Caroline Junqueira; Angela Crespo; Shahin Ranjbar; Jacob Ingber; Blair Parry; Sagi David; Luna B de Lacerda; Mercedes Lewandrowski; Sarah Alden Clark; Felicia Ho; Setu Vora; Valerie Leger; Caroline Beackes; Justin Margolin; Nicole Russell; Lee Gehrke; Upasana Das Adhikari; Lauren Henderson; Erin Janssen; Douglas Kwon; Chris Sander; Jonathan Abraham; Michael Filbin; Marcia B. Goldberg; Hao Wu; Mehta Gautam; Steven Bell; Anne Goldfeld; Judy Lieberman

    doi:10.1101/2021.03.06.21252796 Date: 2021-03-08 Source: medRxiv

    SARS-CoV-2 causes acute respiratory distress that can progress to multiorgan failure MESHD and death MESHD in some patients. Although severe COVID-19 MESHD disease is linked to exuberant inflammation MESHD, how SARS-CoV-2 triggers inflammation MESHD is not understood. Monocytes are sentinel blood cells that sense invasive infection MESHD to form inflammasomes that activate caspase-1 HGNC and gasdermin D HGNC ( GSDMD HGNC GSDMD MESHD) pores, leading to inflammatory death MESHD (pyroptosis) and processing and release of IL-1 family cytokines, potent inflammatory mediators. Here we show that ~10% of blood monocytes in COVID-19 MESHD patients are dying and infected with SARS-CoV-2. Monocyte infection, which depends on antiviral antibodies, activates NLRP3 HGNC and AIM2 HGNC inflammasomes, caspase-1 HGNC and GSDMD HGNC cleavage and relocalization. Signs of pyroptosis (IL-1 family cytokines, LDH) in the plasma correlate with development of severe disease. Moreover, expression quantitative trait loci (eQTLs) linked to higher GSDMD HGNC expression increase the risk of severe COVID-19 MESHD disease (odds ratio, 1.3, p<0.005). These findings taken together suggest that antibody-mediated SARS-CoV-2 infection MESHD of monocytes triggers inflammation MESHD that contributes to severe COVID-19 MESHD disease pathogenesis.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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