Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS CoV-2
JOURNAL OF CLINICAL INVESTIGATION
Authors: Diorio, Caroline; Henrickson, Sarah E.; Vella, Laura A.; McNerney, Kevin O.; Chase, Julie; Burudpakdee, Chakkapong; Lee, Jessica H.; Jasen, Cristina; Balamuth, Fran; Barrett, David M.; Banwell, Brenda L.; Bernt, Kathrin M.; Blatz, Allison M.; Chiotos, Kathleen; Fisher, Brian T.; Fitzgerald, Julie C.; Gerber, Jeffrey S.; Gollomp, Kandace; Gray, Christopher; Grupp, Stephan A.; Harris, Rebecca M.; Kilbaugh, Todd J.; John, Audrey R. Odom; Lambert, Michele; Liebling, Emily J.; Paessler, Michele E.; Petrosa, Whitney; Phillips, Charles; Reilly, Anne F.; Romberg, Neil D.; Seif, Alix; Sesok-Pizzini, Deborah A.; Sullivan, Kathleen E.; Vardaro, Julie; Behrens, Edward M.; Teachey, David T.; Bassiri, Hamid
Abstract
BACKGROUND. Initial reports from the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology. METHODS. We prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data. RESULTS. Twenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines IL-10. IL-6, IL-8, and TNF-alpha) contributed to the analysis. TNF-alpha and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C. CONCLUSION. Pediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19.
Butyrate mediates anti-inflammatory effects ofFaecalibacterium prausnitziiin intestinal epithelial cells throughDact3
GUT MICROBES
Authors: Lenoir, Marion; Martin, Rebeca; Torres-Maravilla, Edgar; Chadi, Sead; Gonzalez-Davila, Pamela; Sokol, Harry; Langella, Philippe; Chain, Florian; Bermudez-Humaran, Luis G.
Abstract
The commensal bacteriumFaecalibacterium prausnitziiplays a key role in inflammatory bowel disease (IBD) pathogenesis and serves as a general health biomarker in humans. However, the host molecular mechanisms that underlie its anti-inflammatory effects remain unknown. In this study we performed a transcriptomic approach on human intestinal epithelial cells (HT-29) stimulated with TNF-alpha and exposed toF. prausnitziiculture supernatant (SN) in order to determine the impact of this commensal bacterium on intestinal epithelial cells. Moreover, modulation of the most upregulated gene afterF. prausnitziiSN contact was validated bothin vitroandin vivo. Our results showed thatF. prausnitziiSN upregulates the expression ofDact3, a gene linked to the Wnt/JNK pathway. Interestingly, when we silencedDact3expression, the effect ofF. prausnitziiSN was lost. Butyrate was identified as theF. prausnitziieffector responsible forDact3modulation.Dact3upregulation was also validatedin vivoin both healthy and inflamed mice treated with eitherF. prausnitziiSN or the live bacteria, respectively. Finally, we demonstrated by colon transcriptomics that gut microbiota directly influencesDact3expression. This study provides new clues about the host molecular mechanisms involved in the anti-inflammatory effects of the beneficial commensal bacteriumF. prausnitzii.
COA
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