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Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks

引用

Signal Transduction and Targeted Therapy 2022年第1期7卷 243-257页

作者： Louisa Ruhl Isabell Pink jenny f.kiihne Kerstin Beushausen Jana Keil Stella Christoph Andrea Sauer Lennart Boblitz Julius Schmidt Sascha David Hans-Martin Jack Edith Roth Markus Cornberg Thomas f.Schulz Tobias Welte Marius M.Hoper Christine S.falk Institute of Transplant Immunology MHHDHanoverGermany Department of Pneumology MHHDHanoverGermany Department of Intensive Care Medicine University of ZurichCHZurichSwitzerland Division of Molecular Immunology Internal Medicine IIINikolaus-Fiebiger-Center of Molecular MedicineFriedrich-Alexander University Erlangen-NurnbergDErlangenGermany Department of Gastroenterology Hepatology and Endocrinology MHHDHanoverGermany Center for Individualized Infection Medicine CiiM HanoverGermany lnstitute of Virology MHHDHanoverGermany German Center for Infection Research DZIFTTU-IICHMarburgGermany Excellence Cluster 2155 RESIST MHHHanoverGermany German Center for Lung Diseases DZL/BREATH MarburgGermany

The systemic processes involved in the manifestation of life・threatening COVID-19 and in disease recovery are still incompletely understood,despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 *** define hallmarks of severe COVID-19 in acute disease(n=58)and in disease recovery in con valesce nt patie nts(n=28)from Han nover Medical School,we used flow cytometry and proteomics data with unsupervised clustering *** our observational study,we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and *** patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific *** core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe *** within this sign ature were associated with either disease progression or *** summary,our data suggest that besides a strong inflammatory response,severe COVID-19 is driven by endothelial activation and barrier disruption,whereby recovery depends on the regeneration of the endothelial integrity.

关键词： cytokine networks signature

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