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

Language
en
Document Type
Article
Issue Date
2023-03-28
First published
2021-12-10
Issue Year
2021
Authors
Ruhl, Louisa
Pink, Isabell
Kühne, Jenny F.
Beushausen, Kerstin
Keil, Jana
Christoph, Stella
Sauer, Andrea
Boblitz, Lennart
Schmidt, Julius
David, Sascha
Editor
Publisher
Nature Publishing Group UK
Abstract

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 infection. To define hallmarks of severe COVID-19 in acute disease (n = 58) and in disease recovery in convalescent patients (n = 28) from Hannover Medical School, we used flow cytometry and proteomics data with unsupervised clustering analyses. In our observational study, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU 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 antibodies. The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In 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.

Journal Title
Signal Transduction and Targeted Therapy
Volume
6
Issue
1
Citation
Signal Transduction and Targeted Therapy 6 (2021): 418. <https://www.nature.com/articles/s41392-021-00819-6>
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