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

Ruhl L, Pink I, Kuehne JF, Beushausen K, Keil J, Christoph S, Sauer A, Boblitz L, Schmidt J, David S, Jäck HM, Roth E, Cornberg M, Schulz TF, Welte T, Hoeper MM, Falk CS (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Signal Transduction and Targeted Therapy Springer Nature

Book Volume: 6

Journal Issue: 1

DOI: 10.1038/s41392-021-00819-6

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.

Authors with CRIS profile

Hans-Martin Jäck Department of Molecular Immunology

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School

Germany (DE) University of Zurich / Universität Zürich (UZH)

Switzerland (CH)

How to cite

APA:

Ruhl, L., Pink, I., Kuehne, J.F., Beushausen, K., Keil, J., Christoph, S.,... Falk, C.S. (2021). Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks. Signal Transduction and Targeted Therapy, 6(1). https://doi.org/10.1038/s41392-021-00819-6

MLA:

Ruhl, Louisa, et al. "Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks." Signal Transduction and Targeted Therapy 6.1 (2021).

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