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Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks.
Ruhl, Louisa; Pink, Isabell; Kühne, Jenny F; Beushausen, Kerstin; Keil, Jana; Christoph, Stella; Sauer, Andrea; Boblitz, Lennart; Schmidt, Julius; David, Sascha; Jäck, Hans-Martin; Roth, Edith; Cornberg, Markus; Schulz, Thomas F; Welte, Tobias; Höper, Marius M; Falk, Christine S.
  • Ruhl L; Institute of Transplant Immunology, MHH, D, Hanover, Germany.
  • Pink I; Department of Pneumology, MHH, D, Hanover, Germany.
  • Kühne JF; Institute of Transplant Immunology, MHH, D, Hanover, Germany.
  • Beushausen K; Institute of Transplant Immunology, MHH, D, Hanover, Germany.
  • Keil J; Institute of Transplant Immunology, MHH, D, Hanover, Germany.
  • Christoph S; Institute of Transplant Immunology, MHH, D, Hanover, Germany.
  • Sauer A; Department of Pneumology, MHH, D, Hanover, Germany.
  • Boblitz L; Department of Pneumology, MHH, D, Hanover, Germany.
  • Schmidt J; Department of Pneumology, MHH, D, Hanover, Germany.
  • David S; Department of Intensive Care Medicine, University of Zurich, CH, Zurich, Switzerland.
  • Jäck HM; Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, Friedrich-Alexander University Erlangen-Nürnberg, D, Erlangen, Germany.
  • Roth E; Division of Molecular Immunology, Internal Medicine III, Nikolaus-Fiebiger-Center of Molecular Medicine, Friedrich-Alexander University Erlangen-Nürnberg, D, Erlangen, Germany.
  • Cornberg M; Department of Gastroenterology Hepatology and Endocrinology, MHH, D, Hanover, Germany.
  • Schulz TF; Center for Individualized Infection Medicine CiiM, Hanover, Germany.
  • Welte T; Institute of Virology, MHH, D, Hanover, Germany.
  • Höper MM; German Center for Infection Research, DZIF, TTU-IICH, Marburg, Germany.
  • Falk CS; Excellence Cluster 2155 RESIST, MHH, Hanover, Germany.
Signal Transduct Target Ther ; 6(1): 418, 2021 12 10.
Article in English | MEDLINE | ID: covidwho-1565706
Preprint
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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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Endothelium, Vascular / Blood Proteins / Cytokine Release Syndrome / SARS-CoV-2 / COVID-19 / Lymphopenia / Antibodies, Viral Type of study: Diagnostic study / Observational study / Prognostic study Topics: Variants Language: English Journal: Signal Transduct Target Ther Year: 2021 Document Type: Article Affiliation country: S41392-021-00819-6

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Endothelium, Vascular / Blood Proteins / Cytokine Release Syndrome / SARS-CoV-2 / COVID-19 / Lymphopenia / Antibodies, Viral Type of study: Diagnostic study / Observational study / Prognostic study Topics: Variants Language: English Journal: Signal Transduct Target Ther Year: 2021 Document Type: Article Affiliation country: S41392-021-00819-6