header

Erythrocytes Induce Vascular Dysfunction in COVID-19

55 Pages Posted: 19 Oct 2021 Publication Status: Preprint

See all articles by Ali Mahdi

Ali Mahdi

Karolinska Institutet - Division of Cardiology

Aida Collado

Karolinska Institutet - Division of Cardiology

John Tengbom

Karolinska Institutet

Tong Jiao

Karolinska Institutet

Tigist Wodaje

Karolinska Institutet

Niclas Johanssson

Karolinska Institutet

Filip Farnebo

Karolinska Institutet

Anna Färnert

Karolinska Institutet

Jiangning Yang

Karolinska Institutet

Jon O. Lundberg

Karolinska Institutet - Department of Physiology and Pharmacology

Zhichao Zhou

Karolinska Institutet

John Pernow

Karolinska Institutet - Division of Cardiology

Multiple version iconThere are 2 versions of this paper

Abstract

Background: Vascular injury has been implicated as a major cause of clinical complications in patients with coronavirus disease 2019 (COVID-19) based on autopsy studies showing destruction of the endothelial architecture. Red blood cells (RBCs) are affected by COVID-19 with alterations in their structure and function, possibly altering disease progress. Objectives: This study was designed to test the hypothesis of persistent endothelial dysfunction and that RBCs act as mediators of endothelial dysfunction in COVID-19. Methods and results: COVID-19 patients displayed profound endothelial dysfunction in vivo assessed with pulse amplitude tonometry, both in the acute phase and at follow-up four months later. RBCs but not plasma from COVID-19 patients in the acute phase incubated with healthy rat aorta induced severe endothelial dysfunction ex vivo compared to RBCs from healthy subjects. Further, these RBCs induced vascular arginase 1 and oxidative stress. Consequently, inhibition of vascular arginase or superoxide attenuated endothelial dysfunction induced by RBCs from COVID-19 patients. These RBCs were characterized by increased production of reactive oxygen species and reduced export of the nitric oxide metabolite nitrate. RBCs from COVID-19 patients at follow-up did not affect vascular function. Pre-incubation of RBCs from healthy subjects with interferon-γ impaired endothelial function.Conclusions: This study demonstrates the presence of persistent endothelial dysfunction in an otherwise mainly healthy population hospitalized for COVID-19, and implicates a role of RBCs as mediators of endothelial injury. These data shed light on a new pathological mechanism underlying vascular dysfunction in COVID-19 and lay the foundation for future therapeutic developments.

Keywords: COVID-19, red blood cells, endothelial dysfunction, reactive oxygen species, arginase

Suggested Citation

Mahdi, Ali and Collado, Aida and Tengbom, John and Jiao, Tong and Wodaje, Tigist and Johanssson, Niclas and Farnebo, Filip and Färnert, Anna and Yang, Jiangning and Lundberg, Jon O. and Zhou, Zhichao and Pernow, John, Erythrocytes Induce Vascular Dysfunction in COVID-19. Available at SSRN: https://ssrn.com/abstract=3945298 or http://dx.doi.org/10.2139/ssrn.3945298

Ali Mahdi (Contact Author)

Karolinska Institutet - Division of Cardiology ( email )

Stockholm
Sweden

Aida Collado

Karolinska Institutet - Division of Cardiology ( email )

Stockholm
Sweden

John Tengbom

Karolinska Institutet

Granits väg 4
Section for Integrative Physiology
Solna, 17171
Sweden

Tong Jiao

Karolinska Institutet ( email )

Granits väg 4
Section for Integrative Physiology
Solna, 17171
Sweden

Tigist Wodaje

Karolinska Institutet

Granits väg 4
Section for Integrative Physiology
Solna, 17171
Sweden

Niclas Johanssson

Karolinska Institutet

Granits väg 4
Section for Integrative Physiology
Solna, 17171
Sweden

Filip Farnebo

Karolinska Institutet

Granits väg 4
Section for Integrative Physiology
Solna, 17171
Sweden

Anna Färnert

Karolinska Institutet ( email )

Granits väg 4
Section for Integrative Physiology
Solna, 17171
Sweden

Jiangning Yang

Karolinska Institutet

Granits väg 4
Section for Integrative Physiology
Solna, 17171
Sweden

Jon O. Lundberg

Karolinska Institutet - Department of Physiology and Pharmacology ( email )

Solnavägen 9
Stockholm, SE-171 77
Sweden

Zhichao Zhou

Karolinska Institutet ( email )

Granits väg 4
Section for Integrative Physiology
Solna, 17171
Sweden

John Pernow

Karolinska Institutet - Division of Cardiology ( email )

Stockholm
Sweden

Do you have a job opening that you would like to promote on SSRN?

Paper statistics

Downloads
42
Abstract Views
345
PlumX Metrics