Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)?

doi:10.1183/13993003.01634-2020

Editorial

. 2020 Jul 30;56(1):2001634.

doi: 10.1183/13993003.01634-2020. Print 2020 Jul.

Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)?

Alice Huertas^{1

2

3}, David Montani^{4

2

3}, Laurent Savale^{4

2

3}, Jérémie Pichon^{4

2

3}, Ly Tu^{4

2}, Florence Parent^{4

2

3}, Christophe Guignabert^{4

2}, Marc Humbert^{4

2

3}

Affiliations

¹ Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France alice.huertas@inserm.fr.
² INSERM UMR_S 999 «Pulmonary Hypertension: Pathophysiology and Novel Therapies», Hôpital Marie Lannelongue, Le Plessis-Robinson, France.
³ Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
⁴ Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France.

PMID: 32554538
PMCID: PMC7301835
DOI: 10.1183/13993003.01634-2020

Editorial

Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)?

Alice Huertas et al. Eur Respir J. 2020.

. 2020 Jul 30;56(1):2001634.

doi: 10.1183/13993003.01634-2020. Print 2020 Jul.

Authors

Alice Huertas^{1

2

3}, David Montani^{4

2

3}, Laurent Savale^{4

2

3}, Jérémie Pichon^{4

2

3}, Ly Tu^{4

2}, Florence Parent^{4

2

3}, Christophe Guignabert^{4

2}, Marc Humbert^{4

2

3}

Affiliations

¹ Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France alice.huertas@inserm.fr.
² INSERM UMR_S 999 «Pulmonary Hypertension: Pathophysiology and Novel Therapies», Hôpital Marie Lannelongue, Le Plessis-Robinson, France.
³ Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
⁴ Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France.

PMID: 32554538
PMCID: PMC7301835
DOI: 10.1183/13993003.01634-2020

Abstract

Endothelial cell dysfunction and impaired microcirculatory function contribute markedly to life-threatening complications of COVID-19, such as venous thromboembolic disease and multiple organ involvement https://bit.ly/3cZMjKV

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Conflict of interest statement

Conflict of interest: A. Huertas has nothing to disclose. Conflict of interest: D. Montani reports grants and personal fees from Actelion and Bayer, personal fees from GSK, Pfizer, Chiesi and Boehringer, grants, personal fees and non-financial support from MSD, non-financial support from Acceleron, outside the submitted work. Conflict of interest: L. Savale reports personal fees and non-financial support from Actelion and Bayer, grants and personal fees from GSK, outside the submitted work. Conflict of interest: J. Pichon has nothing to disclose. Conflict of interest: L. Tu has nothing to disclose. Conflict of interest: F. Parent reports grants from Bayer, CSL Behring and Sanofi, outside the submitted work. Conflict of interest: C. Guignabert has nothing to disclose. Conflict of interest: M. Humbert reports grants and personal fees from Actelion, Bayer, GSK and Acceleron, personal fees from Merck and United Therapeutics, outside the submitted work.

Figures

**FIGURE 1**
Schematic representation of hypothetical mechanisms by which the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes endothelial dysfunction and pulmonary vascular changes. Following cleavage of its S protein, SARS-CoV-2 was reported to enter human cells *via* binding to angiotensin-converting enzyme 2 (ACE-2). This transmembrane ACE-2 receptor is widely expressed in various pulmonary cells including type II alveolar cells, macrophages, endothelial, smooth muscle cells and perivascular pericytes. This causes uncontrolled inflammation (1), accompanied by micro-thrombosis and occlusion of small pulmonary vessels (2), and impaired endothelial regulation of vascular tone (3), leading to alveolo-capillary barrier disruption (4). Ang: angiotensin; AT: angiotensin receptor; IL: interleukin; MAS: macrophage activation syndrome; MIF: macrophage migration inhibitory factor; NO: nitric oxide; PAF: platelet activating factor; PAI-1: plasminogen activator inhibitor-1; PGI2: prostaglandin I2; TF: tissue factor; TNF: tumour necrosis factor; tPA: tissue plasminogen activator.

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Comment in

Endothelial to mesenchymal transition: a precursor to post-COVID-19 interstitial pulmonary fibrosis and vascular obliteration?
Eapen MS, Lu W, Gaikwad AV, Bhattarai P, Chia C, Hardikar A, Haug G, Sohal SS. Eapen MS, et al. Eur Respir J. 2020 Oct 15;56(4):2003167. doi: 10.1183/13993003.03167-2020. Print 2020 Oct. Eur Respir J. 2020. PMID: 32859681 Free PMC article.

Comment on

Venous thromboembolism in SARS-CoV-2 patients: only a problem in ventilated ICU patients, or is there more to it?
Criel M, Falter M, Jaeken J, Van Kerrebroeck M, Lefere I, Meylaerts L, Mesotten D, Vander Laenen M, Fivez T, Thomeer M, Ruttens D. Criel M, et al. Eur Respir J. 2020 Jul 30;56(1):2001201. doi: 10.1183/13993003.01201-2020. Print 2020 Jul. Eur Respir J. 2020. PMID: 32398294 Free PMC article.
Pulmonary embolism in patients with COVID-19 pneumonia.
Bompard F, Monnier H, Saab I, Tordjman M, Abdoul H, Fournier L, Sanchez O, Lorut C, Chassagnon G, Revel MP. Bompard F, et al. Eur Respir J. 2020 Jul 30;56(1):2001365. doi: 10.1183/13993003.01365-2020. Print 2020 Jul. Eur Respir J. 2020. PMID: 32398297 Free PMC article.

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Cardiovascular Health and Disease in the Context of COVID-19.
Umbrajkar S, Stankowski RV, Rezkalla S, Kloner RA. Umbrajkar S, et al. Cardiol Res. 2021 Apr;12(2):67-79. doi: 10.14740/cr1199. Epub 2021 Feb 23. Cardiol Res. 2021. PMID: 33738009 Free PMC article. Review.
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References

1. Delmas B, Gelfi J, L'Haridon R, et al. . Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV. Nature 1992; 357: 417–420. doi:10.1038/357417a0 - DOI - PMC - PubMed
1. Yeager CL, Ashmun RA, Williams RK, et al. . Human aminopeptidase N is a receptor for human coronavirus 229E. Nature 1992; 357: 420–422. doi:10.1038/357420a0 - DOI - PMC - PubMed
1. Dveksler GS, Dieffenbach CW, Cardellichio CB, et al. . Several members of the mouse carcinoembryonic antigen-related glycoprotein family are functional receptors for the coronavirus mouse hepatitis virus-A59. J Virol 1993; 67: 1–8. doi:10.1128/JVI.67.1.1-8.1993 - DOI - PMC - PubMed
1. Li W, Moore MJ, Vasilieva N, et al. . Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426: 450–454. doi:10.1038/nature02145 - DOI - PMC - PubMed
1. Holmes KV. SARS-associated coronavirus. N Engl J Med 2003; 348: 1948–1951. doi:10.1056/NEJMp030078 - DOI - PubMed

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[1] Delmas B, Gelfi J, L'Haridon R, et al. . Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV. Nature 1992; 357: 417–420. doi:10.1038/357417a0 - DOI - PMC - PubMed

[2] Delmas B, Gelfi J, L'Haridon R, et al. . Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV. Nature 1992; 357: 417–420. doi:10.1038/357417a0 - DOI - PMC - PubMed

[3] Yeager CL, Ashmun RA, Williams RK, et al. . Human aminopeptidase N is a receptor for human coronavirus 229E. Nature 1992; 357: 420–422. doi:10.1038/357420a0 - DOI - PMC - PubMed

[4] Yeager CL, Ashmun RA, Williams RK, et al. . Human aminopeptidase N is a receptor for human coronavirus 229E. Nature 1992; 357: 420–422. doi:10.1038/357420a0 - DOI - PMC - PubMed

[5] Dveksler GS, Dieffenbach CW, Cardellichio CB, et al. . Several members of the mouse carcinoembryonic antigen-related glycoprotein family are functional receptors for the coronavirus mouse hepatitis virus-A59. J Virol 1993; 67: 1–8. doi:10.1128/JVI.67.1.1-8.1993 - DOI - PMC - PubMed

[6] Dveksler GS, Dieffenbach CW, Cardellichio CB, et al. . Several members of the mouse carcinoembryonic antigen-related glycoprotein family are functional receptors for the coronavirus mouse hepatitis virus-A59. J Virol 1993; 67: 1–8. doi:10.1128/JVI.67.1.1-8.1993 - DOI - PMC - PubMed

[7] Li W, Moore MJ, Vasilieva N, et al. . Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426: 450–454. doi:10.1038/nature02145 - DOI - PMC - PubMed

[8] Li W, Moore MJ, Vasilieva N, et al. . Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426: 450–454. doi:10.1038/nature02145 - DOI - PMC - PubMed

[9] Holmes KV. SARS-associated coronavirus. N Engl J Med 2003; 348: 1948–1951. doi:10.1056/NEJMp030078 - DOI - PubMed

[10] Holmes KV. SARS-associated coronavirus. N Engl J Med 2003; 348: 1948–1951. doi:10.1056/NEJMp030078 - DOI - PubMed

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Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)?

Affiliations

Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)?

Authors

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Abstract

Conflict of interest statement

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