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Review
. 2020 May 11;9(5):1417.
doi: 10.3390/jcm9051417.

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

Celestino Sardu  1   2 , Jessica Gambardella  3   4 , Marco Bruno Morelli  4   5 , Xujun Wang  4 , Raffaele Marfella  1 , Gaetano Santulli  3   4   5
Affiliations
Review

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

Celestino Sardu et al. J Clin Med. .

Abstract

The symptoms most commonly reported by patients affected by coronavirus disease (COVID-19) include cough, fever, and shortness of breath. However, other major events usually observed in COVID-19 patients (e.g., high blood pressure, arterial and venous thromboembolism, kidney disease, neurologic disorders, and diabetes mellitus) indicate that the virus is targeting the endothelium, one of the largest organs in the human body. Herein, we report a systematic and comprehensive evaluation of both clinical and preclinical evidence supporting the hypothesis that the endothelium is a key target organ in COVID-19, providing a mechanistic rationale behind its systemic manifestations.

Keywords: ACE2, acute kidney injury; COVID; Kawasaki disease; blood pressure; catepsin; coronavirus; cytokine storm; endothelium; heparin.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the paper.

Figures

Figure 1
Figure 1
Endothelial dysfunction is a major determinant of COVID-19. The SARS-CoV-2 coronavirus accesses host cells via the binding of its spike glycoprotein to angiotensin-converting enzyme 2 (ACE2), sialic acid receptor, transmembrane serine protease 2 (TMPRSS2), and extracellular matrix metalloproteinase inducer (CD147); catepsin B and L also participate in virus entry. All of these factors are expressed in endothelial cells. Endothelial dysfunction is a common feature of the clinical manifestations observed in COVID-19 patients. All of the drugs proposed as a potential therapeutic strategy to treat COVID-19 patients have been shown to improve endothelial function, including tocilizumab, colchicine, chloroquine/hydroxychloroquine, azithromycin, and famotidine (see text for details and references).
Figure 2
Figure 2
Angiotensin-converting enzyme inhibitors (ACEi) and blockers of the angiotensin receptor 1 (ARB). Angiotensin II and Angiotensin 1–7 binds heptahelical receptors; namely, angiotensin II can activate AT1R (type 1 angiotensin II receptor) and AT2R (type 2 angiotensin II receptor), whereas angiotensin 1–7 binds the Mas Receptor (MasR). The actions mediated by these receptors are depicted in the figure.
Figure 3
Figure 3
Clinical course of COVID-19 patients. Two main overlapping phases constitute the key pathogenic events in COVID-19: the acute phase represented by viral infection, followed by the immune/inflammatory response. Common clinical and laboratory findings are reported within the arrows at the bottom of the figure.
See this image and copyright information in PMC

References

    1. Fauci A.S., Lane H.C., Redfield R.R. Covid-19—Navigating the Uncharted. N. Engl. J. Med. 2020;382:1268–1269. doi: 10.1056/NEJMe2002387. - DOI - PMC - PubMed
    1. Paules C.I., Marston H.D., Fauci A.S. Coronavirus Infections-More Than Just the Common Cold. JAMA. 2020;323:707. doi: 10.1001/jama.2020.0757. - DOI - PubMed
    1. Hui D.S., Azhar E.E., Madani T.A., Ntoumi F., Kock R., Dar O., Ippolito G., McHugh T.D., Memish Z.A., Drosten C., et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health—The latest 2019 novel coronavirus outbreak in Wuhan, China. Int. J. Infect. Dis. 2020;91:264–266. doi: 10.1016/j.ijid.2020.01.009. - DOI - PMC - PubMed
    1. Zhang H., Penninger J.M., Li Y., Zhong N., Slutsky A.S. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: Molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46:586–590. doi: 10.1007/s00134-020-05985-9. - DOI - PMC - PubMed
    1. Zhou P., Yang X.L., Wang X.G., Hu B., Zhang L., Zhang W., Si H.R., Zhu Y., Li B., Huang C.L., et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–273. doi: 10.1038/s41586-020-2012-7. - DOI - PMC - PubMed

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