Is Endothelial Dysfunction the Concealed Cornerstone of COVID-19?
Dear Editor,
In their paper (1), Chen et al. reported hypertension, cardiovascular disease, and diabetes as frequent comorbidities in patients with COVID-19, consistent with other studies (2-4). Endothelial dysfunction is a common feature of all these disorders. Furthermore, all of the co-factors harnessed by SARS-CoV-2 coronavirus to access host cells, including ACE2, CD147, sialic acid receptor, and TMPRSS2, are expressed by human endothelial cells (5, 6).
Hence, our theory is that SARS-CoV-2 could directly affect endothelial cells, explaining the main systemic manifestations observed in COVID-19 patients, including thrombotic complications (4, 7). Of interest, Chen et al. are in line with our view, reporting higher D-dimer levels in deceased patients compared to survived patients (1). If our hypothesis is correct, several drugs that have been shown to improve endothelial function, such as modulators of the renin-angiotensin-aldosterone system, anti-coagulants, statins, and anti-inflammatory drugs, could be extremely helpful in the treatment of COVID-19 patients. Do the authors have any data regarding the percentage of patients in their study who were receiving these drugs and whether such treatment had any effect on the outcome or on the severity of the disease?
References
(1) Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 26;368:m1091. doi: 10.1136/bmj.m1091.
(2) Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020 Apr 6. doi: 10.1001/jama.2020.5394.
(3) McMichael TM, Currie DW, Clark S, et al. Epidemiology of Covid-19 in a long-term care facility in King County, Washington. N Engl J Med. 2020; in press.
(4) Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020; in press.
(5) Ou X, Liu Y, Lei X, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020 Mar 27;11(1):1620. doi: 10.1038/s41467-020-15562-9.
(6) Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020; in press.
(7) Tang N, Li D, Wang X and Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844-847.
Gaetano Santulli, MD, PhD
Albert Einstein College of Medicine, Montefiore University Hospital, New York, NY, USA
Federico II University, Naples, Italy; gaetano.santulli@einstein.yu.edu
Jessica Gambardella, PhD
Albert Einstein College of Medicine, New York, NY, USA
Federico II University, Naples, Italy; jessica.gambardella@einstein.yu.edu
Competing interests:
No competing interests
19 April 2020
Gaetano Santulli
Cardiologist
Marco Bruno Morelli, Jessica Gambardella
Einstein College of Medicine - Montefiore University Hospital
Einstein College of Medicine - Montefiore University Hospital
Rapid Response:
Is Endothelial Dysfunction the Concealed Cornerstone of COVID-19?
Dear Editor,
In their paper (1), Chen et al. reported hypertension, cardiovascular disease, and diabetes as frequent comorbidities in patients with COVID-19, consistent with other studies (2-4). Endothelial dysfunction is a common feature of all these disorders. Furthermore, all of the co-factors harnessed by SARS-CoV-2 coronavirus to access host cells, including ACE2, CD147, sialic acid receptor, and TMPRSS2, are expressed by human endothelial cells (5, 6).
Hence, our theory is that SARS-CoV-2 could directly affect endothelial cells, explaining the main systemic manifestations observed in COVID-19 patients, including thrombotic complications (4, 7). Of interest, Chen et al. are in line with our view, reporting higher D-dimer levels in deceased patients compared to survived patients (1). If our hypothesis is correct, several drugs that have been shown to improve endothelial function, such as modulators of the renin-angiotensin-aldosterone system, anti-coagulants, statins, and anti-inflammatory drugs, could be extremely helpful in the treatment of COVID-19 patients. Do the authors have any data regarding the percentage of patients in their study who were receiving these drugs and whether such treatment had any effect on the outcome or on the severity of the disease?
References
(1) Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020 Mar 26;368:m1091. doi: 10.1136/bmj.m1091.
(2) Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020 Apr 6. doi: 10.1001/jama.2020.5394.
(3) McMichael TM, Currie DW, Clark S, et al. Epidemiology of Covid-19 in a long-term care facility in King County, Washington. N Engl J Med. 2020; in press.
(4) Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020; in press.
(5) Ou X, Liu Y, Lei X, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020 Mar 27;11(1):1620. doi: 10.1038/s41467-020-15562-9.
(6) Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020; in press.
(7) Tang N, Li D, Wang X and Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844-847.
Gaetano Santulli, MD, PhD
Albert Einstein College of Medicine, Montefiore University Hospital, New York, NY, USA
Federico II University, Naples, Italy;
gaetano.santulli@einstein.yu.edu
Marco Bruno Morelli, PhD
Albert Einstein College of Medicine, New York, NY, USA
marco.morelli@einsteinmed.org
Jessica Gambardella, PhD
Albert Einstein College of Medicine, New York, NY, USA
Federico II University, Naples, Italy;
jessica.gambardella@einstein.yu.edu
Competing interests: No competing interests