COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options

Tomasz J Guzik; Saidi A Mohiddin; Anthony Dimarco; Vimal Patel; Kostas Savvatis; Federica M Marelli-Berg; Meena S Madhur; Maciej Tomaszewski; Pasquale Maffia; Fulvio D'Acquisto; Stuart A Nicklin; Ali J Marian; Ryszard Nosalski; Eleanor C Murray; Bartlomiej Guzik; Colin Berry; Rhian M Touyz; Reinhold Kreutz; Dao Wen Wang; David Bhella; Orlando Sagliocco; Filippo Crea; Emma C Thomson; Iain B McInnes

doi:10.1093/cvr/cvaa106

COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options

Tomasz J Guzik, Saidi A Mohiddin, Anthony Dimarco, Vimal Patel, Kostas Savvatis, Federica M Marelli-Berg, Meena S Madhur, Maciej Tomaszewski, Pasquale Maffia, Fulvio D'Acquisto, Stuart A Nicklin, Ali J Marian, Ryszard Nosalski, Eleanor C Murray, Bartlomiej Guzik, Colin Berry, Rhian M Touyz, Reinhold Kreutz, Dao Wen Wang, David BhellaOrlando Sagliocco, Filippo Crea, Emma C Thomson, Iain B McInnes

Research output: Contribution to journal › Article › peer-review

Abstract

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

Original language	English
Journal	Cardiovascular research
Early online date	30 Apr 2020
DOIs	https://doi.org/10.1093/cvr/cvaa106
Publication status	E-pub ahead of print - 30 Apr 2020

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10.1093/cvr/cvaa106

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Guzik, T. J., Mohiddin, S. A., Dimarco, A., Patel, V., Savvatis, K., Marelli-Berg, F. M., Madhur, M. S., Tomaszewski, M., Maffia, P., D'Acquisto, F., Nicklin, S. A., Marian, A. J., Nosalski, R., Murray, E. C., Guzik, B., Berry, C., Touyz, R. M., Kreutz, R., Wang, D. W., ... McInnes, I. B. (2020). COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovascular research. Advance online publication. https://doi.org/10.1093/cvr/cvaa106

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title = "COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options",

abstract = "The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.",

author = "Guzik, {Tomasz J} and Mohiddin, {Saidi A} and Anthony Dimarco and Vimal Patel and Kostas Savvatis and Marelli-Berg, {Federica M} and Madhur, {Meena S} and Maciej Tomaszewski and Pasquale Maffia and Fulvio D'Acquisto and Nicklin, {Stuart A} and Marian, {Ali J} and Ryszard Nosalski and Murray, {Eleanor C} and Bartlomiej Guzik and Colin Berry and Touyz, {Rhian M} and Reinhold Kreutz and Wang, {Dao Wen} and David Bhella and Orlando Sagliocco and Filippo Crea and Thomson, {Emma C} and McInnes, {Iain B}",

year = "2020",

month = apr,

day = "30",

doi = "10.1093/cvr/cvaa106",

language = "English",

journal = "Cardiovascular research",

issn = "0008-6363",

publisher = "Oxford University Press",

}

Guzik, TJ, Mohiddin, SA, Dimarco, A, Patel, V, Savvatis, K, Marelli-Berg, FM, Madhur, MS, Tomaszewski, M, Maffia, P, D'Acquisto, F, Nicklin, SA, Marian, AJ, Nosalski, R, Murray, EC, Guzik, B, Berry, C, Touyz, RM, Kreutz, R, Wang, DW, Bhella, D, Sagliocco, O, Crea, F, Thomson, EC & McInnes, IB 2020, 'COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options', Cardiovascular research. https://doi.org/10.1093/cvr/cvaa106

TY - JOUR

T1 - COVID-19 and the cardiovascular system

T2 - implications for risk assessment, diagnosis, and treatment options

AU - Guzik, Tomasz J

AU - Mohiddin, Saidi A

AU - Dimarco, Anthony

AU - Patel, Vimal

AU - Savvatis, Kostas

AU - Marelli-Berg, Federica M

AU - Madhur, Meena S

AU - Tomaszewski, Maciej

AU - Maffia, Pasquale

AU - D'Acquisto, Fulvio

AU - Nicklin, Stuart A

AU - Marian, Ali J

AU - Nosalski, Ryszard

AU - Murray, Eleanor C

AU - Guzik, Bartlomiej

AU - Berry, Colin

AU - Touyz, Rhian M

AU - Kreutz, Reinhold

AU - Wang, Dao Wen

AU - Bhella, David

AU - Sagliocco, Orlando

AU - Crea, Filippo

AU - Thomson, Emma C

AU - McInnes, Iain B

PY - 2020/4/30

Y1 - 2020/4/30

N2 - The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

AB - The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

U2 - 10.1093/cvr/cvaa106

DO - 10.1093/cvr/cvaa106

M3 - Article

C2 - 32352535

SN - 0008-6363

JO - Cardiovascular research

JF - Cardiovascular research

ER -