Cardiovascular Manifestations and Mechanisms in Patients with COVID-19

Dou, Qingyu; Wei, Xin; Zhou, Kehua; Yang, Shujuan; Jia, Peng

doi:10.1016/j.tem.2020.10.001

Cited by 63 publications

(70 citation statements)

References 126 publications

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“…The primary route of entry for SARS-CoV-2 are the airway epithelial cells, after which it migrates to the lung alveolar epithelial cells, where it rapidly replicates and triggers a massive immune response called the "cytokine storm, " leading to "ARDS" and respiratory failure (4-7). The surface receptor that SARS-CoV-2 uses for cellular entry, the ACE2, is widely present in all cell types, including endothelial cells (EC) of small resistance arteries (20)(21)(22). Available evidence suggests COVID-19 causes severe vascular damage by disrupting endothelial function (1,(9)(10)(11).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Spike Protein Induces Degradation of Junctional Proteins That Maintain Endothelial Barrier Integrity

Raghavan

Kenchappa

Leo

2021

Front. Cardiovasc. Med.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the Angiotensin converting enzyme 2 (ACE2) receptor present on the cell surface to enter cells. Angiotensin converting enzyme 2 is present in many cell types including endothelial cells, where it functions to protect against oxidative damage. There is growing evidence to suggest that coronavirus disease (COVID-19) patients exhibit a wide range of post-recovery symptoms and shows signs related to cardiovascular and specifically, endothelial damage. We hypothesized that these vascular symptoms might be associated with disrupted endothelial barrier integrity. This was investigated in vitro using endothelial cell culture and recombinant SARS-CoV-2 spike protein S1 Receptor-Binding Domain (Spike). Mouse brain microvascular endothelial cells from normal (C57BL/6 mice) and diabetic (db/db) mice were used. An endothelial transwell permeability assay revealed increased permeability in diabetic cells as well as after Spike treatment. The expression of VE-Cadherin, an endothelial adherens junction protein, JAM-A, a tight junctional protein, Connexin-43, a gap junctional protein, and PECAM-1, were all decreased significantly after Spike treatment in control and to a greater extent, in diabetic cells. In control cells, Spike treatment increased association of endothelial junctional proteins with Rab5a, a mediator of the endocytic trafficking compartment. In cerebral arteries isolated from control and diabetic animals, Spike protein had a greater effect in downregulating expression of endothelial junctional proteins in arteries from diabetic animals than from control animals. In conclusion, these experiments reveal that Spike-induced degradation of endothelial junctional proteins affects endothelial barrier function and is the likely cause of vascular damage observed in COVID-19 affected individuals.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Spike Protein Induces Degradation of Junctional Proteins That Maintain Endothelial Barrier Integrity

Raghavan

Kenchappa

Leo

2021

Front. Cardiovasc. Med.

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“…However, the exact pathophysiological mechanisms underlying myocardial injury induced by COVID-19 remain to be fully elucidated. The possible mechanisms include the direct damage to cardiomyocytes of SARS-CoV-2 infection through angiotensin-converting enzyme 2, cytokine storm precipitated by overactivation of the immune response, dysregulation of the renin–angiotensin–aldosterone system, and disturbances of coagulation and microcirculation-induced hypoxia ( 3 , 5 , 25 ). A previous study revealed a critical role of SARS-CoV in transforming growth factor β signaling, which is a predominant regulator of cardiac fibrosis ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Cardiac Involvement in Recovered Patients From COVID-19: A Preliminary 6-Month Follow-Up Study

Deng

et al. 2021

Front. Cardiovasc. Med.

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Background: Accumulating evidence has revealed that coronavirus disease 2019 (COVID-19) patients may be complicated with myocardial injury during hospitalization. However, data regarding persistent cardiac involvement in patients who recovered from COVID-19 are limited. Our goal is to further explore the sustained impact of COVID-19 during follow-up, focusing on the cardiac involvement in the recovered patients.Methods: In this prospective observational follow-up study, we enrolled a total of 40 COVID-19 patients (20 with and 20 without cardiac injury during hospitalization) who were discharged from Zhongnan Hospital of Wuhan University for more than 6 months, and 27 patients (13 with and 14 without cardiac injury during hospitalization) were finally included in the analysis. Clinical information including self-reported symptoms, medications, laboratory findings, Short Form 36-item scores, 6-min walk test, clinical events, electrocardiogram assessment, echocardiography measurement, and cardiac magnetic resonance imaging was collected and analyzed.Results: Among 27 patients finally included, none of patients reported any obvious cardiopulmonary symptoms at the 6-month follow-up. There were no statistically significant differences in terms of the quality of life and exercise capacity between the patients with and without cardiac injury. No significant abnormalities were detected in electrocardiogram manifestations in both groups, except for nonspecific ST-T changes, premature beats, sinus tachycardia/bradycardia, PR interval prolongation, and bundle-branch block. All patients showed normal cardiac structure and function, without any statistical differences between patients with and without cardiac injury by echocardiography. Compared with patients without cardiac injury, patients with cardiac injury exhibited a significantly higher positive proportion in late gadolinium enhancement sequences [7/13 (53.8%) vs. 1/14 (7.1%), p = 0.013], accompanied by the elevation of circulating ST2 level [median (interquartile range) = 16.6 (12.1, 22.5) vs. 12.5 (9.5, 16.7); p = 0.044]. Patients with cardiac injury presented higher levels of aspartate aminotransferase, creatinine, high-sensitivity troponin I, lactate dehydrogenase, and N-terminal pro–B-type natriuretic peptide than those without cardiac injury, although these indexes were within the normal range for all recovered patients at the 6-month follow-up. Among patients with cardiac injury, patients with positive late gadolinium enhancement presented higher cardiac biomarker (high-sensitivity troponin I) and inflammatory factor (high-sensitivity C-reactive protein) on admission than the late gadolinium enhancement–negative subgroup.Conclusions: Our preliminary 6-month follow-up study with a limited number of patients revealed persistent cardiac involvement in 29.6% (8/27) of recovered patients from COVID-19 after discharge. Patients with cardiac injury during hospitalization were more prone to develop cardiac fibrosis during their recovery. Among patients with cardiac injury, those with relatively higher cardiac biomarkers and inflammatory factors on admission appeared more likely to have cardiac involvement in the convalescence phase.

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“…Our study demonstrated 18% incidence of cardiovascular events and carried 45.2% mortality rate in this metropolitan sample population cohort. COVID-19 can cause cardiovascular complications or deterioration of coexisting cardiovascular diseases through direct or indirect mechanisms, including viral toxicity, dysregulation of the renin–angiotensin–aldosterone system, endothelial cell damage and thromboinflammation, cytokine storm, and oxygen supply–demand mismatch 24 , 25 . Published clinical studies suggested COVID-19 itself might induce myocardial injury, arrhythmia, acute coronary syndrome, and venous thromboembolism 5 , 26 , 27 .…”

Section: Discussionmentioning

confidence: 99%

Outcomes and Risk Factors for Cardiovascular Events in Hospitalized COVID-19 Patients

Samanapally

Nathala

et al. 2021

Journal of Cardiothoracic and Vascular Anesthesia

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Objective To analyze outcomes and risk factors of cardiovascular events in a metropolitan COVID-19 database, and to perform a subgroup analysis in African American populations to determine whether outcomes and risk factors are influenced by race. Design Retrospective cohort analysis from March 9, 2020 to June 20, 2020. Setting Population-based study in Louisville, KY, USA Participants 700 adult inpatients hospitalized with COVID-19. Interventions N/A Measurements and Main Results: Our cohort consisted of 126 patients (18%) with cardiovascular events and 574 patients without cardiovascular events. Patients with cardiovascular events had a much higher mortality rate than those without cardiovascular events (45.2% vs. 8.7%, p <0.001). There was no difference between African Americans and Whites regarding mortality (43.9% vs 46.3%, p =1) and length of stay for survivors (11 days vs. 9.5 days, p =0.301). Multiple logistics regression analysis suggested that male, race, lower SaO2/FiO2, higher serum potassium, lower serum albumin, and number of cardiovascular co-morbidities were highly associated with the occurrence of cardiovascular events in COVID-19 patients. Lower serum albumin and neoplastic/immune compromised diseases were highly associated with cardiovascular events for African American COVID-19 patients. SaO2/FiO2 ratio and cardiovascular comorbidity count were significantly associated with cardiovascular events in white patients. Conclusions : Cardiovascular events were prevalent and associated with worse outcomes in hospitalized patients with COVID-19. Outcomes of cardiovascular events in African American and white COVID-19 patients were similar after propensity score matching analysis. There were common and unique risk factors for cardiovascular events in African American COVID-19 patients when compared with white patients.

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Cardiovascular Manifestations and Mechanisms in Patients with COVID-19

Cited by 63 publications

References 126 publications

SARS-CoV-2 Spike Protein Induces Degradation of Junctional Proteins That Maintain Endothelial Barrier Integrity

SARS-CoV-2 Spike Protein Induces Degradation of Junctional Proteins That Maintain Endothelial Barrier Integrity

Cardiac Involvement in Recovered Patients From COVID-19: A Preliminary 6-Month Follow-Up Study

Outcomes and Risk Factors for Cardiovascular Events in Hospitalized COVID-19 Patients

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