Table 6.

Clinical relevance of cardiovascular and circulatory cells in patients with COVID-19 and potential underlying mechanisms leading to cardiovascular disease.

Contributing cells	Clinical relevance	Potential underlying mechanisms leading to CVD
Cardiovascular cells		Cardiovascular cell-related mechanisms:
Cardiomyocytes1	Wide expression of ACE2	SARS-CoV-2 uses ACE2 as a cell receptor → direct myocardial damage
Cardiac pericytes2	High ACE2 expression	SARS-CoV-2 uses ACE2 as a cell receptor → pericyte is a potential host cell targeted by SARS-CoV-2 in cardiac tissue capillary → capillary endothelial cells dysfunction → coronary microvascular dysfunction
Endothelial cells3, 4, 5	Evidence of direct SARS-CoV-2 infection of the endothelial cells and diffuse endothelial inflammation	Increased ACE2 expression by endothelial cells and evidence of direct viral infection of vascular organoids in vitro → endothelial inflammation (“endotheliitis”) and increased leukocyte infiltration in heart tissue → atherosclerotic plaque destabilization → acute coronary syndrome
Blood cells		Leukocyte-related mechanisms:
Lymphocytes6, 7, 8, 9, 10	↓ in all cases, especially in severe disease	•↓ in the number of lymphocytes and NK cells due to functional exhaustion and apoptosis → decreased viral clearance → direct viral infection of cardiomyocytes, cardiac pericytes, and endothelial cells
CD4+ T cells11, 12, 13, 14	↓ in severe disease ✓Autopsy-confirmed CD4+ T infiltration of myocardium	•Apoptosis of plaque infiltrating lymphocytes → plaque destabilization
CD8+ T cells15,16	↓ in severe disease	•CD4+ T cells infiltration of myocardium → inflammatory cardiomyopathy
NK cells14,15	↓ in all cases	•↑ in the number of neutrophils → neutrophil plugging → epicardial and/or microvascular obstruction
Neutrophils17, 18, 19	↑ in severe disease	Platelet-related mechanism: Platelets become activated → platelets adhere to vascular endothelium promoting further recruitment of leukocytes to vascular wall → vascular inflammation and tissue inflammation → inflammatory cardiomyopathy, atherothrombosis, and vasculitis
Platelets177,178	↓ in severe disease

ACE2: angiotensin-converting enzyme 2, COVID-19: coronavirus disease 2019, CV: cardiovascular.

CVD: cardiovascular disease, NK: natural killer, and SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.