SARS-CoV-2, the pathogenic agent of COVID-19, employs angiotensin converting enzyme-2 (ACE2) as its cell entry receptor. Clinical data reveal that in severe COVID-19, SARS-CoV-2 infects the lung, leading to a frequently lethal triad of respiratory insufficiency, acute cardiovascular failure, and coagulopathy. Physiologically, ACE2 plays a role in the regulation of three systems that could potentially be involved in the pathogenesis of severe COVID-19: the kinin–kallikrein system, resulting in acute lung inflammatory edema; the renin–angiotensin system, promoting cardiovascular instability; and the coagulation system, leading to thromboembolism. Here we assembled a healthy human lung cell atlas meta-analysis with ~ 130,000 public single-cell transcriptomes and show that key elements of the bradykinin, angiotensin and coagulation systems are co-expressed with ACE2 in alveolar cells and associated with their differentiation dynamics, which could explain how changes in ACE2 promoted by SARS-CoV-2 cell entry result in the development of the three most severe clinical components of COVID-19.
【저자키워드】 immunology, Computational biology and bioinformatics, 【초록키워드】 COVID-19, Meta-analysis, SARS-CoV-2, ACE2, Pathogenesis, severe COVID-19, lung, Angiotensin converting enzyme-2, Coagulopathy, clinical, human lung, Thromboembolism, Coagulation system, Inflammatory, Regulation, pathogenic, component, element, infect, Cell, cell entry receptor, resulting, involved, healthy, changes in, alveolar cell, explain, promoted, co-expressed, SARS-CoV-2 cell, single-cell transcriptome, 【제목키워드】 SARS-CoV-2 receptor, Coagulation system, element, alveolar cell, co-expressed,