SARS-CoV-2 receptor is co-expressed with elements of the kinin-kallikrein, renin-angiotensin and coagulation systems in alveolar cells

Author(s)

Sidarta-Oliveira, Davi ^{[1, 2]} ; Jara, Carlos Poblete ^{[1, 3]} ; Ferruzzi, Adriano J. ^{[4, 5]} ; Skaf, Munir S. ^{[4, 5]} ; Velander, William H. ^[6] ; Araujo, Eliana P. ^{[1, 3]} ; Velloso, Licio A. ^[1]

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Obes & Comorbid Res Ctr, Lab Cell Signaling, Bloco Z, Campus Univ Zeferino Vaz, BR-13083864 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Sch Med Sci, Phys Scientist Grad Program, Campinas - Brazil

^[3] Univ Estadual Campinas, Nursing Sch, Campinas - Brazil

^[4] Univ Estadual Campinas, Inst Chem, Campinas - Brazil

^[5] Univ Estadual Campinas, Ctr Comp Engn & Sci, Campinas - Brazil

^[6] Univ Nebraska, Dept Chem & Biomol Engn, Lincoln, NE 68583 - USA

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 NOV 11 2020.
• Web of Science Citations: 12

Abstract

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 similar to 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. (AU)

• FAPESP's process: 13/08293-7 - CCES - Center for Computational Engineering and Sciences
• Grantee: Munir Salomao Skaf
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
• Grantee: Licio Augusto Velloso
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC