Soluble angiotensin‐converting enzyme 2 is transiently elevated in COVID‐19 and correlates with specific inflammatory and endothelial markers

• Published in: Journal of Medical Virology Vol. 93; no. 10; pp. 5908 - 5916
• Main Authors: Lundström, Annika, Ziegler, Louise, Havervall, Sebastian, Rudberg, Ann‐Sofie, Meijenfeldt, Fien, Lisman, Ton, Mackman, Nigel, Sandén, Per, Thålin, Charlotte
• Format: Journal Article Web Resource
• Language: English
• Published: United States John Wiley & Sons, Inc 01.10.2021; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Subjects: ACE2; Adult; Aged; Angiotensin; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - blood; Biomarkers - blood; Coagulation factors; Conversion; Coronaviruses; Correlation; COVID-19; COVID-19 - blood; Dimers; Enzymes; Female; Follow-Up Studies; Humans; Inflammation; Interleukin 6; Male; Markers; Medicin och hälsovetenskap; Middle Aged; Patients; Peptidyl-Dipeptidase A - blood; Plasminogen activator inhibitors; Renin; Renin-Angiotensin System; Respiratory diseases; Risk analysis; risk factor; Risk Factors; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Shedding; Tumor necrosis factor-α; Viral diseases; Virology; Von Willebrand factor; COVID-19; angiotensin-converting enzyme 2; renin angiotensin system; inflammation; risk factor
• ISSN: 0146-6615; 1096-9071; 1096-9071
• DOI: 10.1002/jmv.27144

The main entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is angiotensin‐converting enzyme 2 (ACE2). SARS‐CoV‐2 interactions with ACE2 may increase ectodomain shedding but consequences for the renin‐angiotensin system and pathology in Coronavirus disease 2019 (COVID‐19) remain unclear. We measured soluble ACE2 (sACE2) and sACE levels by enzyme‐linked immunosorbent assay in 114 hospital‐treated COVID‐19 patients compared with 10 healthy controls; follow‐up samples after four months were analyzed for 58 patients. Associations between sACE2 respectively sACE and risk factors for severe COVID‐19, outcome, and inflammatory markers were investigated. Levels of sACE2 were higher in COVID‐19 patients than in healthy controls, median 5.0 (interquartile range 2.8–11.8) ng/ml versus 1.4 (1.1–1.6) ng/ml, p < .0001. sACE2 was higher in men than women but was not affected by other risk factors for severe COVID‐19. sACE2 decreased to 2.3 (1.6–3.9) ng/ml at follow‐up, p < .0001, but remained higher than in healthy controls, p = .012. sACE was marginally lower during COVID‐19 compared with at follow‐up, 57 (45–70) ng/ml versus 72 (52–87) ng/ml, p = .008. Levels of sACE2 and sACE did not differ depending on survival or disease severity. sACE2 during COVID‐19 correlated with von Willebrand factor, factor VIII and D‐dimer, while sACE correlated with interleukin 6, tumor necrosis factor α, and plasminogen activator inhibitor 1. Conclusions: sACE2 was transiently elevated in COVID‐19, likely due to increased shedding from infected cells. sACE2 and sACE during COVID‐19 differed in correlations with markers of inflammation and endothelial dysfunction, suggesting release from different cell types and/or vascular beds.