tetano
Editor, Senior Moderator
J Med Virol
. 2021 Jun 17.
doi: 10.1002/jmv.27144. Online ahead of print.
Soluble angiotensin-converting enzyme 2 is transiently elevated in COVID-19 and correlates with specific inflammatory and endothelial markers
Annika Lundström[SUP] 1 [/SUP], Louise Ziegler[SUP] 2 [/SUP], Sebastian Havervall[SUP] 2 [/SUP], Ann-Sofie Rudberg[SUP] 1 [/SUP], Fien von Meijenfeldt[SUP] 3 [/SUP], Prof Ton Lisman[SUP] 3 [/SUP], Nigel Mackman Prof[SUP] 4 [/SUP], Per Sandén[SUP] 1 [/SUP], Charlotte Thålin[SUP] 2 [/SUP]
Affiliations
Abstract
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 (RAS) and pathology in Coronavirus disease 2019 (COVID-19) remain unclear. We measured soluble ACE2 (sACE2) and sACE levels by ELISA 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 < 0.0001. 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 < 0.0001, but remained higher than in healthy controls, p=0.012. sACE was marginally lower during COVID-19 compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p=0.008. 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. This article is protected by copyright. All rights reserved.
Keywords: Angiotensin-converting enzyme 2; COVID-19; inflammation; renin angiotensin system; risk factor.
. 2021 Jun 17.
doi: 10.1002/jmv.27144. Online ahead of print.
Soluble angiotensin-converting enzyme 2 is transiently elevated in COVID-19 and correlates with specific inflammatory and endothelial markers
Annika Lundström[SUP] 1 [/SUP], Louise Ziegler[SUP] 2 [/SUP], Sebastian Havervall[SUP] 2 [/SUP], Ann-Sofie Rudberg[SUP] 1 [/SUP], Fien von Meijenfeldt[SUP] 3 [/SUP], Prof Ton Lisman[SUP] 3 [/SUP], Nigel Mackman Prof[SUP] 4 [/SUP], Per Sandén[SUP] 1 [/SUP], Charlotte Thålin[SUP] 2 [/SUP]
Affiliations
- PMID: 34138483
- DOI: 10.1002/jmv.27144
Abstract
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 (RAS) and pathology in Coronavirus disease 2019 (COVID-19) remain unclear. We measured soluble ACE2 (sACE2) and sACE levels by ELISA 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 < 0.0001. 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 < 0.0001, but remained higher than in healthy controls, p=0.012. sACE was marginally lower during COVID-19 compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p=0.008. 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. This article is protected by copyright. All rights reserved.
Keywords: Angiotensin-converting enzyme 2; COVID-19; inflammation; renin angiotensin system; risk factor.