A dramatic rise in serum ACE2 activity in a critically ill COVID-19 patient

Abstract

Endothelial cells express surface angiotensin-converting enzyme 2 (ACE2), the main receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that promotes the infection of endothelial cells showing activation and damage. Bronchoalveolar lavage fluid from coronavirus disease-2019 (COVID-19) subjects showed a critical imbalance in the renin-angiotensin-aldosterone system with the upregulated expression of ACE2. Recently, intravenous recombinant ACE2 was reported as an effective therapy in severe COVID-19 by blocking the viral entry to target cells. Here, we present a case of a critically ill COVID-19 patient with acute respiratory distress syndrome where circulating ACE2 was first measured to monitor disease prognosis. ACE2 activity increased about 40-fold over the normal range and showed a distinct time course as compared to 2-3-fold higher levels of endothelium biomarkers. Although the level of soluble E-selectin followed the clinical status of our patient similar to ferritin and IL-6 levels, the dramatic rise in serum ACE2 activity may act as an endogenous nonspecific protective mechanism against SARS-CoV-2 infection that preceded the recovery of our patient.

Increased angiotensin-converting enzyme 2, sRAGE and immune activation, but lowered calcium and magnesium in COVID-19: association with chest CT abnormalities and lowered peripheral oxygen saturation

“…As described in the Introduction, only a few studies reported increased ACE2 levels in patients with SARS-CoV-2 infection and COVID-19 (Nagy et al ., 2021, Patel et al ., 2021). ACE2 concentrations are strongly related to ACE2 catalytic activity (Zhang et al ., 2018).…”

“…Recent studies showed increased levels of angiotensin-converting enzyme 2 (ACE2) following SARS-CoV-2 infection (Patel et al, 2021), and a case report showed very high ACE2 levels in a critically ill COVID-19 patient (Nagy et al, 2021). ACE2 is a common binding site for both SARS-CoV and SARS-CoV-2 (Zhu et al, 2018, Hoffmann et al, 2020.…”

ICODE: the international COVID-19 thrombosis biomarkers colloquium—novel soluble biomarkers: circulating cell-free nucleic acids and other molecules

“…A case report recently described the increase of serum ACE2 in a COVID-19 patient presenting with ARDS [ 16 ].…”

Multifunctional angiotensin converting enzyme 2, the SARS-CoV-2 entry receptor, and critical appraisal of its role in acute lung injury

“…In other recent studies, neither down- nor upregulation of ACE2 was observed in human cell lines infected with SARS-CoV-2 [ 228 , 229 , 280 ]. In COVID-19 patients, plasma levels and enzymatic activity of ACE2 were found increased [ 281 , 282 ] or not altered [ 278 , 283 , 284 ]. On the other hand, plasma levels of DPP4, the entry receptor for MERS-CoV, were reported to be decreased in COVID-19 patients [ 285 ] and in patients infected with MERS-CoV [ 286 ].…”