Concentrations of Soluble Angiotensin Converting Enzyme 2 (sACE2) in Children and Adults with and without COVID-19

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19) pandemic, leads to illness and death. Various risk factors for a severe course, such as higher age, male gender and pre-existing illnesses are known. However, pathophysiological risk factors are largely unclear. Notably, the mild course of disease in children is conspicuous. Angiotensin converting enzyme 2 (ACE2) serves as a receptor for SARS-CoV-2 and is a key enzyme in infection. Differences in the distribution of ACE2 can provide insights into different courses of COVID-19. Our aim was to elucidate the role of ACE2 as a pathophysiological risk factor by measuring soluble ACE2 (sACE2) via ELISA in blood samples (lithium-heparin-plasma or serum) of 367 individuals including children and adults with and without COVID-19. sACE2-levels were compared between the groups according to age and sex. In adults and children with COVID-19, sACE2-concentrations are significantly higher compared to healthy individuals. sACE2-levels increase with age and are lower in children compared to adults with COVID-19. Sex doesn’t significantly influence sACE2-concentration. It remains unclear whether sACE2 concentrations increase because of the infection and what factors could influence this response. In conclusion, the increase of sACE2-concentration with age could indicate that ACE2 concentrations mirror increased COVID-19 severity.

The Relationship between Soluble Angiotensin-Converting Enzyme Level and Coronavirus Disease 2019 in Children: A Prospective Cohort Study

“…Therefore, studies mostly investigate the blood levels of these enzymes and their relationships with the occurrence and prognosis of COVID-19. 10,14,15 These studies are mostly related to the adult population and examine ACE2.…”

“…20 Some studies have shown positive prognostic results with the use of human recombinant sACE2 in COVID-19. 10,21 However, previous studies suggest that high blood ACE2 concentration is associated with COVID-19 severity 10,22 and also some comorbidities 22,23 that influence the prognosis of COVID-19. 5, 24 Ciaglia et al 7 speculated that the reason for these paradoxes may lie in posttranslational events that regulate protein levels and their balance between membrane-bound and soluble forms of ACE2.…”

“…Furthermore, research on ACE2 has yielded contradictory results. 3,[9][10][11] In this study, we hypothesized that ACE may be associated with the pathogenesis of COVID-19 and soluble ACE (sACE) levels may be used as a prognostic factor for management. Therefore, our aims were (1) to assess whether sACE levels were associated with pediatric COVID-19 occurrence or severity, (2) to determine changes in sACE levels over time, and (3) to investigate other factors associated with the occurrence and severity of pediatric COVID-19.…”

Targeting SARS-CoV-2 and host cell receptor interactions

“…Long-lasting, passive protection was achieved suggesting such an approach could be used to treat COVID-19 patients. On the other hand, high plasma level of sACE2s is often observed in COVID-19 patients with severe illness and increases with age ( Akin et al, 2022 ; Wissing et al, 2022 ), raising questions on whether sACE2 therapy will be beneficial to these patients.…”

COVID‐19 and preeclampsia: The unique and the mutually nonexclusive clinical manifestations

“…It has also been reported that sACE2 has also been used as a prognostic marker for the severity of the disease. Higher the level of sACE2, more severe is the disease 26,27 …”