Plasma ACE2 levels declined and ACE levels increased progressively with increasing COVID-19 severity, resulting in an elevated ACE/ACE2 ratio that indicates a pro-inflammatory shift.
Cohort (n=224)
In patients with COVID-19, increasing disease severity is associated with a progressive shift toward the pro-inflammatory arm of the renin-angiotensin system, characterized by increased ACE and decreased ACE2 levels.
Objective: The COVID-19 pandemic has strained healthcare systems and has been associated with substantial morbidity and mortality. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) enters host cells by binding to angiotensin-converting enzyme 2 (ACE2), implicating dysregulation of the renin–angiotensin system (RAS) in COVID-19 pathophysiology. Measurement of circulating RAS components, including ACE and ACE2, may therefore provide an insight into disease severity and underlying mechanisms. Subjects and Methods: In this retrospective cohort study, 224 adults with PCR-confirmed COVID-19 were stratified by World Health Organization disease-severity criteria into asymptomatic, mild, mild-pneumonia, severe, and critical groups. Plasma ACE and ACE2 concentrations were quantified by ELISA. Demographic, clinical, and laboratory data were extracted from electronic medical records. Results and Conclusions: Increasing disease severity was associated with higher mortality, elevated body mass index, and higher viral load estimates. Severe and critical illness was characterized by leukocytosis with neutrophilia, marked lymphopenia, anemia, elevated inflammatory and coagulation markers, renal dysfunction, and hypoalbuminemia. Plasma ACE2 levels declined progressively with increasing severity and were significantly lower in patients with mild-pneumonia, severe, or critical illness compared with asymptomatic or mild cases, showing a strong inverse correlation with severity. In contrast, plasma ACE levels increased significantly with disease severity. The resulting increase in the ACE/ACE2 ratio indicates a progressive shift toward the pro-inflammatory arm of the RAS, providing mechanistic insight into the COVID-19 pathophysiology.
Öz et al. (2026) conducted a cohort in COVID-19 (n=224). COVID-19 severity (mild-pneumonia, severe, critical) vs. Asymptomatic or mild COVID-19 was evaluated on Plasma ACE and ACE2 concentrations. Plasma ACE2 levels declined and ACE levels increased progressively with increasing COVID-19 severity, resulting in an elevated ACE/ACE2 ratio that indicates a pro-inflammatory shift.