ArticleScientific reports2022
The systemic renin-angiotensin system in COVID-19.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- COVID-19 and the Use of Angiotensin II Receptor Blockers in Older Chronic Hypertensive Patients: Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2023Pooled it
- Article
- COVID-19, the disease that changed the world.Medicine and pharmacy reports · 2026Review
- Renin-angiotensin system activation and oxidative stress in hospitalized COVID-19 patients: a single-centre prospective observational study.Intensive care medicine experimental · 2026Article
- Is long-term disruption of the renin-angiotensin-aldosterone system associated with long COVID? A retrospective cohort study among healthcare workers.BMC infectious diseases · 2026Article
- Roles of Reactive Oxygen Species in Relationships Between Viral Infections and Alzheimer's Disease and Related Dementia.Antioxidants (Basel, Switzerland) · 2026Review
- Assessment of Selected Biochemical Parameters of the Renin-Angiotensin-Aldosterone System in Repeat Convalescent Plasma Donors in the Context of Long-Term Changes Following SARS-CoV-2 Infection.Journal of clinical medicine · 2025Article
- Acute serum protein biomarker profile and prevalence of persistent (>6 months) neuropsychiatric symptoms in a cohort of SARS-CoV-2 PCR positive patients in Cape Town, South Africa.Brain, behavior, & immunity - health · 2025Article
- Naturally Occurring Angiotensin Peptides Enhance the SARS-CoV-2 Spike Protein Binding to Its Receptors.International journal of molecular sciences · 2025Article
- Integrated renin angiotensin system dysregulation and immune profiles predict COVID-19 disease severity in a South African cohort.Scientific reports · 2025Article
- Alterations in the renin-angiotensin system during septic shock.Annals of intensive care · 2025Article
- Mathematical modeling of impacts of patient differences on renin-angiotensin system and applications to COVID-19 lung fibrosis outcomes.Computers in biology and medicine · 2025Article
- Renin-angiotensin-aldosterone system activation in plasma as marker for prognosis in critically ill patients with COVID-19: a prospective exploratory study.Annals of intensive care · 2025Article
- Viral Infection and Ischemic Stroke: Emerging Trends and Mechanistic Insights.Journal of the American Heart Association · 2024Review
- Evaluation of angiotensin converting enzyme 2 (ACE2), angiotensin II (Ang II), miR-141-3p, and miR-421 levels in SARS-CoV-2 patients: a case-control study.BMC infectious diseases · 2024Article
- The Renin-Angiotensin System (RAS) in COVID-19 Disease: Where We Are 3 Years after the Beginning of the Pandemic.Microorganisms · 2024Review
- Intra- and postoperative relative angiotensin II deficiency in patients undergoing elective major abdominal surgery.Frontiers in endocrinology · 2024Observational
- Bioinformatic characterization of ENPEP, the gene encoding a potential cofactor for SARS-CoV-2 infection.PloS one · 2024Article
- Renin-angiotensin system inhibitor discontinuation in COVID-19 did not modify systemic ACE2 in a randomized controlled trial.iScience · 2023Article
- ACE2, ACE, DPPIV, PREP and CAT L enzymatic activities in COVID-19: imbalance of ACE2/ACE ratio and potential RAAS dysregulation in severe cases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
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Authors and funding
31 authors at 5 institutions in 1 country.
Funding
Abstract
SARS-CoV-2 gains cell entry via angiotensin-converting enzyme (ACE) 2, a membrane-bound enzyme of the "alternative" (alt) renin-angiotensin system (RAS). ACE2 counteracts angiotensin II by converting it to potentially protective angiotensin 1-7. Using mass spectrometry, we assessed key metabolites of the classical RAS (angiotensins I-II) and alt-RAS (angiotensins 1-7 and 1-5) pathways as well as ACE and ACE2 concentrations in 159 patients hospitalized with COVID-19, stratified by disease severity (severe, n = 76; non-severe: n = 83). Plasma renin activity (PRA-S) was calculated as the sum of RAS metabolites. We estimated ACE activity using the angiotensin II:I ratio (ACE-S) and estimated systemic alt-RAS activation using the ratio of alt-RAS axis metabolites to PRA-S (ALT-S). We applied mixed linear models to assess how PRA-S and ACE/ACE2 concentrations affected ALT-S, ACE-S, and angiotensins II and 1-7. Median angiotensin I and II levels were higher with severe versus non-severe COVID-19 (angiotensin I: 86 versus 30 pmol/L, p < 0.01; angiotensin II: 114 versus 58 pmol/L, p < 0.05), demonstrating activation of classical RAS. The difference disappeared with analysis limited to patients not taking a RAS inhibitor (angiotensin I: 40 versus 31 pmol/L, p = 0.251; angiotensin II: 76 versus 99 pmol/L, p = 0.833). ALT-S in severe COVID-19 increased with time (days 1-6: 0.12; days 11-16: 0.22) and correlated with ACE2 concentration (r = 0.831). ACE-S was lower in severe versus non-severe COVID-19 (1.6 versus 2.6; p < 0.001), but ACE concentrations were similar between groups and correlated weakly with ACE-S (r = 0.232). ACE2 and ACE-S trajectories in severe COVID-19, however, did not differ between survivors and non-survivors. Overall RAS alteration in severe COVID-19 resembled severity of disease-matched patients with influenza. In mixed linear models, renin activity most strongly predicted angiotensin II and 1-7 levels. ACE2 also predicted angiotensin 1-7 levels and ALT-S. No single factor or the combined model, however, could fully explain ACE-S. ACE2 and ACE-S trajectories in severe COVID-19 did not differ between survivors and non-survivors. In conclusion, angiotensin II was elevated in severe COVID-19 but was markedly influenced by RAS inhibitors and driven by overall RAS activation. ACE-S was significantly lower with severe COVID-19 and did not correlate with ACE concentrations. A shift to the alt-RAS axis because of increased ACE2 could partially explain the relative reduction in angiotensin II levels.
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