ArticleNature communications2021
COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 3 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
74 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway.Journal of translational medicine · 2023Pooled it
- Genetic polymorphisms associated with susceptibility to COVID-19 disease and severity: A systematic review and meta-analysis.PloS one · 2022Pooled it
- Pooled it
- Trial
- The effect of TRV027 on coagulation in COVID-19: A pilot randomized, placebo-controlled trial.British journal of clinical pharmacology · 2023Trial
- Naturally occurring ACE2 stalk variants are differentially released from the cell.Scientific reports · 2026Article
- Naturally occurring ACE2 stalk variants are differentially released from the cell.bioRxiv : the preprint server for biology · 2026Article
- 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
- Extracellular-to-total body water ratio is associated with comorbidity and cardiorespiratory fitness in older adults with post-COVID-19 syndrome.Frontiers in nutrition · 2026Article
- Early clinical and laboratory markers associated with post-COVID respiratory syndrome: A retrospective analysis.PloS one · 2026Article
- Mechanisms and impact of long COVID: pathophysiology, neuropsychiatric effects and vaccination.Frontiers in immunology · 2026Review
- Targeting PTP4A3 with KVX-053 mitigates alcohol-amplified SARS-CoV-2 spike protein-induced acute lung injury.Frontiers in pharmacology · 2026Article
- Deep learning-driven proteomics analysis for gene annotation in the renin-angiotensin system.European journal of pharmacology · 2025Article
- SARS-CoV-2 infection disrupts syncytial and endothelial integrity and alters PlGF levels in the placenta.Placenta · 2025Article
- Severe acute respiratory syndrome coronavirus 2-mediated dysregulation of drug processing genes is dependent on pathogenic variants, target site of infection, age, and sex.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Effects and regulation of ACE2 and TMPRSS2 abundance in healthy humans and in patients with SARS-CoV-2.Biochemical Society transactions · 2025Article
- ALBACOVIDIOL Study: Effect of Calcifediol Treatment on Mortality in Patients Hospitalized for COVID-19: A Retrospective Analysis.Nutrients · 2025Observational
- Angiotensin converting enzyme 2 in patients with sepsis associate with comorbidities but neither with mortality nor with organ failure.Scientific reports · 2025Observational
- Acute aortic dissection-induced acute respiratory distress syndrome: pathogenesis and clinical implications.Frontiers in cardiovascular medicine · 2025Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.