COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system
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Abstract
Abstract SARS-CoV-2 enters the cell through the ACE2 receptor, which is considered one of the main inhibitors in the Renin-Angiotensin-Aldosterone System (RAAS).1 ,2 The virus has been shown to downregulate the ACE2 receptor, leading to a subsequent increase in the vasopressoragentangiotensinII.3 Evidently,criticalcoronavirusdisease2019(COVID-19)is thought to be due to a dysregulated immune response, causing a cytokine-release syndrome eventually leading to acute respiratory distress syndrome (ARDS).4 ,5 However, several reports on clinical laboratory features and case-descriptions of critically ill patients with COVID-19 show discrepancies compared to typical ARDS. Here, we show that infusing swines with angiotensin II induces a pathophysiological syndrome closely resembling that of patients with RT-PCR-positive COVID-19. By using multimodal clinical imaging of patients, comparing laboratory data and translational histological features, we show that it is highly likely that an increase in RAAS is one, if not the main, pathogenic feature in critical COVID-19. Furthermore, it is plausible that this large animal model can be used to screen for potential new treatments for patients with severe COVID-19 and that MRI lung perfusion can be used to evaluate the outcome of potential treatments targeting the pathophysiological syndrome.
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Increased angiotensin-II levels and reduced angiotensin-(1-7) production due to lower ACE2 activity could provoke multiple COVID-19 symptoms, including vasoconstriction, thrombosis, inflammation, and potentially fatal respiratory failure.
“Increased levels of Ang-II and reduced production of Ang-1-7 due to the lower ACE2 activity could provoke multiple COVID-19 symptoms, including vasoconstriction, thrombosis, inflammation, and potentially fatal respiratory failure.14,18, 19, 20, 21”
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Preeclampsia in the Context of COVID‐19: Mechanisms, Pathophysiology, and Clinical Outcomes
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Losartan Inhibits SARS-CoV-2 Replication in Vitro
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The contribution of angiotensin peptides to cardiovascular neuroregulation in health and disease
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Calcifediol or Corticosteroids in the Treatment of COVID-19: An Observational Study
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Treatment with angiotensin II in COVID-19 patients may not be beneficial
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Deep learning-driven proteomics analysis for gene annotation in the renin-angiotensin system
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Cardiac involvement in patients 1 year after recovery from moderate and severe COVID-19 infections
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Losartan promotes cell survival following SARS-CoV-2 infection in vitroPreprint
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Abstracts from the 20th European symposium on radiopharmacy and radiopharmaceuticals
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Human Challenge Studies with Coronaviruses Old and New
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RetractedRodrigues, C. M., Santos, J. D., Garcia, B. C. C., Ottoni, M. H. F., Costa, K. B., Costa, M. L. B., Figueiredo, V. G., Macedo, D., de Oliveira, D. B., Vieira, E. R., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1729494 · Cited by 1 · see citing works
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Naturally occurring ACE2 stalk variants are differentially released from the cell
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A Case of Acute Pericarditis After COVID-19 Vaccination
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The Systemic Renin-Angiotensin System in COVID-19Preprint
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The Systemic Renin-Angiotensin System in COVID-19Preprint
Reindl‐Schwaighofer, R., Hödlmoser, S., Domenig, O., Krenn, K., Eskandary, F. A., Krenn, S., Schoergenhofer, C., Rumpf, B., Karolyi, M., Traugott, M. T., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1381017/v2
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Acute Vascular Injury in COVID-19
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Tratamientos y bioterapias para COVID-19
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Carotid body dysregulation contributes to the enigma of long COVIDPreprint
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Proteome profiling of nasopharynx reveals pathophysiological signature of COVID-19 disease severityPreprint
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The effect of pre-hospital use of RAS inhibitors on COVID-19 mortality
Ibrahim, R. (2024) · Journal of Investigative Medicine · doi:10.1177/10815589241270417
- Authors
- Rysz, S., Al-Saadi, J., Sjöström, A., Farm, M., Campoccia Jalde, F., Plattén, M., Eriksson, H., Klein, M., Vargas-Paris, R., Nyrén, S., Abdula, G., Ouellette, R., Granberg, T., Jonsson Fagerlund, M., & Lundberg, J.
- Affiliations
- Karolinska University Hospital (SE)
- Corresponding author
- Lundberg, Johan
- ORCID
- Venue
- Nature Communications
- Published
- 2021-04-23
- Volume
- 12
- Issue
- 1
- Pages
- 2417-2417
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC8065208
- OpenAlex
- W3152933878
- Cited by
- 111
- References
- 57
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 17 · 2023: 26 · 2022: 30 · 2021: 17 · 2020: 3
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Stockholm Region Clinical Post doc and ALF
- Stockholm Region Clinical Post Doc, Tedde Jeansson Sr and, MedTechLabs.
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- COVID-19 pandemic, SARS-CoV-2, renin-angiotensin-aldosterone system, ACE2, angiotensin II, pulmonary embolism, pulmonary artery pressure, pulmonary blood flow, coagulation, acute tubular necrosis, diffuse alveolar damage, angiotensin receptor blockers, low molecular weight heparin, porcine model, pathophysiology
- MeSH terms
- Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Angiotensin II, Animals, Female, Humans, Lung, Magnetic Resonance Imaging, Protein Binding, Renin-Angiotensin System, Retrospective Studies, Swine, Virus Internalization, Angiotensin Receptor Antagonists, Spike Glycoprotein, Coronavirus
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