ReviewEBioMedicine2020
The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19).
Review in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 2 syntheses or guidelines pooled it, 150 citations in OpenAlex.
- Recent Update on the Anti-Inflammatory Activities of Propolis.Molecules (Basel, Switzerland) · 2022Pooled it
- Synthesis and systematic review of reported neonatal SARS-CoV-2 infections.Nature communications · 2020Pooled it
- Pathophysiology of COVID-19: A Post Hoc Analysis of the ICAT-COVID Clinical Trial of the Bradykinin Antagonist Icatibant.Pathogens (Basel, Switzerland) · 2025Trial
- Inflammatory and Endothelial Dysfunction Biomarkers Predict Severe COVID-19 in Hospitalized Patients: Development of the CCBR Model.Biomedicines · 2026Article
- Bridge to transplant using a flow-adaptive extracorporeal total artificial lung system following bilateral pneumonectomy.Med (New York, N.Y.) · 2026Article
- Multi-omics identifies oxidative stress, prothrombotic pathways, and lactoperoxidase variants as key factors in COVID-19 severity.EBioMedicine · 2026Article
- Development and Clinical Validation of a Skin Test for In Vivo Assessment of SARS-CoV-2 Specific T-Cell Immunity.Viruses · 2025Article
- 3,3'-Diindolylmethane Improves the Viral Pneumonia Outcomes After Influenza and SARS-CoV-2 Infection in Animal Models.Viruses · 2025Article
- Investigation of the effect of serum gasdermin d levels on clinical course and mortality in patients with covid-19.BMC infectious diseases · 2025Observational
- Role of intravenous vitamin C on outcomes in hospitalized patients with moderate or severe COVID-19: a real life data of Turkish patients.Inflammopharmacology · 2025Article
- The Role of ACE2 in Neurological Disorders: From Underlying Mechanisms to the Neurological Impact of COVID-19.International journal of molecular sciences · 2024Review
- Pneumomediastinum and pneumoretroperitoneum after COVID-19: concealed intestinal perforation.BMC infectious diseases · 2024Article
- Acquired Immune Deficiency Syndrome correlation with SARS-CoV-2 N genotypes.Biomedical journal · 2024Article
- Immunoglobulins in COVID-19 pneumonia: from the acute phase to the recovery phase.European journal of medical research · 2024Article
- Potential marker subset of blood-circulating cytokines on hematopoietic progenitor-to-Th1 pathway in COVID-19.Frontiers in medicine · 2024Article
- Staying Ahead of the Game: How SARS-CoV-2 has Accelerated the Application of Machine Learning in Pandemic Management.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Serum Total Antioxidant Capacity (TAC) and TAC/Lymphocyte Ratio as Promising Predictive Markers in COVID-19.International journal of molecular sciences · 2023Article
- Impact of the SARS-CoV-2 nucleocapsid 203K/204R mutations on the inflammatory immune response in COVID-19 severity.Genome medicine · 2023Article
- Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases.Cell communication and signaling : CCS · 2023Review
- Inflammatory Response in COVID-19 Depending on the Severity of the Disease and the Vaccination Status.International journal of molecular sciences · 2023Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pathogenesis of coronavirus disease 2019 (COVID-19) may be envisaged as the dynamic interaction between four vicious feedback loops chained or happening at once. These are the viral loop, the hyperinflammatory loop, the non-canonical renin-angiotensin system (RAS) axis loop, and the hypercoagulation loop. Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1-7)/Mas1R axis. The viral feedback loop includes evading the host's innate response, uncontrolled viral replication, and turning on a hyperactive adaptative immune response. The inflammatory loop is composed of the exuberant inflammatory response feeding back until exploding in an actual cytokine storm. Downregulation of the ACE2/Ang-(1-7)/Mas1R axis leaves the lung without a critical defense mechanism and turns the scale to the inflammatory side of the RAS. The coagulation loop is a hypercoagulable state caused by the interplay between inflammation and coagulation in an endless feedback loop. The result is a hyperinflammatory and hypercoagulable state producing acute immune-mediated lung injury and eventually, adult respiratory distress syndrome.
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Registered trials
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.