ReviewCell death and differentiation2020
An aberrant STAT pathway is central to COVID-19.
Review in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 3 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
189 citing papers in PubMed, 3 syntheses or guidelines pooled it, 305 citations in OpenAlex.
- Results of a systematic review and meta-analysis of early studies on ivermectin in SARS-CoV-2 infection.GeroScience · 2023Pooled it
- Role of the MicroRNAs in the Pathogenic Mechanism of Painful Symptoms in Long COVID: Systematic Review.International journal of molecular sciences · 2023Pooled it
- Immunomodulation as Treatment for Severe Coronavirus Disease 2019: A Systematic Review of Current Modalities and Future Directions.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Pooled it
- Neutrophils promote endothelial cell activation in pediatric Mycoplasma pneumoniae pneumonia.JCI insight · 2026Article
- Beyond Acute EGFR Blockade: Biological Basis and Clinical Evidence for Long-Term Nimotuzumab Therapy.Biomedicines · 2026Review
- Article
- DNA methylation profiles at hospital admission are associated with subsequent severe COVID-19 outcomes.Clinical epigenetics · 2026Article
- Pathogenic breaches: how viruses compromise blood-tissue barriers.Tissue barriers · 2026Review
- Rewired type I IFN signaling is linked to age-dependent differences in COVID-19.Cell reports. Medicine · 2025Article
- SOCS Proteins: Key Players in Immune Regulation During SARS-CoV-2 Infection.European journal of immunology · 2025Review
- ALBACOVIDIOL Study: Effect of Calcifediol Treatment on Mortality in Patients Hospitalized for COVID-19: A Retrospective Analysis.Nutrients · 2025Observational
- Mucosal implications of oral Jak3-targeted drugs in COVID patients.Molecular medicine (Cambridge, Mass.) · 2025Review
- Lyophilized MSC-EVs attenuates COVID-19 pathogenesis by regulating the JAK/STAT pathway.Stem cell research & therapy · 2025Article
- Impact of pH-Responsive Cisplatin/Ribavirin-Loaded Monodispersed Magnetic Silica Nanocomposite on A549 Lung Cancer Cells.Pharmaceutics · 2025Article
- Analysis of Stratifin Expression and Proteome Variation in a Rat Model of Acute Lung Injury.Journal of proteome research · 2025Article
- Identification ofMolecules (Basel, Switzerland) · 2025Article
- Dynamic Gene Attention Focus (DyGAF): Enhancing Biomarker Identification Through Dual-Model Attention Networks.Bioinformatics and biology insights · 2025Article
- Classification and regulatory interactions of key transcription factors in COVID-19.Frontiers in cellular and infection microbiology · 2025Review
- SARS-CoV-2 spike protein induces salivary gland dysfunction and immune infiltration in C57BL/6 mice.Frontiers in immunology · 2025Article
- Low-Grade Inflammation in Long COVID Syndrome Sustains a Persistent Platelet Activation Associated With Lung Impairment.JACC. Basic to translational science · 2025Article
129 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
5 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
COVID-19 is caused by SARS-CoV-2 infection and characterized by diverse clinical symptoms. Type I interferon (IFN-I) production is impaired and severe cases lead to ARDS and widespread coagulopathy. We propose that COVID-19 pathophysiology is initiated by SARS-CoV-2 gene products, the NSP1 and ORF6 proteins, leading to a catastrophic cascade of failures. These viral components induce signal transducer and activator of transcription 1 (STAT1) dysfunction and compensatory hyperactivation of STAT3. In SARS-CoV-2-infected cells, a positive feedback loop established between STAT3 and plasminogen activator inhibitor-1 (PAI-1) may lead to an escalating cycle of activation in common with the interdependent signaling networks affected in COVID-19. Specifically, PAI-1 upregulation leads to coagulopathy characterized by intravascular thrombi. Overproduced PAI-1 binds to TLR4 on macrophages, inducing the secretion of proinflammatory cytokines and chemokines. The recruitment and subsequent activation of innate immune cells within an infected lung drives the destruction of lung architecture, which leads to the infection of regional endothelial cells and produces a hypoxic environment that further stimulates PAI-1 production. Acute lung injury also activates EGFR and leads to the phosphorylation of STAT3. COVID-19 patients' autopsies frequently exhibit diffuse alveolar damage (DAD) and increased hyaluronan (HA) production which also leads to higher levels of PAI-1. COVID-19 risk factors are consistent with this scenario, as PAI-1 levels are increased in hypertension, obesity, diabetes, cardiovascular diseases, and old age. We discuss the possibility of using various approved drugs, or drugs currently in clinical development, to treat COVID-19. This perspective suggests to enhance STAT1 activity and/or inhibit STAT3 functions for COVID-19 treatment. This might derail the escalating STAT3/PAI-1 cycle central to COVID-19.
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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.