ReviewPhysiological reviews2021
Inflammation and thrombosis in COVID-19 pathophysiology: proteinase-activated and purinergic receptors as drivers and candidate therapeutic targets.
Review in Physiological reviews, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
57 citing papers in PubMed, 3 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- Accuracy of routine laboratory tests to predict mortality and deterioration to severe or critical COVID-19 in people with SARS-CoV-2.The Cochrane database of systematic reviews · 2024Pooled it
- Efficacy and safety of recanalization therapy for acute ischemic stroke with COVID-19: A systematic review and meta-analysis.Frontiers in neurology · 2022Pooled it
- COVID-19-Associated acute respiratory distress syndrome (CARDS): Mechanistic insights on therapeutic intervention and emerging trends.International immunopharmacology · 2021Pooled it
- Decreased serum levels of the inflammaging marker miR-146a are associated with clinical non-response to tocilizumab in COVID-19 patients.Mechanisms of ageing and development · 2021Trial
- PD0325901 alleviates thrombin-inhibited osteogenic differentiation through an IL-1β-activated feedback loop between MEK-Erk1/2 and NF-κB signal pathways: insights from bioinformatics and experimental verification.Frontiers in immunology · 2026Article
- Diagnostic biomarkers and immune infiltration profiles common to COVID-19, acute myocardial infarction and acute ischaemic stroke using bioinformatics methods and machine learning.BMC neurology · 2025Article
- Comprehensive insights into potential roles of purinergic P2 receptors on diseases: Signaling pathways involved and potential therapeutics.Journal of advanced research · 2025Review
- Unravelling the impact of SARS-CoV-2 on hemostatic and complement systems: a systems immunology perspective.Frontiers in immunology · 2024Article
- Gold single atom-based aptananozyme as an ultrasensitive and selective colorimetric probe for detection of thrombin and C-reactive protein.Mikrochimica acta · 2023Article
- Elevated CD39+T-Regulatory Cells and Reduced Levels of Adenosine Indicate a Role for Tolerogenic Signals in the Progression from Moderate to Severe COVID-19.International journal of molecular sciences · 2023Article
- Purinergic signaling: decoding its role in COVID-19 pathogenesis and promising treatment strategies.Inflammopharmacology · 2023Review
- The role of the endothelium in severe acute respiratory syndrome coronavirus 2 infection and pathogenesis.Current opinion in physiology · 2023Review
- Review
- Effect of colchicine and aspirin given together in patients with moderate COVID-19.Contemporary clinical trials communications · 2023Article
- The SARS-CoV-2 Spike Protein Activates the Epidermal Growth Factor Receptor-Mediated Signaling.Vaccines · 2023Article
- Inflammation Related to Association of Low Uric Acid and Progression to Severe Disease in Patients Hospitalized for Non-Severe Coronavirus Disease 2019.Biomedicines · 2023Article
- Effectiveness of thromboprophylaxis with low molecular weight heparin in critically ill patients with COVID-19. An observational prospective, multicenter study.Revista espanola de anestesiologia y reanimacion · 2023Observational
- Therapeutic Potential of the Purinergic System in Major Depressive Disorder Associated with COVID-19.Cellular and molecular neurobiology · 2023Review
- [Effectiveness of thromboprophylaxis with low molecular weight heparin in critically ill patients with COVID-19. An observational prospective, multicenter study].Revista espanola de anestesiologia y reanimacion · 2023Article
- Plasminogen activator inhibitor 1 is not a major causative factor for exacerbation in a mouse model of SARS-CoV-2 infection.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Evolving information has identified disease mechanisms and dysregulation of host biology that might be targeted therapeutically in coronavirus disease 2019 (COVID-19). Thrombosis and coagulopathy, associated with pulmonary injury and inflammation, are emerging clinical features of COVID-19. We present a framework for mechanisms of thrombosis in COVID-19 that initially derive from interaction of SARS-CoV-2 with ACE2, resulting in dysregulation of angiotensin signaling and subsequent inflammation and tissue injury. These responses result in increased signaling by thrombin (proteinase-activated) and purinergic receptors, which promote platelet activation and exert pathological effects on other cell types (e.g., endothelial cells, epithelial cells, and fibroblasts), further enhancing inflammation and injury. Inhibitors of thrombin and purinergic receptors may, thus, have therapeutic effects by blunting platelet-mediated thromboinflammation and dysfunction in other cell types. Such inhibitors include agents (e.g., anti-platelet drugs) approved for other indications, and that could be repurposed to treat, and potentially improve the outcome of, COVID-19 patients. COVID-19, caused by the SARS-CoV-2 virus, drives dysregulation of angiotensin signaling, which, in turn, increases thrombin-mediated and purinergic-mediated activation of platelets and increase in inflammation. This thromboinflammation impacts the lungs and can also have systemic effects. Inhibitors of receptors that drive platelet activation or inhibitors of the coagulation cascade provide opportunities to treat COVID-19 thromboinflammation.
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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.