ArticleResearch and practice in thrombosis and haemostasis2020
COVID-19 hypothesis: Activated protein C for therapy of virus-induced pathologic thromboinflammation.
Article in Research and practice in thrombosis and haemostasis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Immunothrombosis in Acute Respiratory Dysfunction of COVID-19.Frontiers in immunologyPooled it
- COVID-19 as a Modifier of Genetically Determined Coagulation Phenotype: Implications for Precision Risk Stratification After Infection.Biochemical genetics · 2026Observational
- Circulating Microclots Are Structurally Associated With Neutrophil Extracellular Traps and Their Amounts Are Elevated in Long COVID Patients.Journal of medical virology · 2025Article
- Time series differences in coagulopathy in mechanically ventilated COVID-19 and bacterial pneumonia patients: a nationwide observational study in Japan.Thrombosis journal · 2025Article
- Article
- Mechanisms of endothelial activation, hypercoagulation and thrombosis in COVID-19: a link with diabetes mellitus.Cardiovascular diabetology · 2024Review
- Understanding COVID-19-associated coagulopathy.Nature reviews. Immunology · 2022Review
- A Web Application for Biomedical Text Mining of Scientific Literature Associated with Coronavirus-Related Syndromes: Coronavirus Finder.Diagnostics (Basel, Switzerland) · 2022Article
- Neutrophil Extracellular Traps (NETs) and Covid-19: A new frontiers for therapeutic modality.International immunopharmacology · 2022Review
- Article
- Exploring the pathways of inflammation and coagulopathy in COVID-19: A narrative tour into a viral rabbit hole.International reviews of immunology · 2022Review
- Successful endovascular mechanical thrombectomy in anticoagulation-resistant COVID-19 associated cerebral venous sinus thrombosis.BMJ case reports · 2021Article
- Inflammation and thrombosis in COVID-19 pathophysiology: proteinase-activated and purinergic receptors as drivers and candidate therapeutic targets.Physiological reviews · 2021Review
- Large-Scale Multi-omic Analysis of COVID-19 Severity.Cell systems · 2021Article
- Commonalities Between COVID-19 and Radiation Injury.Radiation research · 2021Review
- Stroke, Research and Science in the Time of COVID.Stroke · 2020Article
- Large-scale Multi-omic Analysis of COVID-19 Severity.medRxiv : the preprint server for health sciences · 2020Article
- Coagulation Disorders in COVID-19: Role of Toll-like Receptors.Journal of inflammation research · 2020Review
- Stabilizing Cellular Barriers: Raising the Shields Against COVID-19.Frontiers in endocrinologyReview
- Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Seriously ill patients with coronavirus disease 2019 (COVID-19) at risk for death exhibit elevated cytokine and chemokine levels and D-dimer, and they often have comorbidities related to vascular dysfunctions. In preclinical studies, activated protein C (APC) provides negative feedback downregulation of excessive inflammation and thrombin generation, attenuates damage caused by ischemia-reperfusion in many organs including lungs, and reduces death caused by bacterial pneumonia. APC exerts both anticoagulant activities and direct cell-signaling activities. Preclinical studies show that its direct cell-signaling actions mediate anti-inflammatory and anti-apoptotic actions, mortality reduction for pneumonia, and beneficial actions for ischemia-reperfusion injury. The APC mutant 3K3A-APC, which was engineered to have diminished anticoagulant activity while retaining cell-signaling actions, was safe in phase 1 and phase 2 human trials. Because of its broad spectrum of homeostatic effects in preclinical studies, we speculate that 3K3A-APC merits consideration for clinical trial studies in appropriately chosen, seriously ill patients with 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.