ArticleBlood2021
SARS-CoV-2 infection induces the activation of tissue factor-mediated coagulation via activation of acid sphingomyelinase.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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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
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Tissue factor in COVID-19-associated coagulopathy.Thrombosis research · 2022Pooled it
- COVID-19 Vasculitis and vasculopathy-Distinct immunopathology emerging from the close juxtaposition of Type II Pneumocytes and Pulmonary Endothelial Cells.Seminars in immunopathology · 2022Pooled it
- Behind the membranous curtain-lipid dynamics and functions in coronaviral replication.Journal of virology · 2026Review
- Blood Coagulation in COVID-19: Systems-Biology Evidence, Clinical Implications, and Therapeutic Opportunities in an Evolving Pandemic.ACS omega · 2026Article
- Plasma Ceramides Levels in Severe COVID-19 Disease: Correlations with Survival.Open forum infectious diseases · 2026Article
- Article
- Assessing the endothelium's role in COVID-19 severity using the HUVEC model.Frontiers in immunology · 2025Article
- Viral Infection and Ischemic Stroke: Emerging Trends and Mechanistic Insights.Journal of the American Heart Association · 2024Review
- Monocyte-Mediated Thrombosis Linked to Circulating Tissue Factor and Immune Paralysis in COVID-19.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- The Proteome of Extracellular Vesicles Released from Pulmonary Microvascular Endothelium Reveals Impact of Oxygen Conditions on Biotrauma.International journal of molecular sciences · 2024Article
- Understanding COVID-19-associated endothelial dysfunction: role of PIEZO1 as a potential therapeutic target.Frontiers in immunology · 2024Review
- Metabolic alterations upon SARS-CoV-2 infection and potential therapeutic targets against coronavirus infection.Signal transduction and targeted therapy · 2023Review
- Peripheral blood mononuclear cell tissue factor (F3 gene) transcript levels and circulating extracellular vesicles are elevated in severe coronavirus 2019 (COVID-19) disease.Journal of thrombosis and haemostasis : JTH · 2023Article
- Extracellular Vesicles: New Players in the Mechanisms of Sepsis- and COVID-19-Related Thromboinflammation.International journal of molecular sciences · 2023Review
- Acute to post-acute COVID-19 thromboinflammation persistence: Mechanisms and potential consequences.Current research in immunology · 2023Review
- Tissue factor in cancer-associated thromboembolism: possible mechanisms and clinical applications.British journal of cancer · 2022Review
- TFPI and FXIII negatively and S100A8/A9 and Cystatin C positively correlate with D-dimer in COVID-19.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Risk stratification of patients with SARS-CoV-2 by tissue factor expression in circulating extracellular vesicles.Vascular pharmacology · 2022Article
- The interplay between inflammation and thrombosis in COVID-19: Mechanisms, therapeutic strategies, and challenges.Thrombosis update · 2022Review
- Platelet activation by SARS-CoV-2 implicates the release of active tissue factor by infected cells.Blood advances · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with the hypercoagulable state. Tissue factor (TF) is the primary cellular initiator of coagulation. Most of the TF expressed on cell surfaces remains cryptic. Sphingomyelin (SM) is responsible for maintaining TF in the encrypted state, and hydrolysis of SM by acid sphingomyelinase (ASMase) increases TF activity. ASMase was shown to play a role in virus infection biology. In the present study, we investigated the role of ASMase in SARS-CoV-2 infection-induced TF procoagulant activity. Infection of human monocyte-derived macrophages (MDMs) with SARS-CoV-2 spike protein pseudovirus (SARS-CoV-2-SP-PV) markedly increased TF procoagulant activity at the cell surface and released TF+ extracellular vesicles. The pseudovirus infection did not increase either TF protein expression or phosphatidylserine externalization. SARS-CoV-2-SP-PV infection induced the translocation of ASMase to the outer leaflet of the plasma membrane, which led to the hydrolysis of SM in the membrane. Pharmacologic inhibitors or genetic silencing of ASMase attenuated SARS-CoV-2-SP-PV-induced increased TF activity. Inhibition of the SARS-CoV-2 receptor, angiotensin-converting enzyme-2, attenuated SARS-CoV-2-SP-PV-induced increased TF activity. Overall, our data suggest that SARS-CoV-2 infection activates the coagulation by decrypting TF through activation of ASMase. Our data suggest that the US Food and Drug Administration-approved functional inhibitors of ASMase may help treat hypercoagulability in 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.