ArticleBlood advances2022
Lymphatic coagulation and neutrophil extracellular traps in lung-draining lymph nodes of COVID-19 decedents.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Safeguarding lymphatic identity: cooperative Erg and Fli1 activity in lymphatic vascular homeostasis.The Journal of clinical investigation · 2026Article
- Lung Lymphatics in Edema, Inflammation, and Thrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Role of the Chest Wall in Newborn Respiratory Function at Birth.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Collecting lymphatics unzip to drain injured lungs.Nature cardiovascular research · 2025Article
- From defense to disease: the multifaceted role of lymphatics during infection.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- The thrombin receptor PAR1 orchestrates changes in lymphatic endothelial cell junction morphology to augment lymphatic drainage during lung injury.Nature cardiovascular research · 2025Article
- Article
- Meningeal lymphatic drainage: novel insights into central nervous system disease.Signal transduction and targeted therapy · 2025Review
- Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer.The Journal of experimental medicine · 2025Article
- Characterization of Neutrophil Functional Responses to SARS-CoV-2 Infection in a Translational Feline Model for COVID-19.International journal of molecular sciences · 2024Article
- Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer.bioRxiv : the preprint server for biology · 2024Article
- Neutrophil extracellular trap-mediated impairment of meningeal lymphatic drainage exacerbates secondary hydrocephalus after intraventricular hemorrhage.Theranostics · 2024Article
- Complement-Coagulation Cross-talk: Factor H-mediated regulation of the Complement Classical Pathway activation by fibrin clots.Frontiers in immunology · 2024Article
- Evaluating chest pain in patients with post COVID conditions permission to think outside of the box.Journal of thrombosis and thrombolysis · 2023Article
- Imaging peripheral lymphatic dysfunction in chronic conditions.Frontiers in physiology · 2023Review
Corrections and comments
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Authors and funding
20 authors at 1 institution in 1 country.
Funding
Abstract
Clinical manifestations of severe COVID-19 include coagulopathies that are exacerbated by the formation of neutrophil extracellular traps (NETs). Here, we report that pulmonary lymphatic vessels, which traffic neutrophils and other immune cells to the lung-draining lymph node (LDLN), can also be blocked by fibrin clots in severe COVID-19. Immunostained tissue sections from COVID-19 decedents revealed widespread lymphatic clotting not only in the lung but also in the LDLN, where the extent of clotting correlated with the presence of abnormal, regressed, or missing germinal centers (GCs). It strongly correlated with the presence of intralymphatic NETs. In mice, tumor necrosis factor α induced intralymphatic fibrin clots; this could be inhibited by DNase I, which degrades NETs. In vitro, TNF-α induced lymphatic endothelial cell upregulation of ICAM-1 and CXCL8, among other neutrophil-recruiting factors, as well as thrombomodulin downregulation; in decedents, lymphatic clotting in LDLNs. In a separate cohort of hospitalized patients, serum levels of Myeloperoxidase-DNA (MPO-DNA, a NET marker) inversely correlated with antiviral antibody titers, but D-dimer levels, indicative of blood thrombosis, did not correlate with either. Patients with high MPO-DNA but low D-dimer levels generated poor antiviral antibody titers. This study introduces lymphatic coagulation in lungs and LDLNs as a clinical manifestation of severe COVID-19 and suggests the involvement of NETosis of lymphatic-trafficking neutrophils. It further suggests that lymphatic clotting may correlate with impaired formation or maintenance of GCs necessary for robust antiviral antibody responses, although further studies are needed to determine whether and how lymphatic coagulation affects adaptive immune responses.
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