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Fibrin drives thromboinflammation and neuropathology in COVID-19.
Ryu, Jae Kyu; Yan, Zhaoqi; Montano, Mauricio; Sozmen, Elif G; Dixit, Karuna; Suryawanshi, Rahul K; Matsui, Yusuke; Helmy, Ekram; Kaushal, Prashant; Makanani, Sara K; Deerinck, Thomas J; Meyer-Franke, Anke; Rios Coronado, Pamela E; Trevino, Troy N; Shin, Min-Gyoung; Tognatta, Reshmi; Liu, Yixin; Schuck, Renaud; Le, Lucas; Miyajima, Hisao; Mendiola, Andrew S; Arun, Nikhita; Guo, Brandon; Taha, Taha Y; Agrawal, Ayushi; MacDonald, Eilidh; Aries, Oliver; Yan, Aaron; Weaver, Olivia; Petersen, Mark A; Meza Acevedo, Rosa; Alzamora, Maria Del Pilar S; Thomas, Reuben; Traglia, Michela; Kouznetsova, Valentina L; Tsigelny, Igor F; Pico, Alexander R; Red-Horse, Kristy; Ellisman, Mark H; Krogan, Nevan J; Bouhaddou, Mehdi; Ott, Melanie; Greene, Warner C; Akassoglou, Katerina.
Afiliación
  • Ryu JK; Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
  • Yan Z; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Montano M; Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
  • Sozmen EG; Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
  • Dixit K; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Suryawanshi RK; Gladstone Institute of Virology, San Francisco, CA, USA.
  • Matsui Y; Michael Hulton Center for HIV Cure Research at Gladstone, San Francisco, CA, USA.
  • Helmy E; Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
  • Kaushal P; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Makanani SK; Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
  • Deerinck TJ; Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
  • Meyer-Franke A; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Rios Coronado PE; Gladstone Institute of Virology, San Francisco, CA, USA.
  • Trevino TN; Gladstone Institute of Virology, San Francisco, CA, USA.
  • Shin MG; Michael Hulton Center for HIV Cure Research at Gladstone, San Francisco, CA, USA.
  • Tognatta R; Gladstone Institute of Virology, San Francisco, CA, USA.
  • Liu Y; Michael Hulton Center for HIV Cure Research at Gladstone, San Francisco, CA, USA.
  • Schuck R; Department of Microbiology, Immunology and Molecular Genetics (MIMG), University of California Los Angeles, Los Angeles, CA, USA.
  • Le L; Institute for Quantitative and Computational Biosciences (QCBio), University of California Los Angeles, Los Angeles, CA, USA.
  • Miyajima H; Department of Microbiology, Immunology and Molecular Genetics (MIMG), University of California Los Angeles, Los Angeles, CA, USA.
  • Mendiola AS; Institute for Quantitative and Computational Biosciences (QCBio), University of California Los Angeles, Los Angeles, CA, USA.
  • Arun N; National Center for Microscopy and Imaging Research, Center for Research on Biological Systems, University of California San Diego, La Jolla, CA, USA.
  • Guo B; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Taha TY; Department of Biology, Stanford University, Stanford, CA, USA.
  • Agrawal A; Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
  • MacDonald E; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Aries O; Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA.
  • Yan A; Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
  • Weaver O; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Petersen MA; Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
  • Meza Acevedo R; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Alzamora MDPS; Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
  • Thomas R; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Traglia M; Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
  • Kouznetsova VL; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Tsigelny IF; Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
  • Pico AR; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Red-Horse K; Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
  • Ellisman MH; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Krogan NJ; Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
  • Bouhaddou M; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Ott M; Center for Neurovascular Brain Immunology at Gladstone and UCSF, San Francisco, CA, USA.
  • Greene WC; Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Akassoglou K; Gladstone Institute of Virology, San Francisco, CA, USA.
Nature ; 2024 Aug 28.
Article en En | MEDLINE | ID: mdl-39198643
ABSTRACT
Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 and are persistent in patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection1-4. Despite the clinical evidence1,5-7, the underlying mechanisms of coagulopathy in COVID-19 and its consequences in inflammation and neuropathology remain poorly understood and treatment options are insufficient. Fibrinogen, the central structural component of blood clots, is abundantly deposited in the lungs and brains of patients with COVID-19, correlates with disease severity and is a predictive biomarker for post-COVID-19 cognitive deficits1,5,8-10. Here we show that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19. Fibrin, acting through its inflammatory domain, is required for oxidative stress and macrophage activation in the lungs, whereas it suppresses natural killer cells, after SARS-CoV-2 infection. Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection. A monoclonal antibody targeting the inflammatory fibrin domain provides protection from microglial activation and neuronal injury, as well as from thromboinflammation in the lung after infection. Thus, fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute COVID-19 and long COVID.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Nature Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos