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Global absence and targeting of protective immune states in severe COVID-19.
Combes, Alexis J; Courau, Tristan; Kuhn, Nicholas F; Hu, Kenneth H; Ray, Arja; Chen, William S; Chew, Nayvin W; Cleary, Simon J; Kushnoor, Divyashree; Reeder, Gabriella C; Shen, Alan; Tsui, Jessica; Hiam-Galvez, Kamir J; Muñoz-Sandoval, Priscila; Zhu, Wandi S; Lee, David S; Sun, Yang; You, Ran; Magnen, Mélia; Rodriguez, Lauren; Im, K W; Serwas, Nina K; Leligdowicz, Aleksandra; Zamecnik, Colin R; Loudermilk, Rita P; Wilson, Michael R; Ye, Chun J; Fragiadakis, Gabriela K; Looney, Mark R; Chan, Vincent; Ward, Alyssa; Carrillo, Sidney; Matthay, Michael; Erle, David J; Woodruff, Prescott G; Langelier, Charles; Kangelaris, Kirsten; Hendrickson, Carolyn M; Calfee, Carolyn; Rao, Arjun Arkal; Krummel, Matthew F.
Afiliação
  • Combes AJ; Department of Pathology, University of California San Francisco, San Francisco, CA, USA. Alexis.Combes@ucsf.edu.
  • Courau T; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA. Alexis.Combes@ucsf.edu.
  • Kuhn NF; UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA. Alexis.Combes@ucsf.edu.
  • Hu KH; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  • Ray A; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Chen WS; UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Chew NW; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  • Cleary SJ; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Kushnoor D; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  • Reeder GC; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Shen A; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  • Tsui J; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Hiam-Galvez KJ; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Muñoz-Sandoval P; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Zhu WS; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  • Lee DS; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Sun Y; UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • You R; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Magnen M; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Rodriguez L; Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
  • Im KW; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  • Serwas NK; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Leligdowicz A; UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Zamecnik CR; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  • Loudermilk RP; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Wilson MR; UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Ye CJ; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  • Fragiadakis GK; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Looney MR; UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Chan V; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  • Ward A; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Carrillo S; UCSF CoLabs, University of California San Francisco, San Francisco, CA, USA.
  • Matthay M; Department of Otolaryngology, University of California San Francisco, San Francisco, CA, USA.
  • Erle DJ; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
  • Woodruff PG; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Langelier C; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
  • Kangelaris K; Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, CA, USA.
  • Hendrickson CM; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
  • Calfee C; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
  • Rao AA; Sandler Asthma Basic Research Center, University of California San Francisco, San Francisco, CA, USA.
  • Krummel MF; ImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
Nature ; 591(7848): 124-130, 2021 03.
Article em En | MEDLINE | ID: mdl-33494096
ABSTRACT
Although infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has pleiotropic and systemic effects in some individuals1-3, many others experience milder symptoms. Here, to gain a more comprehensive understanding of the distinction between severe and mild phenotypes in the pathology of coronavirus disease 2019 (COVID-19) and its origins, we performed a whole-blood-preserving single-cell analysis protocol to integrate contributions from all major immune cell types of the blood-including neutrophils, monocytes, platelets, lymphocytes and the contents of the serum. Patients with mild COVID-19 exhibit a coordinated pattern of expression of interferon-stimulated genes (ISGs)3 across every cell population, whereas these ISG-expressing cells are systemically absent in patients with severe disease. Paradoxically, individuals with severe COVID-19 produce very high titres of anti-SARS-CoV-2 antibodies and have a lower viral load compared to individuals with mild disease. Examination of the serum from patients with severe COVID-19 shows that these patients uniquely produce antibodies that functionally block the production of the ISG-expressing cells associated with mild disease, by activating conserved signalling circuits that dampen cellular responses to interferons. Overzealous antibody responses pit the immune system against itself in many patients with COVID-19, and perhaps also in individuals with other viral infections. Our findings reveal potential targets for immunotherapies in patients with severe COVID-19 to re-engage viral defence.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Interferons / SARS-CoV-2 / COVID-19 / Anticorpos Antivirais Limite: Female / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Interferons / SARS-CoV-2 / COVID-19 / Anticorpos Antivirais Limite: Female / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article