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Nature communications
03 05, 2021;12 (1): 1428.

Deciphering the state of immune silence in fatal COVID-19 patients.

Pierre Bost, Francesco De Sanctis, Stefania Canè, Stefano Ugel, Katia Donadello, Monica Castellucci, David Eyal, Alessandra Fiore, Cristina Anselmi, Roza Maria Barouni, Rosalinda Trovato, Simone Caligola, Alessia Lamolinara, Manuela Iezzi, Federica Facciotti, Annarita Mazzariol, Davide Gibellini, Pasquale De Nardo, Evelina Tacconelli, Leonardo Gottin, Enrico Polati, Benno Schwikowski, Ido Amit, Vincenzo Bronte
Author Information
  1. Pierre Bost: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
  2. Francesco De Sanctis: Immunology Section, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy.
  3. Stefania Canè: Immunology Section, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy.
  4. Stefano Ugel: Immunology Section, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy. ORCID
  5. Katia Donadello: Intensive Care Unit, Department of Surgery, Dentistry, Maternity and Infant, University and Hospital Trust of Verona, Verona, Italy.
  6. Monica Castellucci: The Center for Technological Platforms, University of Verona, Verona, Italy.
  7. David Eyal: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
  8. Alessandra Fiore: Immunology Section, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy.
  9. Cristina Anselmi: Immunology Section, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy.
  10. Roza Maria Barouni: Immunology Section, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy.
  11. Rosalinda Trovato: Immunology Section, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy.
  12. Simone Caligola: Immunology Section, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy. ORCID
  13. Alessia Lamolinara: CAST- Center for Advanced Studies and Technology, Department of Neurosciences, Imaging and Clinical Sciences, University of G. D'Annunzio of Chieti-Pescara, Chieti, Italy. ORCID
  14. Manuela Iezzi: CAST- Center for Advanced Studies and Technology, Department of Neurosciences, Imaging and Clinical Sciences, University of G. D'Annunzio of Chieti-Pescara, Chieti, Italy. ORCID
  15. Federica Facciotti: Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy. ORCID
  16. Annarita Mazzariol: Microbiology Unit, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy.
  17. Davide Gibellini: Microbiology Unit, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy.
  18. Pasquale De Nardo: Division of Infectious Diseases, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy.
  19. Evelina Tacconelli: Division of Infectious Diseases, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy.
  20. Leonardo Gottin: Intensive Care Unit, Department of Surgery, Dentistry, Maternity and Infant, University and Hospital Trust of Verona, Verona, Italy.
  21. Enrico Polati: Intensive Care Unit, Department of Surgery, Dentistry, Maternity and Infant, University and Hospital Trust of Verona, Verona, Italy.
  22. Benno Schwikowski: Systems Biology Group, Department of Computational Biology and USR 3756, Institut Pasteur and CNRS, Paris, France. ORCID
  23. Ido Amit: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. ido.amit@weizmann.ac.il. ORCID
  24. Vincenzo Bronte: Immunology Section, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy. vincenzo.bronte@univr.it. ORCID
PMID: 33674591 DOI: 10.1038/s41467-021-21702-6

Abstract

Since the beginning of the SARS-CoV-2 pandemic, COVID-19 appeared as a unique disease with unconventional tissue and systemic immune features. Here we show a COVID-19 immune signature associated with severity by integrating single-cell RNA-seq analysis from blood samples and broncho-alveolar lavage fluids with clinical, immunological and functional ex vivo data. This signature is characterized by lung accumulation of naïve lymphoid cells associated with a systemic expansion and activation of myeloid cells. Myeloid-driven immune suppression is a hallmark of COVID-19 evolution, highlighting arginase-1 expression with immune regulatory features of monocytes. Monocyte-dependent and neutrophil-dependent immune suppression loss is associated with fatal clinical outcome in severe patients. Additionally, our analysis shows a lung CXCR6 effector memory T cell subset is associated with better prognosis in patients with severe COVID-19. In summary, COVID-19-induced myeloid dysregulation and lymphoid impairment establish a condition of 'immune silence' in patients with critical COVID-19.

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Grants

  1. /Howard Hughes Medical Institute

MeSH Term

Aged
Aged, 80 and over
CD8-Positive T-Lymphocytes
COVID-19
Case-Control Studies
Cytokines
Female
Humans
Male
Middle Aged
Monocytes
Myeloid Cells
Neutrophils
SARS-CoV-2
T-Lymphocytes

Chemicals

Cytokines
Journal Article Research Support, Non-U.S. Gov't

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