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Frontiers in cellular and infection microbiology
2023;13 1165756.

Identification of natural killer markers associated with fatal outcome in COVID-19 patients.

Nadine Tarantino, Elena Litvinova, Assia Samri, Cathia Soulié, Véronique Morin, Alice Rousseau, Karim Dorgham, Christophe Parizot, Olivia Bonduelle, Alexandra Beurton, Makoto Miyara, Pascale Ghillani, Julien Mayaux, Raphael Lhote, Jean-Marc Lacorte, Anne-Geneviève Marcelin, Zahir Amoura, Charles-Edouard Luyt, Guy Gorochov, Amélie Guihot, Vincent Vieillard
Author Information
  1. Nadine Tarantino: Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France.
  2. Elena Litvinova: Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France.
  3. Assia Samri: Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France.
  4. Cathia Soulié: Sorbonne Université, Inserm, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Laboratoire de Virologie, Paris, France.
  5. Véronique Morin: Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France.
  6. Alice Rousseau: Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France.
  7. Karim Dorgham: Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France.
  8. Christophe Parizot: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Département d'Immunologie, Paris, France.
  9. Olivia Bonduelle: Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France.
  10. Alexandra Beurton: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Service de Médecine Intensive-Réanimation et Pneumologie, Paris, France.
  11. Makoto Miyara: Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France.
  12. Pascale Ghillani: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Département d'Immunologie, Paris, France.
  13. Julien Mayaux: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Service de Médecine Intensive-Réanimation et Pneumologie, Paris, France.
  14. Raphael Lhote: Service de Médecine Interne 2, Institut E3M, Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Paris, France.
  15. Jean-Marc Lacorte: Sorbonne Université, Inserm, UMRS1166-ICAN Institute of Cardiometabolism and Nutrition, Paris, France.
  16. Anne-Geneviève Marcelin: Sorbonne Université, Inserm, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Laboratoire de Virologie, Paris, France.
  17. Zahir Amoura: Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France.
  18. Charles-Edouard Luyt: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Service de Médecine Intensive-Réanimation et Pneumologie, Paris, France.
  19. Guy Gorochov: Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France.
  20. Amélie Guihot: Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France.
  21. Vincent Vieillard: Sorbonne Université, Inserm, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France.
PMID: 37342247 DOI: 10.3389/fcimb.2023.1165756

Abstract

Introduction: Increasing evidence has shown that coronavirus disease 19 (COVID-19) severity is driven by a dysregulated immunological response. Previous studies have demonstrated that natural killer (NK) cell dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of NK cell markers as a driver of death in the most critically ill patients.
Methods: We enrolled 50 non-vaccinated hospitalized patients infected with the initial virus or the alpha variant of SARS-CoV-2 with moderate or severe illness, to evaluate phenotypic and functional features of NK cells.
Results: Here, we show that, consistent with previous studies, evolution NK cells from COVID-19 patients are more activated, with the decreased activation of natural cytotoxicity receptors and impaired cytotoxicity and IFN-γ production, in association with disease regardless of the SARS-CoV-2 strain. Fatality was observed in 6 of 17 patients with severe disease; NK cells from all of these patients displayed a peculiar phenotype of an activated memory-like phenotype associated with massive TNF-α production.
Discussion: These data suggest that fatal COVID-19 infection is driven by an uncoordinated inflammatory response in part mediated by a specific subset of activated NK cells.

Keywords

COVID-19 SARS-CoV-2 infection fatal outcome natural killer (Nk) cell tNF-alpha

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MeSH Term

COVID-19
Humans
Killer Cells, Natural
SARS-CoV-2
Patient Acuity
Fatal Outcome
COVID-19 Vaccines
Male
Adult
Middle Aged
Aged
Aged, 80 and over
Receptors, Natural Killer Cell
Tumor Necrosis Factor-alpha
Lymphocyte Activation

Chemicals

COVID-19 Vaccines
Receptors, Natural Killer Cell
Tumor Necrosis Factor-alpha
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 2

Word Cloud

Created with Highcharts 10.0.0patientsCOVID-19NKnaturalcellsdiseasekillercellsevereSARS-CoV-2activatedfataldrivenresponsestudiesillnessmarkerscytotoxicityproductionphenotypeassociatedinfectionoutcomeIntroduction:Increasingevidenceshowncoronavirus19severitydysregulatedimmunologicalPreviousdemonstrateddysfunctionunderpinslackedin-depthanalysisdriverdeathcriticallyillMethods:enrolled50non-vaccinatedhospitalizedinfectedinitialvirusalphavariantmoderateevaluatephenotypicfunctionalfeaturesResults:showconsistentpreviousevolutiondecreasedactivationreceptorsimpairedIFN-γassociationregardlessstrainFatalityobserved617displayedpeculiarmemory-likemassiveTNF-αDiscussion:datasuggestuncoordinatedinflammatorypartmediatedspecificsubsetIdentificationNktNF-alpha

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