Identification of natural killer markers associated with fatal outcome in COVID-19 patients
IntroductionIncreasing 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 analys...
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| Format: | Article |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1165756/full |
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| author | Nadine Tarantino Elena Litvinova Elena Litvinova Assia Samri Cathia Soulié Véronique Morin Alice Rousseau Karim Dorgham Christophe Parizot Olivia Bonduelle Alexandra Beurton Alexandra Beurton Makoto Miyara Makoto Miyara Pascale Ghillani Julien Mayaux Raphael Lhote Jean-Marc Lacorte Jean-Marc Lacorte Anne-Geneviève Marcelin Zahir Amoura Zahir Amoura Charles-Edouard Luyt Charles-Edouard Luyt Guy Gorochov Guy Gorochov Amélie Guihot Amélie Guihot Vincent Vieillard |
| author_facet | Nadine Tarantino Elena Litvinova Elena Litvinova Assia Samri Cathia Soulié Véronique Morin Alice Rousseau Karim Dorgham Christophe Parizot Olivia Bonduelle Alexandra Beurton Alexandra Beurton Makoto Miyara Makoto Miyara Pascale Ghillani Julien Mayaux Raphael Lhote Jean-Marc Lacorte Jean-Marc Lacorte Anne-Geneviève Marcelin Zahir Amoura Zahir Amoura Charles-Edouard Luyt Charles-Edouard Luyt Guy Gorochov Guy Gorochov Amélie Guihot Amélie Guihot Vincent Vieillard |
| author_sort | Nadine Tarantino |
| collection | DOAJ |
| description | IntroductionIncreasing 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.MethodsWe 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.ResultsHere, 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.DiscussionThese 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. |
| first_indexed | 2024-03-13T07:17:30Z |
| format | Article |
| id | doaj.art-d2455d1f075a4e8e82ac78227b02e211 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-03-13T07:17:30Z |
| publishDate | 2023-06-01 |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-d2455d1f075a4e8e82ac78227b02e2112023-06-05T05:07:17ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-06-011310.3389/fcimb.2023.11657561165756Identification of natural killer markers associated with fatal outcome in COVID-19 patientsNadine Tarantino0Elena Litvinova1Elena Litvinova2Assia Samri3Cathia Soulié4Véronique Morin5Alice Rousseau6Karim Dorgham7Christophe Parizot8Olivia Bonduelle9Alexandra Beurton10Alexandra Beurton11Makoto Miyara12Makoto Miyara13Pascale Ghillani14Julien Mayaux15Raphael Lhote16Jean-Marc Lacorte17Jean-Marc Lacorte18Anne-Geneviève Marcelin19Zahir Amoura20Zahir Amoura21Charles-Edouard Luyt22Charles-Edouard Luyt23Guy Gorochov24Guy Gorochov25Amélie Guihot26Amélie Guihot27Vincent Vieillard28Sorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, FranceSorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Département d’Immunologie, Paris, FranceSorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, FranceSorbonne 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, FranceSorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, FranceSorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, FranceSorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Département d’Immunologie, Paris, FranceSorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Service de Médecine Intensive-Réanimation et Pneumologie, Paris, FranceSorbonne Université, Inserm UMRS Neurophysiologie Respiratoire Expérimentale et Clinique, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, FranceSorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Département d’Immunologie, Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Département d’Immunologie, Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Service de Médecine Intensive-Réanimation et Pneumologie, Paris, FranceService de Médecine Interne 2, Institut E3M, Assistance Publique – Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Paris, FranceSorbonne Université, Inserm, UMRS1166-ICAN Institute of Cardiometabolism and Nutrition, Paris, FranceService de Biochimie Endocrinienne et Oncologique, Assistance Publique – Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Paris, FranceSorbonne 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, FranceSorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, FranceService de Médecine Interne 2, Institut E3M, Assistance Publique – Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Service de Médecine Intensive-Réanimation et Pneumologie, Paris, FranceService de Médecine Interne 2, Institut E3M, Assistance Publique – Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Paris, FranceSorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Département d’Immunologie, Paris, FranceSorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, FranceAssistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Département d’Immunologie, Paris, FranceSorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, FranceIntroductionIncreasing 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.MethodsWe 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.ResultsHere, 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.DiscussionThese 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.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1165756/fullfatal outcomeCOVID-19natural killer (Nk) cellSARS-CoV-2 infectiontNF-alpha |
| spellingShingle | Nadine Tarantino Elena Litvinova Elena Litvinova Assia Samri Cathia Soulié Véronique Morin Alice Rousseau Karim Dorgham Christophe Parizot Olivia Bonduelle Alexandra Beurton Alexandra Beurton Makoto Miyara Makoto Miyara Pascale Ghillani Julien Mayaux Raphael Lhote Jean-Marc Lacorte Jean-Marc Lacorte Anne-Geneviève Marcelin Zahir Amoura Zahir Amoura Charles-Edouard Luyt Charles-Edouard Luyt Guy Gorochov Guy Gorochov Amélie Guihot Amélie Guihot Vincent Vieillard Identification of natural killer markers associated with fatal outcome in COVID-19 patients Frontiers in Cellular and Infection Microbiology fatal outcome COVID-19 natural killer (Nk) cell SARS-CoV-2 infection tNF-alpha |
| title | Identification of natural killer markers associated with fatal outcome in COVID-19 patients |
| title_full | Identification of natural killer markers associated with fatal outcome in COVID-19 patients |
| title_fullStr | Identification of natural killer markers associated with fatal outcome in COVID-19 patients |
| title_full_unstemmed | Identification of natural killer markers associated with fatal outcome in COVID-19 patients |
| title_short | Identification of natural killer markers associated with fatal outcome in COVID-19 patients |
| title_sort | identification of natural killer markers associated with fatal outcome in covid 19 patients |
| topic | fatal outcome COVID-19 natural killer (Nk) cell SARS-CoV-2 infection tNF-alpha |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2023.1165756/full |
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