Distinct cytokine profiles associated with COVID-19 severity and mortality

Karim Dorgham; Paul Quentric; Mehmet Gökkaya; Stéphane Marot; Christophe Parizot; Delphine Sauce; Amélie Guihot; Charles Edouard Luyt; Matthieu Schmidt; Julien Mayaux; Alexandra Beurton; Loic Le Guennec; Sophie Demeret; Elyes Ben Salah; Alexis Mathian; Hans Yssel; Béhazine Combadiere; Christophe Combadiere; Claudia Traidl-Hoffmann; Sonia Burrel; Anne Geneviève Marcelin; Zahir Amoura; Guillaume Voiriot; Avidan U. Neumann; Guy Gorochov

doi:10.1016/j.jaci.2021.03.047

Distinct cytokine profiles associated with COVID-19 severity and mortality

Karim Dorgham
, Paul Quentric
, Mehmet Gökkaya
, Stéphane Marot
, Christophe Parizot
, Delphine Sauce
, Amélie Guihot
, Charles Edouard Luyt
, Matthieu Schmidt
, Julien Mayaux
, Alexandra Beurton
, Loic Le Guennec
, Sophie Demeret
, Elyes Ben Salah
, Alexis Mathian
, Hans Yssel
, Béhazine Combadiere
, Christophe Combadiere
, Claudia Traidl-Hoffmann
, Sonia Burrel

Anne Geneviève Marcelin, Zahir Amoura, Guillaume Voiriot, Avidan U. Neumann, Guy Gorochov

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

Abstract

Background: Markedly elevated levels of proinflammatory cytokines and defective type-I interferon responses were reported in patients with coronavirus disease 2019 (COVID-19). Objective: We sought to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. Methods: Cytokine concentrations and severe acute respiratory syndrome coronavirus 2 antigen were measured at hospital admission in serum of symptomatic patients with COVID-19 (N = 115), classified at hospitalization into 3 respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS), and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal-component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N = 86). Results: At time of hospitalization, ECMO patients presented a dominant proinflammatory response with elevated levels of TNF-α, IL-6, IL-8, and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-β was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at 1 month was associated with higher levels of proinflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients, and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (risk ratio, 24.3; P <.0001). Severe acute respiratory syndrome coronavirus 2 antigen levels correlated with type-I interferon levels and were associated with mortality, but not with proinflammatory response or severity. Conclusions: Distinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality according to oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.

Original language	English
Pages (from-to)	2098-2107
Number of pages	10
Journal	Journal of Allergy and Clinical Immunology
Volume	147
Issue number	6
DOIs	https://doi.org/10.1016/j.jaci.2021.03.047
State	Published - Jun 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021 American Academy of Allergy, Asthma & Immunology

Funding

This study was supported by the Fondation de France, “Tous unis contre le virus” framework Alliance (Fondation de France, AP-HP, Institut Pasteur) in collaboration with Agence Nationale de la Recherche (ANR Flash COVID19 program), by the SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University ICOViD programs, by the Programme Hospitalier de Recherche Clinique PHRC-20-0375 COVID-19 (PI: G.G.), by the Christine Kühne - Center for Allergy Research and Education (M.G., C.T.-H., and A.U.N.), and by the Initiative and Networking Fund (Immunology & Inflammation) of the Helmholtz Association (M.G., C.T.-H., and A.U.N.).

Funders	Funder number
Programme Hospitalier de Recherche Clinique	PHRC-20-0375 COVID-19
Agence Nationale de la Recherche
Institut Pasteur
Fondation de France
Helmholtz Association
Christine Kühne – Center for Allergy Research and Education
Sorbonne Université

Keywords

COVID-19
mortality
principal-component analysis
respiratory severity
serum cytokines
type-I interferons

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10.1016/j.jaci.2021.03.047

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Dorgham, K., Quentric, P., Gökkaya, M., Marot, S., Parizot, C., Sauce, D., Guihot, A., Luyt, C. E., Schmidt, M., Mayaux, J., Beurton, A., Le Guennec, L., Demeret, S., Ben Salah, E., Mathian, A., Yssel, H., Combadiere, B., Combadiere, C., Traidl-Hoffmann, C., ... Gorochov, G. (2021). Distinct cytokine profiles associated with COVID-19 severity and mortality. Journal of Allergy and Clinical Immunology, 147(6), 2098-2107. https://doi.org/10.1016/j.jaci.2021.03.047

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title = "Distinct cytokine profiles associated with COVID-19 severity and mortality",

abstract = "Background: Markedly elevated levels of proinflammatory cytokines and defective type-I interferon responses were reported in patients with coronavirus disease 2019 (COVID-19). Objective: We sought to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. Methods: Cytokine concentrations and severe acute respiratory syndrome coronavirus 2 antigen were measured at hospital admission in serum of symptomatic patients with COVID-19 (N = 115), classified at hospitalization into 3 respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS), and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal-component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N = 86). Results: At time of hospitalization, ECMO patients presented a dominant proinflammatory response with elevated levels of TNF-α, IL-6, IL-8, and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-β was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at 1 month was associated with higher levels of proinflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients, and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5\% (risk ratio, 24.3; P <.0001). Severe acute respiratory syndrome coronavirus 2 antigen levels correlated with type-I interferon levels and were associated with mortality, but not with proinflammatory response or severity. Conclusions: Distinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality according to oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.",

keywords = "COVID-19, mortality, principal-component analysis, respiratory severity, serum cytokines, type-I interferons",

author = "Karim Dorgham and Paul Quentric and Mehmet G{\"o}kkaya and St{\'e}phane Marot and Christophe Parizot and Delphine Sauce and Am{\'e}lie Guihot and Luyt, \{Charles Edouard\} and Matthieu Schmidt and Julien Mayaux and Alexandra Beurton and \{Le Guennec\}, Loic and Sophie Demeret and \{Ben Salah\}, Elyes and Alexis Mathian and Hans Yssel and B{\'e}hazine Combadiere and Christophe Combadiere and Claudia Traidl-Hoffmann and Sonia Burrel and Marcelin, \{Anne Genevi{\`e}ve\} and Zahir Amoura and Guillaume Voiriot and Neumann, \{Avidan U.\} and Guy Gorochov",

note = "Publisher Copyright: {\textcopyright} 2021 American Academy of Allergy, Asthma \& Immunology",

year = "2021",

month = jun,

doi = "10.1016/j.jaci.2021.03.047",

language = "אנגלית",

volume = "147",

pages = "2098--2107",

journal = "Journal of Allergy and Clinical Immunology",

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Dorgham, K, Quentric, P, Gökkaya, M, Marot, S, Parizot, C, Sauce, D, Guihot, A, Luyt, CE, Schmidt, M, Mayaux, J, Beurton, A, Le Guennec, L, Demeret, S, Ben Salah, E, Mathian, A, Yssel, H, Combadiere, B, Combadiere, C, Traidl-Hoffmann, C, Burrel, S, Marcelin, AG, Amoura, Z, Voiriot, G, Neumann, AU & Gorochov, G 2021, 'Distinct cytokine profiles associated with COVID-19 severity and mortality', Journal of Allergy and Clinical Immunology, vol. 147, no. 6, pp. 2098-2107. https://doi.org/10.1016/j.jaci.2021.03.047

TY - JOUR

T1 - Distinct cytokine profiles associated with COVID-19 severity and mortality

AU - Dorgham, Karim

AU - Quentric, Paul

AU - Gökkaya, Mehmet

AU - Marot, Stéphane

AU - Parizot, Christophe

AU - Sauce, Delphine

AU - Guihot, Amélie

AU - Luyt, Charles Edouard

AU - Schmidt, Matthieu

AU - Mayaux, Julien

AU - Beurton, Alexandra

AU - Le Guennec, Loic

AU - Demeret, Sophie

AU - Ben Salah, Elyes

AU - Mathian, Alexis

AU - Yssel, Hans

AU - Combadiere, Béhazine

AU - Combadiere, Christophe

AU - Traidl-Hoffmann, Claudia

AU - Burrel, Sonia

AU - Marcelin, Anne Geneviève

AU - Amoura, Zahir

AU - Voiriot, Guillaume

AU - Neumann, Avidan U.

AU - Gorochov, Guy

PY - 2021/6

Y1 - 2021/6

N2 - Background: Markedly elevated levels of proinflammatory cytokines and defective type-I interferon responses were reported in patients with coronavirus disease 2019 (COVID-19). Objective: We sought to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. Methods: Cytokine concentrations and severe acute respiratory syndrome coronavirus 2 antigen were measured at hospital admission in serum of symptomatic patients with COVID-19 (N = 115), classified at hospitalization into 3 respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS), and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal-component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N = 86). Results: At time of hospitalization, ECMO patients presented a dominant proinflammatory response with elevated levels of TNF-α, IL-6, IL-8, and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-β was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at 1 month was associated with higher levels of proinflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients, and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (risk ratio, 24.3; P <.0001). Severe acute respiratory syndrome coronavirus 2 antigen levels correlated with type-I interferon levels and were associated with mortality, but not with proinflammatory response or severity. Conclusions: Distinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality according to oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.

AB - Background: Markedly elevated levels of proinflammatory cytokines and defective type-I interferon responses were reported in patients with coronavirus disease 2019 (COVID-19). Objective: We sought to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. Methods: Cytokine concentrations and severe acute respiratory syndrome coronavirus 2 antigen were measured at hospital admission in serum of symptomatic patients with COVID-19 (N = 115), classified at hospitalization into 3 respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS), and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal-component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N = 86). Results: At time of hospitalization, ECMO patients presented a dominant proinflammatory response with elevated levels of TNF-α, IL-6, IL-8, and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-β was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at 1 month was associated with higher levels of proinflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients, and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (risk ratio, 24.3; P <.0001). Severe acute respiratory syndrome coronavirus 2 antigen levels correlated with type-I interferon levels and were associated with mortality, but not with proinflammatory response or severity. Conclusions: Distinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality according to oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.

KW - COVID-19

KW - mortality

KW - principal-component analysis

KW - respiratory severity

KW - serum cytokines

KW - type-I interferons

UR - https://www.scopus.com/pages/publications/85106943658

U2 - 10.1016/j.jaci.2021.03.047

DO - 10.1016/j.jaci.2021.03.047

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 33894209

AN - SCOPUS:85106943658

SN - 0091-6749

VL - 147

SP - 2098

EP - 2107

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 6

ER -

Distinct cytokine profiles associated with COVID-19 severity and mortality

Abstract

Bibliographical note

Funding

Keywords

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