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

Department of Dermatology and Allergology

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

57 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

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

@article{04ef368441554f8cb0728b8b3b30d540,

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 = "English",

volume = "147",

pages = "2098--2107",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

number = "6",

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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 - http://www.scopus.com/inward/record.url?scp=85106943658&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2021.03.047

DO - 10.1016/j.jaci.2021.03.047

M3 - 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

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