Dataset Information

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.

SUBMITTER: Dorgham K

PROVIDER: S-EPMC8061091 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Dorgham Karim K Quentric Paul P Gökkaya Mehmet M Marot Stéphane S Parizot Christophe C Sauce Delphine D Guihot Amélie A Luyt Charles-Edouard CE Schmidt Matthieu M Mayaux Julien J Beurton Alexandra A Le Guennec Loic L Demeret Sophie S Ben Salah Elyes E Mathian Alexis A Yssel Hans H Combadiere Béhazine B Combadiere Christophe C Traidl-Hoffmann Claudia C Burrel Sonia S Marcelin Anne-Geneviève AG Amoura Zahir Z Voiriot Guillaume G Neumann Avidan U AU Gorochov Guy G

The Journal of allergy and clinical immunology 20210422 6

<h4>Background</h4>Markedly elevated levels of proinflammatory cytokines and defective type-I interferon responses were reported in patients with coronavirus disease 2019 (COVID-19).<h4>Objective</h4>We sought to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality.<h4>Methods</h4>Cytokine concentrations and severe acute respiratory syndrome coronavirus 2 antigen were measured at hospital admission in serum of symptomatic patients with COVID-19 (N = ...[more]

PMID: 33894209

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Project description:IntroductionOver the past four years, the COVID-19 pandemic has posed serious global health challenges. The severe form of disease and death resulted from the failure of immune regulatory mechanisms, closely highlighted by the dual proinflammatory cytokine and soluble immune checkpoint (sICP) storm. Identifying the individual factors impacting on disease severity, evolution and outcome, as well as any additional interconnections, have become of high scientific interest.MethodsIn this study, we evaluated a novel panel composed of ten sICPs for the predictive values of COVID-19 disease severity, mortality and Delta vs. Omicron variant infections in relation to hyperinflammatory biomarkers. The serum levels of sICPs from confirmed SARS-CoV-2 infected patients at hospital admission were determined by Luminex, and artificial neural network analysis was applied for defining the distinct patterns of molecular associations with each form of disease: mild, moderate, and severe.ResultsNotably, distinct sICP profiles characterized various stages of disease and Delta infections: while sCD40 played a central role in all defined diagrams, the differences emerged from the distribution levels of four molecules recently found and relatively less investigated (sCD30, s4-1BB, sTIM-1, sB7-H3), and their associations with various hematological and biochemical inflammatory biomarkers. The artificial neural network analysis revealed the prominent role of serum sTIM-1 and Galectin-9 levels at hospital admission in discriminating between survivors and non-survivors, as well as the role of specific anti-interleukin therapy (Tocilizumab, Anakinra) in improving survival for patients with initially high sTIM-1 levels. Furthermore, strong associations between sCD40 and Galectin-9 with suPAR defined the Omicron variant infections, while the positive match of sCD40 with sTREM-1 serum levels characterized the Delta-infected patients.ConclusionsOf importance, this study provides a comprehensive analysis of circulatory immune factors governing the COVID-19 pathology, and identifies key roles of sCD40, sTIM-1, and Galectin-9 in predicting mortality.

Dataset Information

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

Background

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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