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. 2025 Mar:187:156867.
doi: 10.1016/j.cyto.2025.156867. Epub 2025 Jan 27.

Prognostic significance of cytokine dysregulation in critically ill COVID-19 patients

Fabian Fellipe Bueno Lemos  1 , Luana Weber Lopes  1 , Gabriel Carvalho Brito  1 , Airton Idalecio Sousa Viana  1 , Caroline Tianeze de Castro  2 , Marcel Silva Luz  1 , André Pereira Gonçalves  1 , Rafael Santos Dantas Miranda Dórea  1 , Filipe Antônio França da Silva  1 , Breno Bittencourt de Brito  1 , Maria Luísa Cordeiro Santos  1 , Geovani Moreno Santos Júnior  3 , Maria Teresa Araújo de Lorenzo Barcia  3 , Renata de Amorim Marques  3 , André Bezerra Botelho  1 , Anna Carolina Saúde Dantas  1 , Fillipe Dantas Pinheiro  1 , Adriano Fernandes Teixeira  1 , Cláudio Lima Souza  1 , Márcio Vasconcelos Oliveira  1 , Dulciene Maria de Magalhães Queiroz  4 , Fabrício Freire de Melo  5
Affiliations

Prognostic significance of cytokine dysregulation in critically ill COVID-19 patients

Fabian Fellipe Bueno Lemos et al. Cytokine. 2025 Mar.

Abstract

Background: Understanding the immunopathogenesis of COVID-19 has yielded valuable insights into predicting adverse outcomes-particularly mortality. However, significant gaps persist in our comprehension of the complex interplay among the proposed pathophysiological mechanisms. Here, we aim to investigate the immunological factors associated with mortality in critically ill, unvaccinated COVID-19 patients admitted to the intensive care unit (ICU).

Methods: We conducted a single-center, prospective study involving 56 unvaccinated COVID-19 patients admitted to the ICU. Plasma cytokine levels at admission were quantified using enzyme-linked immunosorbent assay (ELISA). Continuous variables were presented as median (IQR), and categorical variables as frequencies and percentages. Non-parametric tests assessed group differences. Logistic regression and receiver operating characteristic (ROC) curve analyses identified predictors of mortality, with bootstrapping (1000 re-samplings; 95 % BCa CI) applied for model validation.

Results: Deceased patients exhibited significantly higher levels of interleukin (IL)-1β, IL-2, IL-6, transforming growth factor (TGF)-β, and interferon (IFN)-γ compared to survivors. Conversely, IL-10 and IL-27 were associated with favorable outcomes. Logistic regression modeling identified elevated IL-2 and IFN-γ levels as significant predictors of mortality. Notably, individual ROC curve analyses demonstrated that IL-1β and TGF-β had excellent discriminatory ability for mortality, while IFN-γ, IL-2, and IL-27 showed very good to excellent discriminatory capacity.

Conclusion: Our results indicate that distinct cytokine profiles differentiate survivors from non-survivors in critically ill, unvaccinated COVID-19 patients. These findings highlight the importance of cytokine dysregulation in severe COVID-19 cases and suggest potential targets for prognostic approaches. Further research is warranted to validate these results and translate them into effective clinical management strategies.

Keywords: COVID-19; Critical Illness; Cytokines; Intensive Care Unit; Prognosis; SARS-CoV-2.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fabricio Freire de Melo reports financial support was provided by Foundation for Research Support of Bahia State. Fabricio Freire de Melo reports financial support was provided by National Council for Scientific and Technological Development. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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