Abstract
The main aim of this study was to identify the most relevant cytokines which, when assessed in the earliest stages from hospital admission, may help to select COVID-19 patients with worse prognosis. A retrospective observational study was conducted in 415 COVID-19 patients (272 males; mean age 68 ± 14 years) hospitalized between May 2020 and March 2021. Within the first 72 h from hospital admission, patients were tested for a large panel of biomarkers, including C-reactive protein (CRP), Mid-regional proadrenomedullin (MR-proADM), Interferon-γ, interleukin 6 (IL-6), IL-1β, IL-8, IL-10, soluble IL2-receptor-α (sIL2Rα), IP10 and TNFα. Extensive statistical analyses were performed (correlations, t -tests, ranking tests and tree modeling). The mortality rate was 65/415 (15.7%) and a negative outcome (death and/or orotracheal intubation) affected 98/415 (23.6%) of cases. Univariate tests showed the majority of biomarkers increased in severe patients, but ranking tests helped to select the best variables to put on decisional tree modeling which identified IL-6 as the first dichotomic marker with a cut-off of 114 pg/mL. Then, a good synergy was found between IL-10, MR-proADM, sIL2Rα, IP10 and CRP in increasing the predictive value in classifying patients at risk or not for a negative outcome. In conclusion, beside IL-6, a panel of other cytokines representing the degree of immunoparalysis and the anti-inflammatory response (IP10, sIL2Rα and IL-10) showed synergic role when combined to biomarkers of systemic inflammation and endothelial dysfunction (CRP, MR-proADM) and may also better explain disease pathogenesis and suggests targeted intervention.
Keywords: COVID-19; IL-10; IL-6; IP10; cytokine; proadrenomedullin; prognosis; sIL2Rα.
【저자키워드】 COVID-19, Prognosis, IL-6, cytokine, IL-10, IP10, proadrenomedullin, sIL2Rα., 【초록키워드】 Biomarker, Biomarkers, Cytokines, Hospitalized, Prognosis, IL-6, interferon, intubation, C-reactive protein, risk, CRP, Intervention, outcome, observational study, Endothelial dysfunction, Predictive value, interleukin 6, interleukin, Patient, death, IL-8, age, Hospital admission, systemic inflammation, mortality rate, IL-10, synergy, immunoparalysis, COVID-19 patients, MR-proADM, marker, IP10, IL-1β, retrospective, statistical analysis, COVID-19 patient, best, Predictive, disease pathogenesis, interferon-γ, orotracheal intubation, severe patients, help, worse prognosis, Stage, TNFα, correlations, cut-off, anti-inflammatory response, variable, tested, identify, performed, affected, conducted, majority, representing, explain, Extensive, 【제목키워드】 negative, Bench, Definite, Panel,