Serum cytokine profiling reveals CXCL10 (IP-10) as a major predictor of severe COVID-19 outcomes in hospitalized patients during the first pandemic wave in Italy

IntroductionCoronavirus disease 2019 (COVID-19) severity is closely associated with dysregulated inflammatory responses, with cytokines and chemokines emerging as key mediators and potential early biomarkers of adverse clinical outcomes. A retrospective study on 103 RT-PCR-confirmed COVID-19 patients during the first pandemic wave (January-May 2020) was performed to evaluate the prognostic value of a panel of cytokines and chemokines measured at hospital admission.MethodsSamples and clinical data were collected at the Department of Public Health and Infectious Diseases, Sapienza University of Rome, and sent to Istituto Superiore di Sanità for further characterization.

Serum concentrations of IL-1β, IL-6, IL-8, IL-10, TNF-α, CCL3, and CXCL10 (IP-10) were quantified using multiplex ELISA. Associations with in-hospital mortality, intensive care unit (ICU) admission, and a composite outcome (death or ICU admission) were assessed using multivariable logistic regression.ResultsICU admission occurred in 6.8% of patients and mortality in 11.7%.

Among inflammatory mediators, CXCL10 emerged as the strongest predictor of adverse outcomes. In adjusted models, each 1,000 pg/mL increase in CXCL10 was associated with increased odds of death (OR 1.26; 95% CI 1.17-1.35), ICU admission (OR 1.13; 95% CI 1.06-1.21), and the composite outcome (OR 1.21; 95% CI 1.12-1.31).

Elevated respiratory frequency and blood urea nitrogen were also independently associated with worse outcomes, while TNF-α tended to be associated with ICU admission. Conversely, IL-6 and other cytokines were not significant predictors in the multivariable models.

DiscussionThese findings identify CXCL10 as a key early immunological predictor of COVID-19 severity, suggesting that its integration with clinical parameters may improve risk stratification and guide targeted management. CXCL10 may also represent a potential therapeutic target, warranting validation in larger prospective studies.