INVESTIGATING CYTOKINE STORM MARKERS IN SEVERE COVID-19-RELATED ARDS CASES

Abstract

In a prospective observational cohort of 100 mechanically ventilated adults with RT-PCR–confirmed SARS-CoV-2 infection, peripheral blood was sampled on days 0, 3, and 7 following intubation to quantify eight key cytokines (IL-6, IL-1β, TNF-α, IL-8/CXCL8, IP-10/CXCL10, IL-18, GM-CSF, M-CSF) via multiplex bead–based immunoassay. Mixed‐effects linear regression revealed that IL-18 and IP-10 concentrations were highest at enrollment (median 120 pg/mL and 100 pg/mL, respectively), peaked on day 3 (180 pg/mL and 150 pg/mL), and declined by day 7 (140 pg/mL and 110 pg/mL), and that elevated IP-10 and IL-6 levels exhibited the strongest inverse correlations with ventilator‐free days (r = –0.65 and r = –0.60; p < 0.001 for both). Receiver operating characteristic analysis demonstrated that IP-10 (AUC 0.88; 95% CI 0.84–0.92; sensitivity 82%; specificity 85%) and IL-6 (AUC 0.85; 95% CI 0.80–0.90; sensitivity 80%; specificity 75%) were the most accurate predictors of 28-day mortality. Semi-structured interviews with 20 treating clinicians underscored “patient heterogeneity” and “timing of sampling” as primary barriers to routine cytokine monitoring. These data therefore delineate a reproducible cytokine signature—particularly IP-10, IL-6, and IL-18—that correlates with disease severity and mortality in severe COVID-19–related ARDS, suggesting that their integration into adaptive immunomodulatory protocols, with careful attention to sampling timing and patient stratification, may enhance therapeutic targeting and improve clinical outcomes.