Dynamic hyperinflammatory response assessment using HIC scores in COVID-19: application to a large series of patients receiving anakinra.

Introduction: Hyperinflammatory responses substantially contribute to morbidity and mortality in severe COVID-19 and share features with secondary hemophagocytic lymphohistiocytosis and macrophage activation syndrome. The Hyperinflammation in COVID-19 (HIC) criteria allow early diagnosis and may provide a framework for dynamic treatment monitoring. Methods: We retrospectively analyzed 218 hospitalized patients with hyperinflammation (HIC ≥35) who received anakinra at a tertiary referral center. The daily anakinra dose (100-800 mg/day, administered intravenously or subcutaneously) was adjusted according to clinical and laboratory parameters. The primary outcome was in-hospital mortality. Secondary outcomes included time to ≥50% CRP reduction, ICU admission, mechanical ventilation, and dynamic changes in ΔHIC and inflammatory biomarkers. Results: Overall mortality was 12.8%. Survivors achieved earlier CRP reduction than non-survivors (3.1 vs. 4.7 days) and showed a progressive decline in HIC, whereas non-survivors had persistently elevated or rising scores. Divergence in ΔHIC and other parameters, including neutrophil count, D-dimer, LDH, procalcitonin, and creatine kinase, emerged within 3-4 days. ROC analysis demonstrated that HIC on the day of anakinra initiation and at the final assessment discriminated survivors from non-survivors (AUC 0.75, p < 0.001; cut-offs 70.8 and 66.5, with high sensitivity but moderate specificity), whereas baseline and first-response-day HIC had limited predictive value (AUC approximately 0.50-0.55) . Discussion: These findings support the HIC score as both a diagnostic and dynamic monitoring tool during IL-1 blockade. Initiating anakinra when HIC is ≥35 but <70, and reassessing treatment response after 3-4 days using ΔHIC together with CRP kinetics, may help optimize outcomes.