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


Creative Commons License

Amikishiyev S., Deniz R., GÜNVER M. G., Aghamuradov S., Koca N., Ince B., ...Daha Fazla

Frontiers in Immunology, cilt.17, 2026 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 17
  • Basım Tarihi: 2026
  • Doi Numarası: 10.3389/fimmu.2026.1722572
  • Dergi Adı: Frontiers in Immunology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Directory of Open Access Journals, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Health Research Premium Collection (ProQuest)
  • Anahtar Kelimeler: anakinra, COVID-19, hemophagocytic lymphohistiocytosis, HIC score, hyperinflammation, macrophage activation syndrome, prognosis, treatment response prediction
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • İstanbul Üniversitesi Adresli: Evet

Özet

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.