Amikishiyev Shirkhan, Bektaş Murat, Günver Mehmet Güven, İnce Burak, Aghamuradov Sarvan, Koca Nevzat, Şenkal Naci, Durak Görkem, Köse Murat, Erelel Mustafa, Çağatay Arif Atahan, Şimşek-Yavuz Serap, Kalayoğlu-Beşışık Sevgi, Esen Figen, Gül Ahmet
Department of Internal Medicine, Division of Rheumatology, İstanbul University İstanbul School of Medicine, İstanbul, Türkiye.
Department of Rheumatology, Biruni University School of Medicine, İstanbul, Türkiye.
Infect Dis Clin Microbiol. 2025 Jun 26;7(2):185-194. doi: 10.36519/idcm.2025.475. eCollection 2025 Jun.
OBJECTIVE: During the COVID-19 pandemic, a subset of patients developed COVID-19-associated hyperinflammation (HIC), which resulted in increased mortality. While early and effective anti-inflammatory therapies, such as glucocorticoids and tocilizumab, improved survival, tools to predict treatment response remained lacking. This study aimed to identify predictors of clinical outcomes in patients who received tocilizumab for HIC. MATERIALS AND METHODS: We retrospectively analyzed the records of hospitalized adult patients with COVID-19 treated between March and December 2020. Patients who received tocilizumab for HIC constituted the study cohort. Dynamic changes in the laboratory parameters were analyzed, and the HIC scores (≥35) were calculated to assess disease severity and treatment response. RESULTS: Out of 961 hospitalized COVID-19 patients, 150 who received tocilizumab were identified. Among them, 124 were treated with only tocilizumab in the first phase of the pandemic (from March to September 2020). After this period, 26 patients also received glucocorticoids, typically initiated 2-3 days prior to tocilizumab administration. Anakinra treatment was given to 22 patients whose inflammatory parameters did not resolve with tocilizumab. Findings of HIC were treated in 122 patients (84%), with a significant reduction in C-reactive protein (CRP) levels (from 121.8 ± 8.2 to 9.8 ± 2.8 mg/L). Despite tocilizumab treatment, no effective resolution of the CRP response was observed (from 172 ± 22.8 to 53 ± 8 mg/L by Day 5) among non-survivors, alongside increasing trends in neutrophil count, D-dimer, lactate dehydrogenase (LDH), troponin, and creatine kinase. The composite HIC scores progressively decreased in survivors until the last day of hospitalization but increased in non-survivors (33.8 ± 0.14 vs. 72.3 ± 0.13). CONCLUSION: Analysis of this cohort indicated that neutrophil count, CRP, D-dimer, LDH, troponin, and creatine kinase levels may serve as predictors of tocilizumab efficacy on Day 5. The score developed to diagnose HIC can also be used for monitoring treatment response.
目的：在新冠疫情期间，一部分患者出现了与新冠病毒相关的过度炎症反应（HIC），这导致死亡率上升。虽然早期有效的抗炎治疗，如糖皮质激素和托珠单抗，提高了生存率，但仍缺乏预测治疗反应的工具。本研究旨在确定接受托珠单抗治疗HIC患者的临床结局预测因素。 材料与方法：我们回顾性分析了2020年3月至12月期间住院的成年新冠患者的记录。接受托珠单抗治疗HIC的患者构成研究队列。分析实验室参数的动态变化，并计算HIC评分（≥35）以评估疾病严重程度和治疗反应。 结果：在961例住院的新冠患者中，确定了150例接受托珠单抗治疗的患者。其中，124例在疫情第一阶段（2020年3月至9月）仅接受托珠单抗治疗。在此之后，26例患者还接受了糖皮质激素治疗，通常在托珠单抗给药前2 - 3天开始使用。22例炎症参数未因托珠单抗而缓解的患者接受了阿那白滞素治疗。122例患者（84%）出现HIC表现，C反应蛋白（CRP）水平显著降低（从121.8±8.2降至9.8±2.8mg/L）。在非幸存者中，尽管接受了托珠单抗治疗，但未观察到CRP反应有效缓解（到第5天从172±22.8降至5±8mg/L），同时中性粒细胞计数、D - 二聚体、乳酸脱氢酶（LDH）、肌钙蛋白和肌酸激酶呈上升趋势。幸存者的综合HIC评分在住院最后一天前逐渐下降，但非幸存者则上升（33.8±0.14对72.3±0.13）。 结论：该队列分析表明，中性粒细胞计数、CRP、D - 二聚体、LDH、肌钙蛋白和肌酸激酶水平可能作为第5天托珠单抗疗效的预测指标。用于诊断HIC的评分也可用于监测治疗反应。
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