Schmidt Wiktor, Pawlak-Buś Katarzyna, Jóźwiak Barbara, Leszczyński Piotr
Department of Rheumatology, Systemic Connective Tissue Diseases and Immunotherapy of Rheumatic Diseases, J. Strus Municipal Hospital, 61-285 Poznan, Poland.
Department of Internal Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland.
J Clin Med. 2023 Mar 22;12(6):2429. doi: 10.3390/jcm12062429.
Hyperinflammation in COVID-19 plays a crucial role in pathogenesis and severity; thus, many immunomodulatory agents are applied in its treatment. We aimed to identify good clinical response predictors of tocilizumab (TCZ) treatment in severe COVID-19, among clinical, laboratory, and radiological variables. We conducted a prospective, observational study with 120 patients with severe COVID-19 not improving despite dexamethasone (DEX) treatment. We used parametric and non-parametric statistics, univariate logistic regression, receiver operating characteristic (ROC) curves, and nonlinear factors tertile analysis. In total, 86 (71.7%) patients achieved the primary outcome of a good clinical response to TCZ. We identified forty-nine predictive factors with potential utility in patient selection and treatment monitoring. The strongest included time from symptom onset between 9 and 12 days, less than 70% of estimated radiological lung involvement, and lower activity of lactate dehydrogenase. Additional predictors were associated with respiratory function, vitamin D concentration, comorbidities, and inflammatory/organ damage biomarkers. Adverse events analysis proved the safety of such a regimen. Our study confirmed that using TCZ early in the hyperinflammatory phase, before severe respiratory failure development, is most beneficial. Considering the described predictive factors, employing simple and widely available laboratory, radiological, and clinical tools can optimize patient selection for immunomodulatory treatment with TCZ.
新型冠状病毒肺炎（COVID-19）中的过度炎症反应在发病机制和疾病严重程度中起关键作用；因此，许多免疫调节药物被应用于其治疗。我们旨在在临床、实验室和影像学变量中，确定托珠单抗（TCZ）治疗重症COVID-19的良好临床反应预测指标。我们对120例尽管接受了地塞米松（DEX）治疗但病情仍无改善的重症COVID-19患者进行了一项前瞻性观察性研究。我们使用了参数和非参数统计、单因素逻辑回归、受试者工作特征（ROC）曲线和非线性因素三分位数分析。总共86例（71.7%）患者达到了对TCZ良好临床反应的主要结局。我们确定了49个在患者选择和治疗监测中具有潜在效用的预测因素。最有力的因素包括症状出现后9至12天、估计肺部影像学受累小于70%以及乳酸脱氢酶活性较低。其他预测因素与呼吸功能、维生素D浓度、合并症以及炎症/器官损伤生物标志物有关。不良事件分析证明了该治疗方案的安全性。我们的研究证实，在过度炎症阶段早期、严重呼吸衰竭发生之前使用TCZ最为有益。考虑到所描述的预测因素，使用简单且广泛可用的实验室、影像学和临床工具可以优化TCZ免疫调节治疗的患者选择。
