Department of Pulmonary Medicine, Miguel Servet University Hospital, CIBERES, Instituto de Investigación Sanitaria (ISS) Aragón, Avenida Isabel La Católica 1-9, 50009, Zaragoza, Spain.
Department of Biochemistry, San Jorge Hospital, Huesca, Spain.
Respir Res. 2023 May 5;24(1):125. doi: 10.1186/s12931-023-02426-1.
Severe COVID-19 entails a dysregulated immune response, most likely inflammation related to a lack of virus control. A better understanding of immune toxicity, immunosuppression balance, and COVID-19 assessments could help determine whether different clinical presentations are driven by specific types of immune responses. The progression of the immune response and tissular damage could predict outcomes and may help in the management of patients.
We collected 201 serum samples from 93 hospitalised patients classified as moderately, severely, and critically ill. We differentiated the viral, early inflammatory, and late inflammatory phases and included 72 patients with 180 samples in separate stages for longitudinal study and 55 controls. We studied selected cytokines, P-selectin, and the tissue damage markers lactate dehydrogenase (LDH) and cell-free DNA (cfDNA).
TNF-α, IL-6, IL-8, and G-CSF were associated with severity and mortality, but only IL-6 increased since admission in the critical patients and non-survivors, correlating with damage markers. The lack of a significant decrease in IL-6 levels in the critical patients and non-survivors in the early inflammatory phase (a decreased presence in the other patients) suggests that these patients did not achieve viral control on days 10-16. For all patients, lactate dehydrogenase and cfDNA levels increased with severity, and cfDNA levels increased in the non-survivors from the first sample (p = 0.002) to the late inflammatory phase (p = 0.031). In the multivariate study, cfDNA was an independent risk factor for mortality and ICU admission.
The distinct progression of IL-6 levels in the course of the disease, especially on days 10-16, was a good marker of progression to critical status and mortality and could guide the start of IL-6 blockade. cfDNA was an accurate marker of severity and mortality from admission and throughout COVID-19 progression.
严重的 COVID-19 涉及免疫反应失调，很可能与缺乏病毒控制有关的炎症。更好地了解免疫毒性、免疫抑制平衡以及 COVID-19 的评估可以帮助确定不同的临床表现是否由特定类型的免疫反应驱动。免疫反应和组织损伤的进展可以预测结果，并可能有助于患者的管理。
我们从 93 名住院患者中收集了 201 份血清样本，这些患者分为中度、重度和危重症。我们区分了病毒、早期炎症和晚期炎症阶段，并对 72 名患者的 180 份样本进行了单独的阶段进行了纵向研究，包括 55 名对照。我们研究了选定的细胞因子、P 选择素以及组织损伤标志物乳酸脱氢酶 (LDH) 和无细胞 DNA (cfDNA)。
TNF-α、IL-6、IL-8 和 G-CSF 与严重程度和死亡率相关，但只有 IL-6 在危重症患者和非幸存者中自入院以来增加，与损伤标志物相关。在早期炎症阶段，危重症患者和非幸存者中 IL-6 水平没有明显下降（其他患者中下降），这表明这些患者在第 10-16 天没有控制病毒。对于所有患者，乳酸脱氢酶和 cfDNA 水平随着严重程度的增加而增加，cfDNA 水平在非幸存者中从第一个样本开始增加（p=0.002）到晚期炎症阶段（p=0.031）。在多变量研究中，cfDNA 是死亡率和 ICU 入院的独立危险因素。
疾病过程中 IL-6 水平的不同进展，尤其是第 10-16 天，是向危重症状态和死亡率进展的良好标志物，并可能指导 IL-6 阻断的开始。cfDNA 是入院和 COVID-19 进展期间严重程度和死亡率的准确标志物。
