Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil.
Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil.
Front Immunol. 2023 Aug 16;14:1229611. doi: 10.3389/fimmu.2023.1229611. eCollection 2023.
The novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological processes arising from viral damage or aggressive immunological response. We hypothesized that high daily dose methylprednisolone improved the injury biomarkers and serum cytokine profiles in COVID-19 patients.
Injury biomarker and cytokine analysis was performed on 50 SARS-Cov-2 negative controls and 101 hospitalized severe COVID-19 patients: 49 methylprednisolone-treated (MP group) and 52 placebo-treated serum samples. Samples from the treated groups collected on days D1 (pre-treatment) all the groups, D7 (2 days after ending therapy) and D14 were analyzed. Luminex assay quantified the biomarkers HMGB1, FABP3, myoglobin, troponin I and NTproBNP. Immune mediators (CXCL8, CCL2, CXCL9, CXCL10, TNF, IFN-γ, IL-17A, IL-12p70, IL-10, IL-6, IL-4, IL-2, and IL-1β) were quantified using cytometric bead array.
At pretreatment, the two treatment groups were comparable demographically. At pre-treatment (D1), injury biomarkers (HMGB1, TnI, myoglobin and FABP3) were distinctly elevated. At D7, HMGB1 was significantly higher in the MP group (p=0.0448) compared to the placebo group, while HMGB1 in the placebo group diminished significantly by D14 (p=0.0115). Compared to healthy control samples, several immune mediators (IL-17A, IL-6, IL-10, MIG, MCP-1, and IP-10) were considerably elevated at baseline (all p≤0.05). At D7, MIG and IP-10 of the MP-group were significantly lower than in the placebo-group (p=0.0431, p=0.0069, respectively). Longitudinally, IL-2 (MP-group) and IL-17A (placebo-group) had increased significantly by D14. In placebo group, IL-2 and IL-17A continuously increased, as IL-12p70, IL-10 and IP-10 steadily decreased during follow-up. The MP treated group had IL-2, IFN-γ, IL-17A and IL-12p70 progressively increase while IL-1β and IL-10 gradually decreased towards D14. Moderate to strong positive correlations between chemokines and cytokines were observed on D7 and D14.
These findings suggest MP treatment could ameliorate levels of myoglobin and FABP3, but appeared to have no impact on HMGB1, TnI and NTproBNP. In addition, methylprednisolone relieves the COVID-19 induced inflammatory response by diminishing MIG and IP-10 levels. Overall, corticosteroid (methylprednisolone) use in COVID-19 management influences the immunological molecule and injury biomarker profile in COVID-19 patients.
新型冠状病毒病 2019（COVID-19）在各种器官系统中表现出复杂的病理生理效应。在 COVID-19 之后，与病毒损伤或强烈的免疫反应引起的生理过程改变相关的生物标志物和细胞因子平衡发生了变化。我们假设大剂量甲基强的松龙可改善 COVID-19 患者的损伤生物标志物和血清细胞因子谱。
对 50 名 SARS-CoV-2 阴性对照和 101 名住院重症 COVID-19 患者进行损伤生物标志物和细胞因子分析：49 名甲基强的松龙治疗（MP 组）和 52 名安慰剂治疗血清样本。对治疗组的样本在 D1（治疗前）、D7（治疗结束后第 2 天）和 D14 进行分析。Luminex 分析定量测定 HMGB1、FABP3、肌红蛋白、肌钙蛋白 I 和 NTproBNP 等生物标志物。使用流式细胞术检测细胞因子（CXCL8、CCL2、CXCL9、CXCL10、TNF、IFN-γ、IL-17A、IL-12p70、IL-10、IL-6、IL-4、IL-2 和 IL-1β）。
在治疗前，两组患者在人口统计学上无差异。在治疗前（D1），损伤生物标志物（HMGB1、TnI、肌红蛋白和 FABP3）明显升高。在 D7 时，与安慰剂组相比，MP 组的 HMGB1 明显升高（p=0.0448），而安慰剂组的 HMGB1 在 D14 时明显降低（p=0.0115）。与健康对照样本相比，一些免疫介质（IL-17A、IL-6、IL-10、MIG、MCP-1 和 IP-10）在基线时明显升高（均 p≤0.05）。在 D7 时，MP 组的 MIG 和 IP-10 明显低于安慰剂组（p=0.0431，p=0.0069）。纵向观察发现，IL-2（MP 组）和 IL-17A（安慰剂组）在 D14 时显著升高。在安慰剂组中，IL-2 和 IL-17A 在随访期间持续升高，而 IL-12p70、IL-10 和 IP-10 则持续下降。在接受 MP 治疗的组中，IL-2、IFN-γ、IL-17A 和 IL-12p70 逐渐增加，而 IL-1β和 IL-10 则逐渐减少，直至 D14。在 D7 和 D14 时观察到趋化因子和细胞因子之间存在中度至强正相关。
这些发现表明，MP 治疗可改善肌红蛋白和 FABP3 的水平，但对 HMGB1、TnI 和 NTproBNP 似乎没有影响。此外，甲基强的松龙通过降低 MIG 和 IP-10 水平来缓解 COVID-19 诱导的炎症反应。总体而言，COVID-19 管理中皮质类固醇（甲基强的松龙）的使用会影响 COVID-19 患者的免疫分子和损伤生物标志物谱。
