循环肿瘤坏死因子受体与 COVID-19 患者的死亡率和疾病严重程度相关。
Circulating tumor necrosis factor receptors are associated with mortality and disease severity in COVID-19 patients.
机构信息
Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.
Department of Emergency Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
出版信息
PLoS One. 2022 Oct 11;17(10):e0275745. doi: 10.1371/journal.pone.0275745. eCollection 2022.
BACKGROUND
Although hyperinflammatory response influences the severity of coronavirus disease 2019 (COVID-19), little has been reported about the utility of tumor necrosis factor (TNF)-related biomarkers in reflecting the prognosis. We examined whether TNF receptors (TNFRs: TNFR1, TNFR2) and progranulin (PGRN) levels, in addition to interleukin 6 (IL-6) and C-reactive protein (CRP), are associated with mortality or disease severity in COVID-19 patients.
METHODS
This retrospective study was conducted at Juntendo University Hospital. Eighty hospitalized patients with various severities of COVID-19 were enrolled. Furthermore, serum levels of TNF-related biomarkers were measured using enzyme-linked immunosorbent assay.
RESULTS
Twenty-five patients died during hospitalization, and 55 were discharged. The median (25th and 75th percentiles) age of the study patients was 70 (61-76) years, 44 (55.0%) patients were males, and 26 (32.5%) patients had chronic kidney disease (CKD). When comparing with patients who received and did not receive treatment at the intensive care unit (ICU), the former had a higher tendency of being male and have diabetes, hypertension, and CKD; had higher levels of white blood cells, D-dimer, and lactate dehydrogenase; and had lower body mass index, estimated glomerular filtration rate, and lymphocyte counts. Significant differences were observed in TNFR, PGRN, IL-6, and CRP levels between each severity (mild-severe) group. Furthermore, the serum levels of TNFR, IL-6, and CRP, but not PGRN, in ICU patients were significantly higher than in the patients who were not admitted to the ICU. Multivariate logistic regression analysis demonstrated that high levels of TNFR2 were only associated with mortality in patients with COVID-19 even after adjustment for relevant clinical parameters.
CONCLUSIONS
High TNFR2 level might be helpful for predicting mortality or disease severity in patients with COVID-19.
背景
尽管过度炎症反应会影响 2019 年冠状病毒病（COVID-19）的严重程度，但关于肿瘤坏死因子（TNF）相关生物标志物在反映预后方面的作用，报道甚少。我们研究了 TNF 受体（TNFR1、TNFR2）和颗粒蛋白前体（PGRN）水平以及白细胞介素 6（IL-6）和 C 反应蛋白（CRP）除了与 COVID-19 患者的死亡率或疾病严重程度相关。
方法
本回顾性研究在顺天堂大学医院进行。共纳入 80 例不同严重程度 COVID-19 住院患者。此外，采用酶联免疫吸附试验检测 TNF 相关生物标志物的血清水平。
结果
25 例患者在住院期间死亡，55 例患者出院。研究患者的中位（25 分位和 75 分位）年龄为 70（61-76）岁，44 例（55.0%）为男性，26 例（32.5%）患有慢性肾脏病（CKD）。与入住重症监护病房（ICU）和未入住 ICU 的患者相比，前者更倾向于为男性，且患有糖尿病、高血压和 CKD；前者的白细胞、D-二聚体和乳酸脱氢酶水平更高，体重指数、估计肾小球滤过率和淋巴细胞计数更低。各组（轻症-重症）之间 TNFR、PGRN、IL-6 和 CRP 水平存在显著差异。此外，ICU 患者的 TNFR、IL-6 和 CRP 血清水平，但不是 PGRN，明显高于未入住 ICU 的患者。多变量逻辑回归分析表明，即使在调整相关临床参数后，高 TNFR2 水平仅与 COVID-19 患者的死亡率相关。
结论
高 TNFR2 水平可能有助于预测 COVID-19 患者的死亡率或疾病严重程度。
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