IL-6とCD8+ T細胞数の組み合わせはCOVID-19患者の院内死亡率の早期予測因子である

IL-6 and CD8+ T cell counts combined are an early predictor of in-hospital mortality of patients with COVID-19.

• Miao Luo
• Jing Liu
• Weiling Jiang
• Shuang Yue
• Huiguo Liu
• Shuang Wei

抄録

背景COVID-19の致死的症例は世界的に増加している。我々は、COVID-19の早期予測因子としての免疫学的パラメータの可能性をレトロスペクティブに検討した。臨床的特徴、臨床検査、免疫学的検査、放射線学的所見、転帰データを収集した。院内死亡率に関連する因子を評価するために一変量および多変量ロジスティック回帰分析を行った。結果すべてのTリンパ球サブセットのカウントは、非生存者の方が生存者よりも著しく低く、特にCD8+ T細胞のカウントが低かった。すべてのサイトカインの中でIL-6が最も有意に上昇し、10倍以上の上昇傾向を示した。多変量ロジスティック回帰分析を用いて、交絡因子を調整した後、IL-6値が20pg/mL以上、CD8+ T細胞数が165cells/μL未満の群が院内死亡率と関連していることが明らかになった。IL-6値が20pg/mL以上、CD8+T細胞数が165cells/μL未満のグループでは、高齢者と男性患者の割合が高く、併存疾患、人工呼吸、集中治療室入院、ショック、死亡の患者の割合が高かった。さらに、IL-6（>20 pg/mL）とCD8+ T細胞数（<165 cells/μL）を組み合わせたモデルの受信操作曲線は、CURB-65スコアよりも良好な弁別を示した。結論IL-6（>20 pg/mL）とCD8+ T細胞数（<165 cells/μL）は、患者を正確にリスクカテゴリーに層別化し、COVID-19死亡率を予測する2つの信頼性の高い予後指標である。

BACKGROUNDFatal cases of COVID-19 are increasing globally. We retrospectively investigated the potential of immunologic parameters as early predictors of COVID-19.METHODSA total of 1018 patients with confirmed COVID-19 were enrolled in our 2-center retrospective study. Clinical feature, laboratory test, immunological test, radiological findings, and outcomes data were collected. Univariate and multivariable logistic regression analyses were performed to evaluate factors associated with in-hospital mortality. Receiver operator characteristic (ROC) curves and survival curves were plotted to evaluate their clinical utility.RESULTSThe counts of all T lymphocyte subsets were markedly lower in nonsurvivors than in survivors, especially CD8+ T cells. Among all tested cytokines, IL-6 was elevated most significantly, with an upward trend of more than 10-fold. Using multivariate logistic regression analysis, IL-6 levels of more than 20 pg/mL and CD8+ T cell counts of less than 165 cells/μL were found to be associated with in-hospital mortality after adjusting for confounding factors. Groups with IL-6 levels of more than 20 pg/mL and CD8+ T cell counts of less than 165 cells/μL had a higher percentage of older and male patients as well as a higher proportion of patients with comorbidities, ventilation, intensive care unit admission, shock, and death. Furthermore, the receiver operating curve of the model combining IL-6 (>20 pg/mL) and CD8+ T cell counts (<165 cells/μL) displayed a more favorable discrimination than that of the CURB-65 score. The Hosmer-Lemeshow test showed a good fit of the model, with no statistical significance.CONCLUSIONIL-6 (>20 pg/mL) and CD8+ T cell counts (<165 cells/μL) are 2 reliable prognostic indicators that accurately stratify patients into risk categories and predict COVID-19 mortality.FundingThis work was supported by funding from the National Natural Science Foundation of China (no. 81772477 and 81201848).