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Omicron BA.5.2变异株感染住院患者临床特征及炎症指标对疾病预后的预测作用

刘欢 黄晓玲 代梦莹 郭杰洁 高峰

刘欢, 黄晓玲, 代梦莹, 郭杰洁, 高峰. Omicron BA.5.2变异株感染住院患者临床特征及炎症指标对疾病预后的预测作用[J]. 协和医学杂志, 2023, 14(5): 1038-1045. doi: 10.12290/xhyxzz.2023-0055
引用本文: 刘欢, 黄晓玲, 代梦莹, 郭杰洁, 高峰. Omicron BA.5.2变异株感染住院患者临床特征及炎症指标对疾病预后的预测作用[J]. 协和医学杂志, 2023, 14(5): 1038-1045. doi: 10.12290/xhyxzz.2023-0055
LIU Huan, HUANG Xiaoling, DAI Mengying, GUO Jiejie, GAO feng. Clinical Characteristics and Inflammatory Markers of Omicron BA.5.2 Variant Infection in Hospitalized Patients and Their Predictive Role in Disease Prognosis[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(5): 1038-1045. doi: 10.12290/xhyxzz.2023-0055
Citation: LIU Huan, HUANG Xiaoling, DAI Mengying, GUO Jiejie, GAO feng. Clinical Characteristics and Inflammatory Markers of Omicron BA.5.2 Variant Infection in Hospitalized Patients and Their Predictive Role in Disease Prognosis[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(5): 1038-1045. doi: 10.12290/xhyxzz.2023-0055

Omicron BA.5.2变异株感染住院患者临床特征及炎症指标对疾病预后的预测作用

doi: 10.12290/xhyxzz.2023-0055
详细信息
    通讯作者:

    高峰, E-mail: xjgf@sina.com

  • 中图分类号: R511; R446

Clinical Characteristics and Inflammatory Markers of Omicron BA.5.2 Variant Infection in Hospitalized Patients and Their Predictive Role in Disease Prognosis

More Information
  • 摘要:   目的  分析Omicron BA.5.2变异株感染住院患者临床特征及炎症指标,筛选可能的预后诊断标志物。  方法  回顾性收集2022年8月1日—11月30日新疆维吾尔自治区人民医院收治的Omicron BA.5.2变异株感染住院患者临床资料,根据疾病严重程度将患者分为轻型、普通型、重型和危重型,比较4组临床资料差异,采用二元Logistic回归法分析与疾病严重程度相关的炎症指标,采用多因素Logistic回归法分析各指标与疾病预后的相关性,采用受试者工作特征(receiver operator characteristic, ROC)曲线分析各指标对疾病严重程度和预后的诊断价值。  结果  共纳入符合纳入和排除标准的3006例患者,其中男性1522例(50.63%)、女性1484例(49.37%);平均年龄为(58.72±18.01)(14~96)岁;根据疾病严重程度分为轻型(40.98%,1232/3006)、普通型(52.56%,1580/3006)、重型(4.26%,128/3006)、危重型(2.20%,66/3006);各组在合并基础疾病(心脏病、糖尿病、高血压、肾脏病、肺部疾病、恶性肿瘤、脑部疾病、病毒性肝炎和自身免疫性疾病)方面均具有显著性差异(P均<0.01);住院期间共死亡74例(2.43%),其中危重型46例(63.01%)、重型19例(26.03%)、普通型7例(9.60%)、轻型2例(2.74%),年龄≥70岁的死亡患者占比为75.68%(56/74),所有死亡患者均为合并基础疾病人群;C-反应蛋白(C-reactive protein,CRP)、白蛋白是疾病严重程度的独立危险因素,且CRP与疾病严重程度呈显著正相关(P=0.002),白蛋白水平与疾病严重程度呈显著负相关(P<0.001);CRP、全身炎症反应指数(systemic inflammatory response index,SIRI)、全身免疫炎症指数(systemic immune-inflammation index,SII)为疾病预后的独立危险因素,且CRP(P=0.027)、SIRI(P=0.025)与疾病预后呈显著正相关,SII与疾病预后呈显著负相关(P=0.021);CRP、白细胞介素-6(interleukin-6,IL-6)、D-二聚体、中性粒细胞与淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)对应的曲线下面积(area under the curve,AUC)均>0.70,对疾病严重程度分型的诊断价值较高;CRP、IL-6、降钙素原(procalcitonin, PCT)、D-二聚体、肌钙蛋白T(troponin T,TnT)、肌钙蛋白Ⅰ(troponin Ⅰ, TnⅠ)、NLR、SII、血小板与淋巴细胞比值(platelet to lymphocyte ratio,PLR)、单核细胞与淋巴细胞比值(monocyte to lymphocyte ratio,MLR)对应的AUC均>0.70,对死亡或存活的预后诊断价值较高。  结论  不同疾病严重程度的Omicron BA.5.2变异株感染住院患者临床特征比较具有显著差异,结合CRP、IL-6、PCT、D-二聚体、TnT、TnⅠ、NLR、SII、PLR、MLR的预测模型可早期识别Omicron BA.5.2变异株感染住院患者中的高危人群,及时进行早期诊断和治疗。
    作者贡献:刘欢负责论文设计、数据统计及论文撰写;代梦莹负责收集、整理临床资料及患者随访;郭杰洁负责数据整理、统计、分析;黄晓玲、高峰负责论文设计、实施及修订。
    利益冲突:所有作者均声明不存在利益冲突
  • 图  1  炎症指标预测Omicron BA.5.2感染住院患者疾病严重程度的受试者工作特征曲线

    CRP、ESR、IL-6、PCT、TnT、Tn Ⅰ、dNLR、NLR、SII、SIRI、PLR、MLR:同表 1

    图  2  炎症指标预测Omicron BA.5.2感染住院患者疾病预后的受试者工作特征曲线

    CRP、ESR、IL-6、PCT、dNLR、NLR、SII、SIRI、PLR、MLR:同表 1

    表  1  3006例Omicron BA.5.2感染住院患者一般资料比较

    轻型(n=1232) 普通型(n=1580) 重型(n=128) 危重型(n=66) F/H P
    年龄(x±s, 岁) 52.76±17.45 61.60±17.11 72.27±14.76 74.70±14.23 110.939 <0.001
    住院天数(x±s, d) 8.83±7.34 12.44±7.81 13.68±8.75 14.07±7.84 11.486 <0.001
    入院前症状出现时间[M(P25, P75), d] 2.0(2.0, 3.0) 2.0(2.0, 3.0) 2.0(2.0, 3.0) 2.0(2.0, 3.0) 0.507 0.917
    BMI(x±s, kg/m2) 23.86±3.40 24.14±3.16 23.86±2.28 24.08±2.27 1.819 0.141
    入院氧分压(x±s, mm Hg) 86.93±21.66 87.20±23.49 82.72±28.48 85.66±31.93 1.531 0.204
    血氧饱和度(x±s, %) 95.82±2.48 95.69±2.79 93.78±5.58 95.08±3.76 20.494 <0.001
    CRP[M(P25, P75), mg/L] 6.240(2.2, 18.8) 7.875(2.4, 24.5) 53.720(15.5, 100.8) 75.475(23.0, 171.2) 208.752 <0.001
    ESR(x±s, mm/h) 16.59±7.60 17.19±9.18 27.46±20.08 25.64±16.42 66.832 <0.001
    IL-6[M(P25, P75), ng/L] 9.650(4.7, 25.5) 10.475(5.0, 28.4) 38.430(13.2, 104.3) 76.080(30.3, 275.5) 156.806 <0.001
    PCT[M(P25, P75), μg/L] 0.080(0.0, 0.2) 0.090(0.1, 0.2) 0.240(0.1, 0.9) 0.530(0.2, 2.7) 110.902 <0.001
    白蛋白(x±s, g/L) 33.72±14.35 34.72±12.40 31.61±8.17 32.03±8.46 3.659 0.012
    球蛋白(x±s, g/L) 28.04±3.95 28.62±3.82 29.96±4.91 28.88±4.45 11.904 <0.001
    D-二聚体[M(P25, P75), mg/L] 0.339(0.1, 0.8) 0.299(0.1, 0.8) 0.893(0.4, 2.2) 1.159(0.6, 5.8) 137.481 <0.001
    肌酐[M(P25, P75), μmol/L] 69.26(55.41, 96.45) 69.94(55.69,96.26) 81.4(55.45, 173.05) 69.90(55.30,91.90) 3.533 0.316
    肌酸激酶[M(P25, P75), U/L] 69.000(44.0, 117.0) 70.000(44.0, 126.0) 76.000(45.5, 142.5) 106.000(64.8, 413.0) 22.08 <0.001
    TnT[M(P25, P75), μg/L] 0.015(0.0, 0.0) 0.014(0.0, 0.0) 0.033(0.0, 0.1) 0.065(0.0, 0.2) 82.581 <0.001
    TnⅠ[M(P25, P75), μg/L] 0.019(0.0, 0.1) 0.011(0.0, 0.0) 0.035(0.0, 0.2) 0.080(0.0, 0.5) 89.339 <0.001
    白细胞计数(x±s, 109/L) 5.66±2.54 6.32±2.76 8.09±4.38 10.34±4.97 82.378 <0.001
    淋巴细胞计数(x±s, 109/L) 1.38±0.67 1.32±0.68 0.80±0.50 0.81±0.66 41.036 <0.001
    单核细胞计数(x±s, 109/L) 0.45±0.18 0.47±0.20 0.47±0.24 0.42±0.21 5.047 0.002
    中性粒细胞计数(x±s, 109/L) 3.64±2.08 4.20±2.22 4.85±2.86 5.60±2.90 32.765 <0.001
    血小板计数(x±s, 109/L) 202.03±73.81 197.47±73.60 160.45±68.13 155.97±68.45 19.426 <0.001
    dNLR[M(P25, P75)] 1.670(1.1, 2.6) 2.090(1.3, 3.3) 3.460(0.8, 5.4) 2.090(0.5, 4.5) 58.486 <0.001
    NLR(x±s) 3.48±3.25 4.24±3.77 7.17±5.55 7.12±3.62 57.516 <0.001
    SII(x±s) 686.23±676.52 826.52±773.60 1088.07±966.25 1273.54±919.02 25.095 <0.001
    SIRI[M(P25, P75)] 1.010(0.5, 2.0) 1.340(0.7, 2.8) 2.555(1.3, 4.7) 2.640(1.9, 5.6) 151.871 <0.001
    PLR(x±s) 174.67±97.85 180.33±105.17 234.66±136.72 239.75±123.91 19.793 <0.001
    MLR(x±s) 0.42±0.30 0.45±0.30 0.63±0.38 0.65±0.33 31.351 <0.001
    BMI:体质量指数;CRP:C-反应蛋白;ESR:红细胞沉降率;IL-6:白细胞介素-6;PCT:降钙素原;TnT:肌钙蛋白T;Tn Ⅰ:肌钙蛋白Ⅰ;NLR:中性粒细胞与淋巴细胞比值;dNLR:动态NLR;SII:全身免疫炎症指数;SIRI:全身炎症反应指数;PLR:血小板与淋巴细胞比值;MLR:单核细胞与淋巴细胞比值
    下载: 导出CSV

    表  2  3006例Omicron BA.5.2住院患者疾病严重程度影响因素分析

    指标 回归系数 标准误 Z χ2 P OR 95% CI
    年龄(岁) 0.020 0.015 1.288 1.659 0.198 1.020 0.990~1.051
    住院天数(d) 0.988 0.788 1.254 1.573 0.210 2.686 0.573~12.579
    血氧饱和度(%) -0.020 0.034 -0.580 0.337 0.562 0.981 0.918~1.048
    CRP(mg/L) 0.015 0.005 3.133 9.819 0.002 1.015 1.006~1.025
    ESR(mm/h) -0.012 0.010 -1.158 1.342 0.247 0.989 0.969~1.008
    IL-6(ng/L) 0.000 0.001 0.851 0.723 0.395 1.000 0.999~1.002
    PCT(μg/L) 0.094 0.110 0.859 0.738 0.390 1.099 0.886~1.362
    白蛋白(g/L) -0.191 0.042 -4.578 20.954 <0.001 0.826 0.761~0.896
    球蛋白(g/L) 0.076 0.043 1.779 3.163 0.075 1.079 0.992~1.173
    D-二聚体(mg/L) -0.000 0.039 -0.007 0.000 0.995 1.000 0.926~1.080
    肌酸激酶(U/L) 0.000 0.000 0.842 0.709 0.400 1.000 1.000~1.001
    TnT(μg/L) 0.619 1.040 0.595 0.354 0.552 1.857 0.242~14.263
    TnⅠ(μg/L) -0.092 0.252 -0.366 0.134 0.715 0.912 0.557~1.494
    dNLR -0.031 0.032 -0.984 0.967 0.325 0.969 0.911~1.032
    NLR 0.037 0.056 0.659 0.434 0.510 1.038 0.929~1.159
    SII 0.000 0.000 0.465 0.216 0.642 1.000 0.999~1.001
    SIRI -0.340 0.185 -1.837 3.375 0.066 0.712 0.495~1.023
    PLR 0.001 0.003 0.315 0.099 0.753 1.001 0.994~1.008
    MLR 1.618 1.181 1.369 1.875 0.171 5.041 0.498~51.062
    CRP、ESR、IL-6、PCT、TnT、Tn Ⅰ、dNLR、NLR、SII、SIRI、PLR、MLR:同表 1;McFadden R2=0.433;Cox & Snell R2=0.447;Nagelkerke R2=0.599
    下载: 导出CSV

    表  3  3006例Omicron BA.5.2感染住院患者疾病预后影响因素分析

    指标 回归系数 标准误 Z χ2 P OR 95% CI
    年龄(岁) 0.025 0.021 1.220 1.488 0.223 1.026 0.985~1.068
    住院天数(d) -0.990 1.114 -0.889 0.790 0.374 0.372 0.042~3.295
    血氧饱和度(%) 0.021 0.033 0.620 0.385 0.535 1.021 0.957~1.089
    CRP(mg/L) 0.008 0.003 2.214 4.902 0.027 1.008 1.001~1.015
    ESR(mm/h) -0.010 0.011 -0.860 0.739 0.390 0.990 0.969~1.012
    IL-6(ng/L) 0.000 0.000 0.927 0.860 0.354 1.000 1.000~1.001
    PCT(μg/L) -0.042 0.030 -1.419 2.013 0.156 0.959 0.904~1.016
    白蛋白(g/L) -0.069 0.047 -1.467 2.153 0.142 0.933 0.851~1.024
    球蛋白(g/L) -0.044 0.052 -0.850 0.723 0.395 0.957 0.864~1.059
    D-二聚体(mg/L) -0.034 0.046 -0.735 0.540 0.463 0.967 0.883~1.058
    肌酸激酶(U/L) 0.001 0.000 1.658 2.748 0.097 1.001 1.000~1.001
    TnT(μg/L) 0.053 1.267 0.042 0.002 0.967 1.055 0.088~12.622
    TnⅠ(μg/L) 0.428 0.284 1.507 2.271 0.132 1.534 0.879~2.676
    dNLR -0.172 0.112 -1.539 2.369 0.124 0.842 0.676~1.048
    NLR 0.075 0.059 1.275 1.625 0.202 1.078 0.960~1.211
    SII -0.001 0.001 -2.317 5.367 0.021 0.999 0.998~1.000
    SIRI 0.375 0.168 2.237 5.003 0.025 1.455 1.047~2.021
    PLR 0.006 0.004 1.389 1.929 0.165 1.006 0.998~1.014
    MLR -1.273 1.361 -0.935 0.874 0.350 0.280 0.019~4.036
    CRP、ESR、IL-6、PCT、TnT、Tn Ⅰ、dNLR、NLR、SII、SIRI、PLR、MLR:同表 1;McFadden R2=0.391;Cox & Snell R2=0.273;Nagelkerke R2=0.490
    下载: 导出CSV

    表  4  3006例Omicron BA.5.2感染住院患者疾病严重程度诊断预测价值

    指标 AUC 95% CI 标准误 P
    年龄(岁) 0.648 0.533~0.762 0.058 0.012
    住院天数(d) 0.493 0.372~0.613 0.061 0.906
    血氧饱和度(%) 0.461 0.339~0.582 0.062 0.523
    CRP(mg/L) 0.830 0.751~0.909 0.040 <0.001
    ESR(mm/h) 0.662 0.553~0.770 0.055 0.004
    IL-6(ng/L) 0.757 0.660~0.853 0.049 <0.001
    PCT(μg/L) 0.691 0.584~0.799 0.055 <0.001
    白蛋白(g/L) 0.249 0.151~0.346 0.050 <0.001
    球蛋白(g/L) 0.613 0.494~0.732 0.061 0.063
    D-二聚体(mg/L) 0.777 0.685~0.868 0.047 <0.001
    肌酸激酶(U/L) 0.529 0.409~0.649 0.061 0.634
    TnT(μg/L) 0.692 0.589~0.795 0.053 <0.001
    TnⅠ(μg/L) 0.683 0.577~0.790 0.054 0.001
    dNLR 0.511 0.376~0.646 0.069 0.875
    NLR 0.706 0.592~0.821 0.058 <0.001
    SII 0.658 0.542~0.773 0.059 0.007
    SIRI 0.636 0.523~0.749 0.058 0.019
    PLR 0.643 0.524~0.761 0.060 0.018
    MLR 0.643 0.526~0.760 0.060 0.016
    CRP、ESR、IL-6、PCT、TnT、Tn Ⅰ、dNLR、NLR、SII、SIRI、PLR、MLR: 同表 1; AUC: 曲线下面积
    下载: 导出CSV

    表  5  3006例Omicron BA.5.2感染住院患者疾病预后预测价值

    指标 AUC 95% CI 标准误 P
    年龄(岁) 0.590 0.409~0.770 0.092 0.330
    住院天数(d) 0.267 0.098~0.435 0.086 0.007
    血氧饱和度(%) 0.332 0.180~0.485 0.078 0.031
    CRP(mg/L) 0.805 0.697~0.914 0.055 <0.001
    ESR(mm/h) 0.668 0.491~0.845 0.090 0.063
    IL-6(ng/L) 0.836 0.724~0.949 0.057 <0.001
    PCT(μg/L) 0.770 0.624~0.916 0.075 <0.001
    白蛋白(g/L) 0.168 0.071~0.265 0.050 <0.001
    球蛋白(g/L) 0.509 0.318~0.699 0.097 0.928
    D-二聚体(mg/L) 0.875 0.800~0.950 0.038 <0.001
    肌酸激酶(U/L) 0.612 0.426~0.798 0.095 0.239
    TnT(μg/L) 0.760 0.624~0.897 0.070 <0.001
    TnⅠ(μg/L) 0.774 0.655~0.894 0.061 <0.001
    dNLR 0.463 0.264~0.662 0.102 0.715
    NLR 0.767 0.624~0.909 0.073 <0.001
    SII 0.704 0.547~0.861 0.080 0.011
    SIRI 0.662 0.506~0.818 0.080 0.042
    PLR 0.741 0.564~0.917 0.090 0.007
    MLR 0.784 0.636~0.933 0.076 <0.001
    CRP、ESR、IL-6、PCT、TnT、Tn Ⅰ、dNLR、NLR、SII、SIRI、PLR、MLR:同表 1
    下载: 导出CSV
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  • 收稿日期:  2023-02-03
  • 录用日期:  2023-04-03
  • 刊出日期:  2023-09-30

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