海军军医大学学报  2022, Vol. 43 Issue (9): 1037-1043   PDF    
引用本文
董旭, 徐爱静, 葛玲玲, 陈怡, 杨明, 薛建亚. 高龄奥密克戎变异株感染者血清白细胞介素6的临床意义及与合并基础疾病的相关性[J]. 海军军医大学学报, 2022, 43(9): 1037-1043  
DONG Xu, XU Ai-jing, GE Ling-ling, CHEN Yi, YANG Ming, XUE Jian-ya. Clinical significance of serum interleukin 6 in elderly patients infected with severe acute respiratory syndrome coronavirus 2 omicron variant and its correlation with underlying diseases[J]. Academic Journal of Naval Medical University, 2022, 43(9): 1037-1043 (in Chinese with English abstract)  
高龄奥密克戎变异株感染者血清白细胞介素6的临床意义及与合并基础疾病的相关性
董旭1△, 徐爱静1△, 葛玲玲1, 陈怡1, 杨明2, 薛建亚1     
1. 海军军医大学（第二军医大学）第一附属医院感染科，上海 200433;
2. 海军军医大学（第二军医大学）第一附属医院内科规培基地，上海 200433
收稿日期: 2022-06-15    接受日期: 2022-08-15
作者简介: 董旭，硕士生，住院医师.E-mail: yxdongxu@126.com;
徐爱静，硕士，主治医师.E-mail: xuaijing86@163.com.
通信作者(Corresponding author): 薛建亚, Tel: 021-31161909, E-mail: jyxue@163.com.
△共同第一作者（Co-first authors）.
摘要: 目的 探究血清IL-6在高龄奥密克戎变异株感染者中的临床意义，以及合并基础疾病与血清IL-6水平的相关性。方法 纳入2022年4－6月入住海军军医大学（第二军医大学）第一附属医院感染科、严重急性呼吸综合征冠状病毒2 RNA检测呈阳性的高龄（＞80岁）奥密克戎变异株感染患者22例，采用流式细胞学检测法测定血清IL-6水平，采用免疫比浊法测定CRP水平。根据影像学检查有无肺炎表现将患者分为肺炎组（16例）和无肺炎组（6例），根据病情分为重症组（重型和危重型，5例）和非重症组（轻型和普通型，17例），采用二分类logistic回归模型和ROC曲线分析血清IL-6、CRP水平与病情严重程度和是否进展为肺炎的相关性，同时探究合并基础疾病与血清IL-6水平的关系。结果 22例患者中轻型6例、普通型11例、重型3例、危重型2例。肺炎组基线血清IL-6水平高于无肺炎组[（20.16±12.36）pg/mL vs（5.42±1.57）pg/mL，P＝0.009]，肺炎组和无肺炎组基线血清CRP水平差异无统计学意义（P＞0.05）；重症组和非重症组基线血清IL-6和CRP水平差异均无统计学意义（P均＞0.05）。logistic回归分析显示，基线血清IL-6、CRP水平可能与感染奥密克戎变异株后进展为肺炎有关，但均无统计学意义（OR＝2.407，95% CI 0.915~6.328；OR＝1.030，95% CI 0.952~1.114）；ROC曲线分析显示，基线血清IL-6、CRP预测患者进展为肺炎的AUC值分别为0.969（95% CI 0.900~1.000）、0.656（95% CI 0.380~0.932），两者AUC值差异有统计学意义（Z＝2.154，P＝0.030）。有无高血压病、糖尿病、冠心病、慢性肾脏病、慢性阻塞性肺疾病的患者基线血清IL-6水平、重症患者占比、肺炎患者占比差异均无统计学意义（P均＞0.05）。合并1种、2种、3种及以上基础疾病的高龄奥密克戎变异株感染者基线血清IL-6水平分别为12.50（9.15，21.75）、23.55（9.63，50.10）、10.90（5.20，18.88）pg/mL，差异无统计学意义（P＞0.05）。结论 在奥密克戎变异株感染患者中，有肺炎表现者血清IL-6水平明显增高且与病情进展有关，对高龄新型冠状病毒肺炎患者病情判断、疗效及预后评估有重要的指导意义。
关键词: 80岁以上老年人    新型冠状病毒肺炎    奥密克戎变异株    严重急性呼吸综合征冠状病毒2    白细胞介素6    基础疾病    
Clinical significance of serum interleukin 6 in elderly patients infected with severe acute respiratory syndrome coronavirus 2 omicron variant and its correlation with underlying diseases
DONG Xu1△, XU Ai-jing1△, GE Ling-ling1, CHEN Yi1, YANG Ming2, XUE Jian-ya1     
1. Department of Infectious Diseases, The First Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200433, China;
2. Internal Medicine Training Base, The First Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200433, China
Abstract: Objective To investigate the clinical significance of serum interleukin 6 (IL-6) in elderly patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant and its correlation with underlying diseases. Methods A total of 22 elderly patients (> 80 years old) infected with omicron variant, who were admitted to Department of Infectious Diseases, The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from Apr. to Jun. 2022 and tested positive for SARS-CoV-2 RNA, were included. The level of serum IL-6 was measured by flow cytometry, and the level of serum C reactive protein (CRP) was measured by immunonephelometry. Patients were divided into pneumonia group (16 cases) and non-pneumonia group (6 cases) according to the imaging examination results, and were divided into severe group (severe and critical type, 5 cases) and non-severe group (mild and normal type, 17 cases) according to the condition. Binary logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the correlation between serum IL-6 and CRP levels and the severity of the disease and whether it would progress to pneumonia. Meanwhile, the relationships between underlying diseases and serum IL-6 level were explored. Results Among the 22 patients, 6 were mild, 11 were normal, 3 were severe, and 2 were critical. The baseline serum IL-6 level in the pneumonia group was significantly higher than that in the non-pneumonia group ([20.16±12.36] pg/mL vs [5.42±1.57] pg/mL, P＝0.009), and there was no significant difference in baseline serum CRP level between the 2 groups (P > 0.05). There were no significant differences in baseline serum IL-6 or CRP levels between the severe group and the non-severe group (both P > 0.05). Logistic regression analysis showed that the baseline serum IL-6 and CRP might be related to pneumonia after infection with omicron variant (odds ratio [OR]＝2.407, 95% confidence interval [CI] 0.915-6.328; OR＝1.030, 95% CI 0.952-1.114). ROC curve analysis showed that the area under curve values of serum IL-6 and CRP in predicting the progression to pneumonia were 0.969 (95% CI 0.900-1.000) and 0.656 (95% CI 0.380-0.932), respectively, with statistical significance (Z＝2.154, P＝0.030). There were no significant differences in the baseline serum IL-6 level or proportions of severe patients or pneumonia patients among patients with or without hypertension, diabetes mellitus, coronary heart disease, chronic kidney disease or chronic obstructive pulmonary disease (all P > 0.05). The baseline serum IL-6 levels of the omicron variant infected elderly patients with 1, 2, and 3 or more underlying diseases were 12.50 (9.15, 21.75), 23.55 (9.63, 50.10), and 10.90 (5.20, 18.88) pg/mL, respectively, with no statistical significance (P > 0.05). Conclusion For omicron variant infected patients, serum IL-6 level is significantly increased in patients with pneumonia manifestations and is correlated with disease progression. Serum IL-6 level is of great guiding significance to judge disease progression and evaluate efficacy and prognosis of elderly coronavirus disease 2019 patients.
Key words: aged 80 years over    coronavirus disease 2019    omicron variant    severe acute respiratory syndrome coronavirus 2    interleukin 6    underlying diseases    

新型冠状病毒肺炎（coronavirus disease 2019，COVID-19）是由严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）感染导致的肺部炎症，自2019年12月暴发以来已成为国际公共卫生紧急事件[1]。COVID-19患者随着病情进展可出现致死性肺部炎症和肺外表现，如血栓栓塞、心肌损伤、肾功能衰竭等[2]。当前COVID-19疫情仍在世界范围内持续流行，奥密克戎（omicron）变异株已成为近期全球COVID-19疫情的主要流行株。我国COVID-19临床分型分为轻型、普通型、重型和危重型，病程中往往依据血清学、影像学及临床症状等判断病情和预后，其中血清学监测指标主要包括白细胞计数、淋巴细胞计数、CRP、红细胞沉降率等[3]。

IL-6作为一种关键促炎介质，可导致炎症反应迅速加重并诱导CRP和降钙素原合成。一项回顾性研究结果显示IL-6水平升高与COVID-19病情严重程度有关，高龄、合并糖尿病或IL-6水平明显增高的COVID-19患者更易进展为重型[4]。高龄人群由于免疫力下降，营养状态相对较差，往往伴有多种基础疾病，在感染SARS-CoV-2后进展为肺炎甚至重型、危重型的概率较高[5]，关注高龄COVID-19患者、尽早预测疾病的严重程度将对治疗决策和患者预后产生积极影响。本研究探讨高龄奥密克戎变异株感染者入院后基线血清IL-6水平、病情变化后IL-6的变化趋势、IL-6异常高表达与病情严重程度的相关性，并分析合并基础疾病对IL-6水平的影响。

1 资料和方法 1.1 病例资料

采用回顾性研究设计，选择2022年4－6月入住海军军医大学（第二军医大学）第一附属医院感染科且SARS-CoV-2 RNA检测呈阳性的高龄奥密克戎变异株感染者26例。纳入标准：（1）年龄＞80岁；（2）COVID-19的诊断符合《新型冠状病毒肺炎诊疗方案（试行第九版）》[3]，口咽拭子和鼻咽拭子SARS-CoV-2 RNA检测阳性，且基因测序结果提示病毒为奥密克戎变异株；（3）合并至少1种基础疾病，包括高血压病、2型糖尿病、冠心病、慢性肾脏病和慢性阻塞性肺疾病。排除标准：（1）COVID-19复阳患者；（2）免疫功能缺陷（如长期使用糖皮质激素或其他免疫抑制剂导致免疫功能减退）患者；（3）入院时SARS-CoV-2 RNA检出阳性超过3 d，无法取得感染后基线值（感染至入院3 d内首次检测结果）。排除无基础疾病患者1例、长期口服免疫抑制剂患者1例、入院时SARS-CoV-2 RNA检出阳性1周患者2例，共22例患者纳入研究。本研究通过海军军医大学（第二军医大学）第一附属医院伦理委员会审批（CHEC2022-111）。

1.2 研究方法

根据病情需要，入院后次日晨起及之后每3 d采集患者肘正中静脉血5 mL，根据病情变化必要时增加采血频率，送检验科常温3 000 r/min（离心半径为15.7 cm，湖南湘仪实验室仪器开发有限公司L-1550型离心机）离心10 min取血清，利用美国BD公司FACSCantoⅡ分析型流式细胞仪通过流式细胞学检测法测定IL-6水平，检测过程严格按照细胞因子联合检测试剂盒（货号6971711320005，规格100人份/盒，美国BD公司）说明书进行，IL-6正常参考值为0~10 pg/mL。利用美国BECKMAN COULTER有限公司AU5800型全自动生化分析仪，通过免疫比浊法测定CRP水平，试剂、校准品均由美国BECKMAN COULTER有限公司提供，CRP正常参考值为0~10 mg/L。所有检测操作均由专业人员严格按照防护标准进行，避免感染。

1.3 统计学处理

应用SPSS 23.0软件进行统计学分析。对计量资料进行正态性检验（Kolmogorov-Smirnov检验、P-P图）和方差齐性检验（F检验），若呈正态分布以x±s表示，两组间比较采用独立样本t检验；若呈偏态分布则以中位数（下四分位数，上四分位数）表示，两组间比较采用Mann-Whitney U检验，多个样本间比较采用Kruskal-Wallis H检验。计数资料以例数和百分数表示，两组间比较采用χ2检验或Fisher确切概率法。采用二分类logistic回归模型分析基线血清IL-6、CRP水平与奥密克戎变异株感染患者病情严重程度或是否进展至肺炎的相关性，绘制ROC曲线分析单一指标及联合指标对高龄奥密克戎变异株感染患者重症化的预测价值，采用Z检验比较2种指标的AUC值。检验水准（α）为0.05。

2 结果 2.1 基本情况

22例高龄奥密克戎变异株感染患者中男10例、女12例，年龄为83~95岁，轻型6例、普通型11例、重型3例、危重型2例。根据病程中影像学检查有无肺炎表现分为肺炎组和无肺炎组，其中肺炎组16例（普通型11例、重型3例、危重型2例），男6例、女10例，年龄为83~95岁，平均年龄为（89.5±3.7）岁；无肺炎组6例（均为轻型），男4例、女2例，年龄为86~95岁，平均年龄为（90.2±3.3）岁。肺炎组与无肺炎组患者的年龄、性别构成差异均无统计学意义（P均＞0.05）。

根据病情分为重症（重型及危重型）组和非重症（轻型及普通型）组，其中重症组5例，男3例、女2例，年龄为87~95岁，平均年龄为（90.8±3.0）岁；非重症组17例，男7例、女10例，年龄为83~95岁，平均年龄为（89.4±3.7）岁。重症组与非重症组患者的年龄、性别构成差异均无统计学意义（P均＞0.05）。

2.2 不同分组患者的基线血清IL-6及CRP水平比较

肺炎组患者的基线血清IL-6水平为（20.16±12.36）pg/mL，无肺炎组为（5.42±1.57）pg/mL，差异有统计学意义（t＝2.302，P＝0.009）。重症组患者的基线血清IL-6水平为17.60（10.90，51.45）pg/mL，非重症组为12.50（5.90，23.55）pg/mL，差异无统计学意义（P＞0.05）。肺炎组患者基线血清CRP水平为9.65（3.78，21.98）mg/L，无肺炎组为4.85（1.43，14.03）mg/L，差异无统计学意义（P＞0.05）。重症组患者基线血清CRP水平为15.3（2.75，64.25）mg/L，非重症组为6.20（2.75，16.65）mg/L，差异无统计学意义（P＞0.05）。

2.3 重症组患者血清IL-6水平随病情进展进行性升高

重症组5例患者中，3例于入院后第3天出现气促、乏力，之后随访胸部CT平扫未见明显间质性改变，无胸腔积液；1例于入院后第6天出现乏力症状，第9天出现少量胸腔积液，并于第12天出现血氧饱和度进行性下降，胸部CT平扫提示肺部间质性改变、炎性渗出明显增多；1例于入院第9天出现气促、呼吸困难，监测血氧饱和度下降。该5例患者IL-6水平均呈进行性升高。典型病例随病情进展的影像学表现及IL-6指标变化见图 1。

图 1 2例高龄奥密克戎变异株感染患者的影像学表现及血清IL-6水平变化 Fig 1 Imaging and changes of serum IL-6 levels in 2 elderly patients infected with SARS-CoV-2 omicron variant A: A patient (male, 91-year-old) was admitted to the hospital on Apr. 14, 2022, without complaints of fever, sore throat, dyspnea, or other discomfort. On Apr. 15, chest CT plain scan showed clear lung texture, and the serum IL-6 level was 11.2 pg/mL. On Apr. 20, the patient developed fatigue, chest CT plain scan showed a little patchy new inflammation near the pleura of both lungs, and the serum IL-6 level was 22.1 pg/mL. On Apr. 26, the patient developed dyspnea with decreased oxygen saturation (83%), chest CT plain scan showed significantly aggravated pulmonary inflammation, so the clinical classification was critical type, and the serum IL-6 level was 1 618.4 pg/mL. The patient received tocilizumab, an IL-6 inhibitor, for 3 d (from Apr. 26 to Apr. 28), and the serum IL-6 level significantly decreased on Apr. 29. B: A patient (female, 88-year-old), who was bedridden due to liver cirrhosis and Alzheimer disease, was admitted on May 2, 2022, without respiratory symptoms. On May 13, the patient developed short breath and dyspnea, and the oxygen saturation fluctuated between 88%-92% (without oxygen inhalation); chest CT plain scan showed multiple grid-like density in both lungs, especially in the lower lobe; and the serum IL-6 level was 185.4 pg/mL. On May 18, chest CT plain scan showed obvious aggravation of inflammation, so the patient was classified as critical type; and the serum IL-6 level was 1 740.7 pg/mL. IL-6: Interleukin 6; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; CT: Computed tomography.

2.4 IL-6、CRP单一及联合检测与高龄奥密克戎变异株感染患者肺部炎症和病情严重程度的相关性 2.4.1 IL-6、CRP与肺部炎症的相关性

以奥密克戎变异株感染患者肺部炎症程度为因变量（肺炎赋值为1，无肺炎赋值为0），以基线血清IL-6、CRP水平为自变量进行二分类logistic回归拟合，Hosmer-Lemeshow检验结果提示回归模型和真实数据拟合良好（P＞0.05）；logistic回归分析结果显示，基线血清IL-6、CRP可能是感染奥密克戎变异株后进展为肺炎的潜在预测因素，但均无统计学意义（OR＝2.407，95% CI 0.915~6.328，P＝0.075；OR＝1.030，95% CI 0.952~1.114，P＝0.462）。ROC曲线分析结果（图 2）显示，基线血清IL-6、CRP水平预测患者进展为肺炎的AUC值分别为0.969（95% CI 0.900~1.000）、0.656（95% CI 0.380~0.932），基线血清IL-6预测患者入院后进展为肺炎的效果优于基线血清CRP（Z＝2.154，P＝0.030）。

图 2 基线血清IL-6、CRP预测高龄奥密克戎变异株感染患者进展为肺炎的ROC曲线 Fig 2 ROC curve of baseline serum IL-6 and CRP in predicting pulmonary inflammation in elderly patients infected with SARS-CoV-2 omicron variant IL-6: Interleukin 6; CRP: C reactive protein; ROC: Receiver operating characteristic; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; AUC: Area under curve.

2.4.2 IL-6、CRP与病情严重程度的相关性

以高龄奥密克戎变异株感染患者病情严重程度为因变量（重症赋值为1，非重症赋值为0），以基线血清IL-6、CRP水平为自变量进行二分类logistic回归拟合，Hosmer-Lemeshow检验结果提示回归模型和真实数据拟合良好（P＞0.05）；logistic回归分析结果显示，基线血清IL-6、CRP水平在预测病情严重程度方面均无统计学意义（OR＝1.033，95% CI 0.981~1.087，P＝0.222；OR＝1.033，95% CI 0.983~1.084，P＝0.196）。

2.5 基础疾病与基线血清IL-6水平的相关性

根据患者有无高血压病、糖尿病、冠心病、慢性肾脏病、慢性阻塞性肺疾病各分为两组，因分组后病例数较少不能进行正态性检验，IL-6水平均使用中位数（下四分位数，上四分位数）描述，有、无上述5种疾病的患者血清IL-6水平、重症患者占比、肺炎患者占比差异均无统计学意义（P均＞0.05，表 1）。合并1种、2种、3种及以上基础疾病的高龄奥密克戎变异株感染患者分别有6、8、8例，基线血清IL-6水平分别为12.50（9.15，21.75）、23.55（9.63，50.10）、10.90（5.20，18.88）pg/mL，差异无统计学意义（P＞0.05）。

表 1 高龄奥密克戎变异株感染患者基础疾病患病情况与基线血清IL-6水平的关系 Tab 1 Relationship between prevalence of underlying diseases and baseline serum IL-6 levels in elderly patients infected with SARS-CoV-2 omicron variant

3 讨论

IL-6是T淋巴细胞、内皮细胞和单核细胞等合成的促炎症细胞因子。炎症初期IL-6在局部病变部位合成后通过血流进入肝脏，随后迅速诱导生成大量急性期蛋白，如CRP、血清淀粉样蛋白A、纤维蛋白原等，还可以诱导分化并促进造血干细胞和肝细胞增殖[6]。感染SARS-CoV-2后患者疾病的发生、发展及重症化与体内淋巴细胞亚群紊乱、细胞因子风暴产生等免疫失衡有关，其中细胞免疫发挥了至关重要的作用[7]。SARS-CoV-2感染后T细胞被迅速激活而产生粒细胞-巨噬细胞集落刺激因子和IL-6等细胞因子，粒细胞-巨噬细胞集落刺激因子会进一步激活炎症性单核细胞，产生更多的IL-6和其他炎症因子，形成炎症风暴，导致严重的免疫损伤[8]。研究发现SARS-CoV-2感染者的IL-6水平相对较高，是患者生存预后的独立预测因素[9-10]。

本研究结果显示，对于高龄奥密克戎变异株感染者，肺炎组基线血清IL-6水平高于无肺炎组，而根据是否进展至重型甚至危重型分组的患者基线血清IL-6水平差异无统计学意义，可见无论后续病情是否会进展，入院后基线血清IL-6水平不会因患者有无重症化倾向而存在差异。虽然后续发生重症化的高龄患者入院后基线IL-6水平与非重症组相比差异无统计学意义，但IL-6水平与临床症状的严重程度相关，重症组患者随着病情进展（即逐渐出现气促、乏力等临床症状，血氧饱和度进行性下降，影像学检查提示肺间质性改变、炎性渗出明显增多等）IL-6水平持续升高。IL-6作为针对SARS-CoV-2感染后全身性过度炎症反应的免疫调节治疗靶点，本研究中有患者在连续3 d使用IL-6抑制剂托珠单抗治疗后检测血清IL-6水平即发现其明显降低。这与既往文献报道的应用IL-6抑制剂对重症COVID-19患者有利并可能降低其死亡率[11]相吻合。以上结果表明IL-6升高的程度与病情严重程度一致，一旦病情控制IL-6即会迅速下降，如果经过治疗后IL-6未明显下降可能提示患者预后不佳。

目前临床常用的炎症指标包括IL-6、CRP、降钙素原等。印度一家三级医院ICU开展的一项单中心回顾性研究发现，有氧合缺陷的成人COVID-19患者IL-6和CRP水平较高，而降钙素原变化不显著，入院时检测IL-6和CRP可在病程早期预测疾病的严重程度[12]。另一项研究显示，COVID-19死亡患者血清IL-6和CRP水平均高于存活患者，且与疾病的严重程度相关[13]。本研究结果显示，基线血清IL-6、CRP水平可能是高龄患者感染奥密克戎变异株后进展为肺炎的潜在预测因素（OR＝2.407、1.030），但差异无统计学意义，考虑为样本量太小使统计结果不稳定、产生较大的误差有关；同时ROC曲线分析显示基线血清IL-6、CRP预测患者进展为肺炎的AUC值分别为0.969、0.656，提示IL-6在预测高龄奥密克戎变异株感染患者是否进展至肺炎方面优于CRP，有更好的预测价值。

本研究数据显示，合并基础疾病对于高龄奥密克戎变异株感染者是否会进展至肺炎或重症化无明显影响，且合并不同基础疾病的患者之间血清IL-6水平差异均无统计学意义，这与多数文献分析结果不同。文献报道，合并高血压病、糖尿病、慢性肾脏病、肺部疾病、肿瘤等基础疾病的高龄人群是COVID-19进展至重型乃至危重型的高危人群，也是死亡率增加的重要原因[14]。高血压病已被证明与COVID-19患者死亡风险增加、需要重症监护及疾病进展有关[15]，SARS-CoV-2感染后IL-6增高可损伤血管内皮细胞，影响一氧化氮的生成并增加血液黏滞度，导致机体血压升高。由此可见，COVID-19本身会引起高血压，而高龄患者的基础高血压病可能加重肺炎。无论是1型还是2型糖尿病患者发生COVID-19后其病情严重程度和死亡率都显著增加[16]，同时COVID-19的存在也对糖尿病的治疗产生一定影响，可诱发高血糖或促使糖尿病病情进展[17]。COVID-19与心血管疾病也相互影响，有心血管疾病病史的高龄COVID-19患者病死率较高。彭明等[18]研究发现，合并冠心病的COVID-19患者较未合并冠心病的COVID-19患者血氧饱和度更低、重型比例更高；Lazzerini等[19]证实发生重型COVID-19时IL-6升高可促进心室电重构，他汀类药物的使用可下调IL-6、减轻炎症，提高COVID-19患者的存活率[20]。本研究数据未得到与既往研究相同的结果，考虑与纳入的高龄奥密克戎变异株感染者例数较少及单中心回顾性研究的局限性有关。此外，本研究纳入的高龄患者均合并至少1种基础疾病，而文献较多探讨的是青年组与老年组[21]或老年组与高龄组的比较[22]，对于病例之间是否存在基础疾病相差较大的情况不得而知。由于样本量较小，无法排除基础疾病影响COVID-19重症化对本研究结论造成的干扰。

IL-6作为早期识别奥密克戎变异株感染后病情严重程度和患者分层的有效指标，对临床治疗决策有明确意义[23]。伴有多种慢性基础疾病的高龄人群是重型或危重型COVID-19高危人群，一旦感染奥密克戎变异株其死亡率、重症率均较高，早期积极、有效干预对疾病转归有重要意义。在奥密克戎变异株感染者治疗过程中应关注血清IL-6的变化情况，预防重症化并早期干预，以改善患者预后、降低病死率。

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