重症新型冠状病毒肺炎患者外周血D-二聚体水平、淋巴细胞亚群特征及细胞因子谱：一项系统评价和荟萃分析

D-dimer levels and characteristics of lymphocyte subsets, cytokine profiles in peripheral blood of patients with severe COVID-19: A systematic review and meta-analysis.

作者信息

Zhang Haiyue, Wu Huajun, Pan Dongli, Shen Weifeng

机构信息

Department of Clinical Laboratory, The First Hospital of Jiaxing and The Affiliated Hospital of Jiaxing University, Jiaxing, China.

出版信息

Front Med (Lausanne). 2022 Oct 5;9:988666. doi: 10.3389/fmed.2022.988666. eCollection 2022.

PURPOSE

A series of complications caused by severe COVID-19 can significantly affect short-term results. Therefore, early diagnosis is essential for critically COVID-19 patients. we aimed to investigate the correlation among D-dimer levels, lymphocyte subsets, cytokines, and disease severity in COVID-19 patients.

METHODS

Systematic review and meta- analysis of PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, Embase, clinical trials, and China National Knowledge Infrastructure (CNKI) until 1 August 2022. We considered case-control, and cohort studies that compared laboratory parameters between patients with severe or non-serious diseases or between survivors and non-survivors. Pooled data was assessed by use of a random-effects model and used to test heterogeneity. We assessed the risk of bias using the Newcastle- Ottawa Scale.

RESULTS

Of the 5,561 identified studies, 32 were eligible and included in our analysis ( = 3,337 participants). Random-effect results indicated that patients with COVID-19 in severe group had higher levels for D-dimer (WMD = 1.217 mg/L, 95%CI=[0.788, 1.646], < 0.001), neutrophil-to-lymphocyte ratio (NLR) (WMD = 6.939, 95%CI = [4.581, 9.297], < 0.001), IL-2 (WMD = 0.371 pg/ml, 95%CI = [-0.190, 0.932], = 0.004), IL-4 (WMD = 0.139 pg/ml, 95%CI = [0.060, 0.219], = 0.717), IL-6 (WMD = 44.251 pg/ml, 95%CI = [27.010, 61.493], < 0.001), IL-10 (WMD = 3.718 pg/ml, 95%CI = [2.648, 4.788], < 0.001) as well as lower levels of lymphocytes (WMD = -0.468( × 10/L), 95%CI = [-0.543, -0.394], < 0.001), T cells (WMD = -446.746(/μL), 95%CI = [-619.607, -273.885], < 0.001), B cells (WMD = -60.616(/μL), 95%CI = [-96.452, -24.780], < 0.001), NK cells (WMD = -68.297(/μL), 95%CI = [-90.600, -45.994], < 0.001), CD3+T cells (WMD = -487.870(/μL), 95%CI = [-627.248, -348.492], < 0.001), CD4+T cells (WMD = -290.134(/μL), 95%CI = [-370.834, -209.435], < 0.001), CD8+T cells (WMD = -188.781(/μL), 95%CI = [-227.806, -149.757], < 0.001).

CONCLUSIONS

There is a correlation among higher levels of D-dimer, cytokines, lower levels of lymphocyte subsets, and disease severity in COVID-19 patients. These effective biomarkers may help clinicians to evaluate the severity and prognosis of COVID-19. This study is registered with PROSPERO, number CRD42020196659.

SYSTEMATIC REVIEW REGISTRATION

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=196659; PROSPERO registration number: CRD42020196659.

目的

严重新型冠状病毒肺炎（COVID-19）引发的一系列并发症会显著影响短期预后。因此，早期诊断对于危重型COVID-19患者至关重要。我们旨在研究COVID-19患者D-二聚体水平、淋巴细胞亚群、细胞因子与疾病严重程度之间的相关性。

方法

截至2022年8月1日，对PubMed、Scopus、Web of Science、Cochrane对照试验中心注册库、Embase、临床试验及中国知网（CNKI）进行系统综述和荟萃分析。我们纳入了比较重症或非重症患者之间或幸存者与非幸存者之间实验室参数的病例对照研究和队列研究。采用随机效应模型评估合并数据，并用于检验异质性。我们使用纽卡斯尔-渥太华量表评估偏倚风险。

结果

在5561项检索到的研究中，32项符合纳入标准并纳入我们的分析（n = 3337名参与者）。随机效应结果表明，COVID-19重症组患者的D-二聚体水平更高（加权均数差[WMD]=1.217mg/L，95%置信区间[CI]=[0.788, 1.646]，P<0.001）、中性粒细胞与淋巴细胞比值（NLR）更高（WMD = 6.939，95%CI = [4.581, 9.297]，P<0.001）、白细胞介素-2（IL-2）更高（WMD = 0.371pg/ml，95%CI = [-0.190, 0.932]；P = 0.004）、IL-4更高（WMD = 0.139pg/ml，95%CI = [0.060, 0.219]，P = 0.717）、IL-6更高（WMD = 44.251pg/ml，95%CI = [27.010, 61.493]，P<0.001）、IL-10更高（WMD = 3.718pg/ml，95%CI = [2.648, 4.788]，P<0.001），而淋巴细胞水平更低（WMD = -0.468(×10⁹/L)，95%CI = [-0.543, -0.394]，P<0.001）、T细胞水平更低（WMD = -446.746(/μL)，95%CI = [-619.607, -273.885]；P<0.001）、B细胞水平更低（WMD = -60.616(/μL)，95%CI = [-96.452, -24.780]，P<0.001）、自然杀伤细胞（NK细胞）水平更低（WMD = -68.297(/μL)，95%CI = [-90.600, -45.994]，P<0.001）、CD3⁺T细胞水平更低（WMD = -487.870(/μL)，95%CI = [-627.248, -348.492]，P<0.001）、CD4⁺T细胞水平更低（WMD = -290.134(/μL)，95%CI = [-370.834, -209.435]，P<0.001）、CD8⁺T细胞水平更低（WMD = -188.781(/μL)，95%CI = [-227.806, -149.757]，P<0.001）。