Immune Phenotyping Based on the Neutrophil-to-Lymphocyte Ratio and IgG Level Predicts Disease Severity and Outcome for Patients With COVID-19
Immune Phenotyping Based on the Neutrophil-to-Lymphocyte Ratio and IgG Level Predicts Disease Severity and Outcome for Patients With COVID-19
复制标题
DOI：
10.3389/fmolb.2020.00157
复制
发表时间：
2020-07-03
影响因子：
5
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Zhang, Bicheng;Zhou, Xiaoyang;Wang, Jun
导读：最近一种名为2019冠状病毒病（COVID-19）的呼吸道疾病迅速在全球蔓延。这种疾病是由严重急性呼吸道综合征冠状病毒-2（SARS-CoV-2）和不受控制的细胞因子风暴引发的，但目前尚不清楚强大的抗体反应是否与COVID-19患者的临床恶化和不良结局有关。方法：采用化学发光分析法（CLIA）检测武汉市某中心COVID-19患者血清中SARS-CoV-2 IgG和IgM抗体。计算所有入选患者急性期和恢复期血清（35天内）中的中位IgG和IgM水平，并在重度和非重度患者之间进行比较。基于晚期IgG水平和嗜中性粒细胞与淋巴细胞比率（NLR）的免疫应答表型特征，将患者分为不同的疾病严重程度和结局。结果：共有222例患者纳入本研究。IgG在发病第4天首次检测到，其峰值水平出现在第四周。与IgG水平低的患者相比，IgG水平高的患者中更常见重度病例（51.8% vs. 32.3%;p= 0.008）。具有NLR（hi）IgG（hi）、NLR（hi）IgG（lo）、NLR（lo）IgG（hi）和NLR（lo）IgG（lo）表型的患者的严重率分别为72.3%、48.5%、33.3%和15.6%（p< 0.0001）。NLR（hi）IgG（hi）、NLR（hi）IgG（lo）型重症患者IL-2、IL-6、IL-10等炎性细胞因子水平明显高于NLR（lo）IgG（lo）型患者（p< 0.05），CD 4 + T细胞计数明显低于NLR（lo）型患者（p< 0.05）。NLR（hi）IgG（hi）、NLR（hi）IgG（lo）、NLR（lo）IgG（hi）和NLR（lo）IgG（lo）表型的重症患者的恢复率分别为58.8%（20/34）、68.8%（11/16）、80.0%（4/5）和100%（12/12）（p= 0.0592）。死亡病例仅发生在NLR（hi）IgG（hi）和NLR（hi）IgG（lo）表型。结论：COVID-19严重程度与IgG应答增加相关，基于晚期IgG应答和NLR的免疫应答表型可以作为区分严重和非严重COVID-19患者的简单补充工具，并进一步预测其临床结局。
Introduction:A recently emerging respiratory disease named coronavirus disease 2019 (COVID-19) has quickly spread across the world. This disease is initiated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and uncontrolled cytokine storm, but it remains unknown as to whether a robust antibody response is related to clinical deterioration and poor outcome in COVID-19 patients. Methods:Anti-SARS-CoV-2 IgG and IgM antibodies were determined by chemiluminescence analysis (CLIA) in COVID-19 patients at a single center in Wuhan. Median IgG and IgM levels in acute and convalescent-phase sera (within 35 days) for all included patients were calculated and compared between severe and non-severe patients. Immune response phenotyping based on the late IgG levels and neutrophil-to-lymphocyte ratio (NLR) was characterized to stratified patients into different disease severities and outcomes. Results:A total of 222 patients were included in this study. IgG was first detected on day 4 of illness, and its peak levels occurred in the fourth week. Severe cases were more frequently found in patients with high IgG levels, compared to those with low IgG levels (51.8 vs. 32.3%;p= 0.008). Severity rates for patients with NLR(hi)IgG(hi), NLR(hi)IgG(lo), NLR(lo)IgG(hi), and NLR(lo)IgG(lo)phenotype were 72.3, 48.5, 33.3, and 15.6%, respectively (p< 0.0001). Furthermore, severe patients with NLR(hi)IgG(hi), NLR(hi)IgG(lo)had higher inflammatory cytokines levels including IL-2, IL-6 and IL-10, and decreased CD4+ T cell count compared to those with NLR(lo)IgG(lo)phenotype (p< 0.05). Recovery rates for severe patients with NLR(hi)IgG(hi), NLR(hi)IgG(lo), NLR(lo)IgG(hi), and NLR(lo)IgG(lo)phenotype were 58.8% (20/34), 68.8% (11/16), 80.0% (4/5), and 100% (12/12), respectively (p= 0.0592). Dead cases only occurred in NLR(hi)IgG(hi)and NLR(hi)IgG(lo)phenotypes. Conclusions:COVID-19 severity is associated with increased IgG response, and an immune response phenotyping based on the late IgG response and NLR could act as a simple complementary tool to discriminate between severe and non-severe COVID-19 patients, and further predict their clinical outcome.