Immune Phenotyping Based on the Neutrophil-to-Lymphocyte Ratio and IgG Level Predicts Disease Severity and Outcome for Patients With COVID-19.,Frontiers in Molecular Biosciences

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Immune Phenotyping Based on the Neutrophil-to-Lymphocyte Ratio and IgG Level Predicts Disease Severity and Outcome for Patients With COVID-19.
Frontiers in Molecular Biosciences ( IF 3.9 ) Pub Date : 2020-06-22 , DOI: 10.3389/fmolb.2020.00157
Bicheng Zhang ₁ , Xiaoyang Zhou ₂ , Chengliang Zhu ₃ , Yuxiao Song ₁ , Fan Feng ₁ , Yanru Qiu ₁ , Jia Feng ₁ , Qingzhu Jia ₄ , Qibin Song ₁ , Bo Zhu ₄ , Jun Wang ₅

Affiliation

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^hiIgG^hi, NLR^hiIgG^lo, NLR^loIgG^hi, and NLR^loIgG^lo phenotype were 72.3, 48.5, 33.3, and 15.6%, respectively (p < 0.0001). Furthermore, severe patients with NLR^hiIgG^hi, NLR^hiIgG^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^loIgG^lo phenotype (p < 0.05). Recovery rates for severe patients with NLR^hiIgG^hi, NLR^hiIgG^lo, NLR^loIgG^hi, and NLR^loIgG^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^hiIgG^hi and NLR^hiIgG^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.

中文翻译：

基于中性粒细胞与淋巴细胞比率和 IgG 水平的免疫表型可预测 COVID-19 患者的疾病严重程度和结果。

介绍：最近出现的一种名为 2019 冠状病毒病 (COVID-19) 的呼吸道疾病已在世界范围内迅速传播。这种疾病是由严重急性呼吸综合征冠状病毒-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预后有关。

方法：在武汉的一个中心，通过化学发光分析 (CLIA) 对 COVID-19 患者进行了抗 SARS-CoV-2 IgG 和 IgM 抗体的测定。计算所有纳入患者的急性期和恢复期血清（35 天内）的中位 IgG 和 IgM 水平，并在重症和非重症患者之间进行比较。基于晚期 IgG 水平和中性粒细胞与淋巴细胞比率 (NLR) 的免疫反应表型分析可将患者分为不同的疾病严重程度和结果。

结果：本研究总共纳入 222 名患者。 IgG 在患病第 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，高 IgG 水平的患者更容易发现重症病例（51.8% vs. 32.3%； p = 0.008）。 NLR ^hi IgG ^hi 、NLR ^hi IgG ^lo 、NLR ^lo IgG ^hi和 NLR ^lo IgG ^lo表型患者的严重率分别为 72.3%、48.5%、33.3% 和 15.6%（ p < 0.0001)。此外，与 NLR ^lo IgG ^lo表型患者相比，NLR ^hi IgG ^hi 、NLR ^hi IgG ^lo重症患者的炎症细胞因子水平较高，包括 IL-2、IL-6 和 IL-10，并且 CD4+ T 细胞计数减少。 p < 0.05）。 NLR ^hi IgG ^hi 、NLR ^hi IgG ^lo 、NLR ^lo IgG ^hi 、NLR ^lo IgG ^lo表型的重症患者康复率分别为 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表型中。