严重和中度 COVID-19 患者的抗体和细胞因子谱存在差异。

Different Profiles of Antibodies and Cytokines Were Found Between Severe and Moderate COVID-19 Patients.

机构信息

Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

Institute of Laboratory Medicine, Jinling Hospital, Nanjing University School of Medicine, The First School of Clinical Medicine, Southern Medical University, Nanjing, China.

出版信息

Front Immunol. 2021 Aug 19;12:723585. doi: 10.3389/fimmu.2021.723585. eCollection 2021.

Abstract

OBJECTIVES

Our objective was to determine the antibody and cytokine profiles in different COVID-19 patients.

METHODS

COVID-19 patients with different clinical classifications were enrolled in this study. The level of IgG antibodies, IgA, IgM, IgE, and IgG subclasses targeting N and S proteins were tested using ELISA. Neutralizing antibody titers were determined by using a toxin neutralization assay (TNA) with live SARS-CoV-2. The concentrations of 8 cytokines, including IL-2, IL-4, IL-6, IL-10, CCL2, CXCL10, IFN-γ, and TNF-α, were measured using the Protein Sample Ella-Simple ELISA system. The differences in antibodies and cytokines between severe and moderate patients were compared by t-tests or Mann-Whitney tests.

RESULTS

A total of 79 COVID-19 patients, including 49 moderate patients and 30 severe patients, were enrolled. Compared with those in moderate patients, neutralizing antibody and IgG-S antibody titers in severe patients were significantly higher. The concentration of IgG-N antibody was significantly higher than that of IgG-S antibody in COVID-19 patients. There was a significant difference in the distribution of IgG subclass antibodies between moderate patients and severe patients. The positive ratio of anti-S protein IgG3 is significantly more than anti-N protein IgG3, while the anti-S protein IgG4 positive rate is significantly less than the anti-N protein IgG4 positive rate. IL-2 was lower in COVID-19 patients than in healthy individuals, while IL-4, IL-6, CCL2, IFN-γ, and TNF-α were higher in COVID-19 patients than in healthy individuals. IL-6 was significantly higher in severe patients than in moderate patients. The antibody level of anti-S protein was positively correlated with the titer of neutralizing antibody, but there was no relationship between cytokines and neutralizing antibody.

CONCLUSIONS

Our findings show the severe COVID-19 patients' antibody levels were stronger than those of moderate patients, and a cytokine storm is associated with COVID-19 severity. There was a difference in immunoglobulin type between anti-S protein antibodies and anti-N protein antibodies in COVID-19 patients. And clarified the value of the profile in critical prevention.

摘要

目的

确定不同 COVID-19 患者的抗体和细胞因子谱。

方法

本研究纳入了不同临床分类的 COVID-19 患者。使用 ELISA 检测 IgG 抗体、IgA、IgM、IgE 和针对 N 和 S 蛋白的 IgG 亚类的水平。使用活 SARS-CoV-2 的毒素中和测定法(TNA)测定中和抗体滴度。使用 Protein Sample Ella-Simple ELISA 系统测量 8 种细胞因子(包括 IL-2、IL-4、IL-6、IL-10、CCL2、CXCL10、IFN-γ 和 TNF-α)的浓度。通过 t 检验或 Mann-Whitney 检验比较重症和轻症患者之间的抗体和细胞因子差异。

结果

共纳入 79 例 COVID-19 患者,其中 49 例为轻症患者,30 例为重症患者。与轻症患者相比,重症患者的中和抗体和 IgG-S 抗体滴度明显更高。COVID-19 患者 IgG-N 抗体浓度明显高于 IgG-S 抗体。轻症和重症患者 IgG 亚类抗体分布存在显著差异。抗 S 蛋白 IgG3 的阳性率明显高于抗 N 蛋白 IgG3,而抗 S 蛋白 IgG4 的阳性率明显低于抗 N 蛋白 IgG4。COVID-19 患者的 IL-2 低于健康人,而 COVID-19 患者的 IL-4、IL-6、CCL2、IFN-γ 和 TNF-α均高于健康人。重症患者的 IL-6 明显高于轻症患者。抗 S 蛋白抗体的抗体水平与中和抗体滴度呈正相关,但细胞因子与中和抗体无相关性。

结论

我们的研究结果表明,重症 COVID-19 患者的抗体水平强于轻症患者,细胞因子风暴与 COVID-19 严重程度有关。COVID-19 患者抗 S 蛋白抗体和抗 N 蛋白抗体的免疫球蛋白类型存在差异,并阐明了该谱在重症预防中的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f83/8417126/ca359e2b1d20/fimmu-12-723585-g001.jpg

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