Potent SARS-CoV-2-Specific T Cell Immunity and Low Anaphylatoxin Levels Correlate With Mild Disease Progression in COVID-19 Patients.
Potent SARS-CoV-2-Specific T Cell Immunity and Low Anaphylatoxin Levels Correlate With Mild Disease Progression in COVID-19 Patients.
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DOI：
10.3389/fimmu.2021.684014
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发表时间：
2021
影响因子：
7.3
通讯作者：
Posch W
中科院分区：
文献类型：
--
作者：
Lafon E;Diem G;Witting C;Zaderer V;Bellmann-Weiler RM;Reindl M;Bauer A;Griesmacher A;Fux V;Hoermann G;Miller C;Zabernigg A;Wöll E;Wilflingseder D;Lass-Flörl C;Posch W
T细胞在许多呼吸系统病毒感染的早期控制和清除中起着基础性作用。在SARS-CoV-2感染者中，CD_4~+和CD_8~+T细胞急剧减少的淋巴细胞减少与冠状病毒病2019(新冠肺炎)相关的疾病严重程度和死亡率相关。在这项研究中，我们描述了轻度、重度和危重新冠肺炎患者诱导的细胞和体液免疫反应。对37例轻、重、危重新冠肺炎患者和10例健康体检者外周血单个核细胞在完全免疫优势型γ-CoV-2基质、核衣壳蛋白和刺突蛋白的多肽池刺激下，用干扰素-SARS ELISpot和多色流式细胞仪进行分析。此外，通过各种商用的ELISA平台对SARS-CoV-2抗体水平、中和能力和过敏毒素水平进行了评估。我们的数据清楚地表明，与重症或重症新冠肺炎患者相比，轻度新冠肺炎患者对SARS-CoV-2特异性CD8+T细胞的诱导明显增强，干扰素γ的产生也更高。在所有患者中都检测到具有相似中和活性的SARS-CoV-2特异性抗体，但危重患者的总免疫球蛋白滴度最高。最后，在重症和危重新冠肺炎患者中发现了过敏毒素C3a和C5a水平升高，这可能是由于这些患者中抗体效价升高导致免疫复合物形成异常所致。至关重要的是，我们提供了新冠肺炎患者细胞和体液免疫反应的全貌，并证明强大的多功能CD8+T细胞反应伴随着低过敏毒素水平与轻度感染相关。此外，我们的数据表明，高滴度的SARS-CoV-2抗体与严重的疾病进展有关。
T cells play a fundamental role in the early control and clearance of many viral infections of the respiratory system. In SARS-CoV-2-infected individuals, lymphopenia with drastically reduced CD4+ and CD8+ T cells correlates with Coronavirus disease 2019 (COVID-19)-associated disease severity and mortality. In this study, we characterized cellular and humoral immune responses induced in patients with mild, severe and critical COVID-19. Peripheral blood mononuclear cells of 37 patients with mild, severe and critical COVID-19 and 10 healthy individuals were analyzed by IFNγ ELISpot and multi-color flow cytometry upon stimulation with peptide pools covering complete immunodominant SARS-CoV-2 matrix, nucleocapsid and spike proteins. In addition SARS-CoV-2 antibody levels, neutralization abilities and anaphylatoxin levels were evaluated by various commercially available ELISA platforms. Our data clearly demonstrates a significantly stronger induction of SARS-CoV-2 specific CD8+ T lymphocytes and higher IFNγ production in patients with mild compared to patients with severe or critical COVID-19. In all patients SARS-CoV-2-specific antibodies with similar neutralizing activity were detected, but highest titers of total IgGs were observed in critical patients. Finally, elevated anaphylatoxin C3a and C5a levels were identified in severe and critical COVID-19 patients probably caused by aberrant immune complex formation due to elevated antibody titers in these patients. Crucially, we provide a full picture of cellular and humoral immune responses of COVID-19 patients and prove that robust polyfunctional CD8+ T cell responses concomitant with low anaphylatoxin levels correlate with mild infections. In addition, our data indicates that high SARS-CoV-2 antibody titers are associated with severe disease progression.
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影响因子：
12.8
作者：
Cugno M;Meroni PL;Gualtierotti R;Griffini S;Grovetti E;Torri A;Lonati P;Grossi C;Borghi MO;Novembrino C;Boscolo M;Uceda Renteria SC;Valenti L;Lamorte G;Manunta M;Prati D;Pesenti A;Blasi F;Costantino G;Gori A;Bandera A;Tedesco F;Peyvandi F
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影响因子：
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影响因子：
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