SARS-CoV-2-Induced ARDS Associates with MDSC Expansion, Lymphocyte Dysfunction, and Arginine Shortage.
SARS-CoV-2-Induced ARDS Associates with MDSC Expansion, Lymphocyte Dysfunction, and Arginine Shortage.
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DOI：
10.1007/s10875-020-00920-5
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发表时间：
2021-04
影响因子：
9.1
通讯作者：
Tadié JM
中科院分区：
文献类型：
--
作者：
Reizine F;Lesouhaitier M;Gregoire M;Pinceaux K;Gacouin A;Maamar A;Painvin B;Camus C;Le Tulzo Y;Tattevin P;Revest M;Le Bot A;Ballerie A;Cador-Rousseau B;Lederlin M;Lebouvier T;Launey Y;Latour M;Verdy C;Rossille D;Le Gallou S;Dulong J;Moreau C;Bendavid C;Roussel M;Cogne M;Tarte K;Tadié JM
SARS-CoV-2感染可导致严重急性呼吸窘迫综合征(ARDS)，机械通气时间延长，死亡率高。有趣的是，新冠肺炎相关性急性呼吸窘迫综合征与败血症相关的免疫抑制具有共同的生物学和临床特征，因为淋巴细胞减少和与晚期死亡相关的获得性感染是常见的。需要探索新冠肺炎相关性淋巴细胞减少症的机制，因为它们可能导致重症监护病房(ICU)患者病毒清除延迟和死亡率增加。对26例具有临床特征的新冠肺炎患者在入院后0、4和7天进行了彻底的表型和功能调查。我们发现，在两组人口统计学参数和病史没有任何差异的情况下，与新冠肺炎中度肺炎住院患者相比，ARDS患者的髓系抑制细胞(MDSC)数量增加，CD8pos效应记忆细胞数量减少。有趣的是，新冠肺炎相关的骨髓间充质干细胞的扩张与淋巴细胞减少和精氨酸酶活性增强直接相关。最后，新冠肺炎患者的T细胞体外增殖能力显著降低，补充精氨酸可以恢复。本研究报告了多药耐药干细胞在新冠肺炎相关急性呼吸窘迫综合征中的关键作用。我们的发现为这些ICU患者提供了补充精氨酸作为辅助治疗的可能性，旨在减少免疫抑制并帮助病毒清除，从而减少机械通气时间、医院感染获得和死亡率。网上版载有补充材料，可在10.1007/s10875-020-00920-5查阅。
The SARS-CoV-2 infection can lead to a severe acute respiratory distress syndrome (ARDS) with prolonged mechanical ventilation and high mortality rate. Interestingly, COVID-19-associated ARDS share biological and clinical features with sepsis-associated immunosuppression since lymphopenia and acquired infections associated with late mortality are frequently encountered. Mechanisms responsible for COVID-19-associated lymphopenia need to be explored since they could be responsible for delayed virus clearance and increased mortality rate among intensive care unit (ICU) patients. A series of 26 clinically annotated COVID-19 patients were analyzed by thorough phenotypic and functional investigations at days 0, 4, and 7 after ICU admission. We revealed that, in the absence of any difference in demographic parameters nor medical history between the two groups, ARDS patients presented with an increased number of myeloid-derived suppressor cells (MDSC) and a decreased number of CD8pos effector memory cell compared to patients hospitalized for COVID-19 moderate pneumonia. Interestingly, COVID-19-related MDSC expansion was directly correlated to lymphopenia and enhanced arginase activity. Lastly, T cell proliferative capacity in vitro was significantly reduced among COVID-19 patients and could be restored through arginine supplementation. The present study reports a critical role for MDSC in COVID-19-associated ARDS. Our findings open the possibility of arginine supplementation as an adjuvant therapy for these ICU patients, aiming to reduce immunosuppression and help virus clearance, thereby decreasing the duration of mechanical ventilation, nosocomial infection acquisition, and mortality. The online version contains supplementary material available at 10.1007/s10875-020-00920-5.
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