Uncontrolled Innate and Impaired Adaptive Immune Responses in Patients with COVID-19 Acute Respiratory Distress Syndrome.
Uncontrolled Innate and Impaired Adaptive Immune Responses in Patients with COVID-19 Acute Respiratory Distress Syndrome.
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DOI：
10.1164/rccm.202005-1885oc
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发表时间：
2020-12-01
影响因子：
24.7
通讯作者：
de Prost N
中科院分区：
文献类型：
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作者：
Hue S;Beldi-Ferchiou A;Bendib I;Surenaud M;Fourati S;Frapard T;Rivoal S;Razazi K;Carteaux G;Delfau-Larue MH;Mekontso-Dessap A;Audureau E;de Prost N
基本原理：不受控制的先天性炎症反应和受损的适应性免疫反应与冠状病毒病（COVID-19）患者的临床严重程度相关。目的：比较COVID-19急性呼吸窘迫综合征（ARDS）与非COVID-19 ARDS的免疫病理学，并确定与COVID-19 ARDS患者死亡率相关的生物标志物。方法：前瞻性观察性单中心研究。纳入了2020年3月8日至3月30日期间确诊为RT-PCR证实的严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染和ARDS的免疫功能正常的患者，并与非COVID-19 ARDS患者进行了比较。研究的主要临床终点是第28天的死亡率。在ICU入院的第1-2天和第4-6天进行流式细胞术分析和血清细胞因子测量。测量和主要结果：与非COVID-19 ARDS患者（n = 36）相比，COVID-19患者（n = 38）在年龄、性别和序贯器官衰竭评估和简化急性生理学评分II评分方面无显著差异，但第28天死亡率较高（34% vs. 11%，P = 0.030）。COVID-19患者表现出严重和持续的T CD 4 +（P = 0.002），CD8+（P < 0.0001），和B（P < 0.0001）淋巴细胞减少，单核细胞HLA-DR表达增高EGF（上皮生长因子）、GM-CSF、IL-10、CCL 2/MCP-1、CCL 3/MIP-1a、CXCL 10/IP-10、CCL 5/RANTES和CCL 20/MIP-3a的血清浓度升高（P < 0.001）。在调整年龄和序贯器官衰竭评估后，在第28天死亡的COVID-19患者中，血清CXCL 10/IP-10（P = 0.047）和GM-CSF（P = 0.050）较高，鼻咽RT-PCR循环阈值较低（P = 0.010）。结论：在COVID-19 ARDS中观察到严重的全身淋巴细胞减少和“趋化因子特征”。血清CXCL 10/IP-10和GM-CSF浓度升高以及鼻咽SARS-CoV-2病毒载量升高与第28天死亡率相关。
Rationale: Uncontrolled inflammatory innate response and impaired adaptive immune response are associated with clinical severity in patients with coronavirus disease (COVID-19). Objectives: To compare the immunopathology of COVID-19 acute respiratory distress syndrome (ARDS) with that of non–COVID-19 ARDS, and to identify biomarkers associated with mortality in patients with COVID-19 ARDS. Methods: Prospective observational monocenter study. Immunocompetent patients diagnosed with RT-PCR–confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and ARDS admitted between March 8 and March 30, 2020, were included and compared with patients with non–COVID-19 ARDS. The primary clinical endpoint of the study was mortality at Day 28. Flow cytometry analyses and serum cytokine measurements were performed at Days 1–2 and 4–6 of ICU admission. Measurements and Main Results: As compared with patients with non–COVID-19 ARDS (n = 36), those with COVID-19 (n = 38) were not significantly different regarding age, sex, and Sequential Organ Failure Assessment and Simplified Acute Physiology Score II scores but exhibited a higher Day-28 mortality (34% vs. 11%, P = 0.030). Patients with COVID-19 showed profound and sustained T CD4+ (P = 0.002), CD8+ (P < 0.0001), and B (P < 0.0001) lymphopenia, higher HLA-DR expression on monocytes (P < 0.001) and higher serum concentrations of EGF (epithelial growth factor), GM-CSF, IL-10, CCL2/MCP-1, CCL3/MIP-1a, CXCL10/IP-10, CCL5/RANTES, and CCL20/MIP-3a. After adjusting on age and Sequential Organ Failure Assessment, serum CXCL10/IP-10 (P = 0.047) and GM-CSF (P = 0.050) were higher and nasopharyngeal RT-PCR cycle threshold values lower (P = 0.010) in patients with COVID-19 who were dead at Day 28. Conclusions: Profound global lymphopenia and a “chemokine signature” were observed in COVID-19 ARDS. Increased serum concentrations of CXCL10/IP-10 and GM-CSF, together with higher nasopharyngeal SARS-CoV-2 viral load, were associated with Day-28 mortality.