Severe Adaptive Immune Suppression May Be Why Patients With Severe COVID-19 Cannot Be Discharged From the ICU Even After Negative Viral Tests.
Severe Adaptive Immune Suppression May Be Why Patients With Severe COVID-19 Cannot Be Discharged From the ICU Even After Negative Viral Tests.
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DOI：
10.3389/fimmu.2021.755579
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发表时间：
2021
影响因子：
7.3
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Zhou Y;Liao X;Song X;He M;Xiao F;Jin X;Xie X;Zhang Z;Wang B;Zhou C;Kang Y;Zhang W
在COVID-19疫情期间，出现了一些重症患者病情危重，即使病毒检测呈阴性也无法从ICU出院的现象。为了探索潜在的机制，我们收集了这些患者的血液样本，并分析了外周免疫细胞的基因表达谱。我们发现，所有入组患者，无论与不同症状和炎症反应相关的基因是否发生变化，均表现出普遍和严重的适应性免疫相关基因表达降低，尤其是与T/B细胞臂和HLA分子相关的基因，并且这些患者表现出长期继发感染。此外，经典免疫抑制分子PD-1、PD-L1和CTLA-4的表达未发现显著变化，表明适应性免疫抑制可能不是由于这些基因的变化。根据已发表的文献和我们的数据，这种适应性免疫抑制很可能是由对严重感染的“失调的宿主反应”引起的，类似于其他严重感染的脓毒症患者中存在的免疫抑制。
During the COVID-19 pandemic, a phenomenon emerged in which some patients with severe disease were critically ill and could not be discharged from the ICU even though they exhibited negative viral tests. To explore the underlying mechanism, we collected blood samples from these patients and analyzed the gene expression profiles of peripheral immune cells. We found that all enrolled patients, regardless of changes in genes related to different symptoms and inflammatory responses, showed universally and severely decreased expression of adaptive immunity-related genes, especially those related to T/B cell arms and HLA molecules, and that these patients exhibited long-term secondary infections. In addition, no significant change was found in the expression of classic immunosuppression molecules including PD-1, PD-L1, and CTLA-4, suggesting that the adaptive immune suppression may not be due to the change of these genes. According to the published literatures and our data, this adaptive immunosuppression is likely to be caused by the “dysregulated host response” to severe infection, similar to the immunosuppression that exists in other severely infected patients with sepsis.