Laboratory on Thymus Research, Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil.
National Institute for Science and Technology on Neuroimmunomodulation (INCT/NIM), Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil.
Microbiome. 2022 Apr 22;10(1):65. doi: 10.1186/s40168-022-01260-9.
Critically ill 2019 coronavirus disease (COVID-19) patients under invasive mechanical ventilation (IMV) are 10 to 40 times more likely to die than the general population. Although progression from mild to severe COVID-19 has been associated with hypoxia, uncontrolled inflammation, and coagulopathy, the mechanisms involved in the progression to severity are poorly understood.
The virome of tracheal aspirates (TA) from 25 COVID-19 patients under IMV was assessed through unbiased RNA sequencing (RNA-seq), and correlation analyses were conducted using available clinical data. Unbiased sequences from nasopharyngeal swabs (NS) from mild cases and TA from non-COVID patients were included in our study for further comparisons.
We found higher levels and differential expression of human endogenous retrovirus K (HERV-K) genes in TA from critically ill and deceased patients when comparing nasopharyngeal swabs from mild cases to TA from non-COVID patients. In critically ill patients, higher HERV-K levels were associated with early mortality (within 14 days of diagnosis) in the intensive care unit. Increased HERV-K expression in deceased patients was associated with IL-17-related inflammation, monocyte activation, and an increased consumption of clotting/fibrinolysis factors. Moreover, increased HERV-K expression was detected in human primary monocytes from healthy donors after experimental SARS-CoV-2 infection in vitro.
Our data implicate the levels of HERV-K transcripts in the physiopathology of COVID-19 in the respiratory tract of patients under invasive mechanical ventilation. Video abstract.
接受有创机械通气（IMV）治疗的 2019 年冠状病毒病（COVID-19）危重症患者的死亡率比一般人群高 10 至 40 倍。虽然从轻度到重度 COVID-19 的进展与缺氧、失控的炎症和凝血障碍有关，但对导致病情加重的机制仍了解甚少。
通过无偏 RNA 测序（RNA-seq）评估 25 例接受 IMV 治疗的 COVID-19 患者的气管抽吸物（TA）中的病毒组，并使用现有临床数据进行相关分析。我们将轻度病例的鼻咽拭子（NS）和非 COVID 患者的 TA 的无偏序列纳入研究，以进行进一步比较。
与轻度病例的 NS 相比，我们发现重症和死亡患者的 TA 中人类内源性逆转录病毒 K（HERV-K）基因的水平更高且表达差异更大。在危重症患者中，HERV-K 水平升高与 ICU 内早期死亡（诊断后 14 天内）相关。死亡患者的 HERV-K 表达增加与 IL-17 相关炎症、单核细胞激活以及凝血/纤溶因子消耗增加有关。此外，在体外实验性 SARS-CoV-2 感染后，从健康供体的人原代单核细胞中检测到 HERV-K 表达增加。
我们的数据提示，HERV-K 转录本水平与接受有创机械通气的 COVID-19 患者呼吸道的病理生理学有关。视频摘要。
