Background COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19-associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and differentially expressed genes as well as significantly enriched gene sets were identified. Results We enrolled seven COVID19 + (PCR positive, 2 SARS-CoV-2 genes) and seven age- and sex-matched COVID19- (PCR negative) control ICU patients. Cohorts were well-balanced with the exception that COVID19− patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19 + patients were more likely to suffer bilateral pneumonia. The mortality rate for this cohort of COVID19 + ICU patients was 29%. As indicated by both single-gene based and gene set (GSEA) approaches, the major disease-specific transcriptional responses of leukocytes in critically ill COVID19 + ICU patients were: (i) a robust overrepresentation of interferon-related gene expression; (ii) a marked decrease in the transcriptional level of genes contributing to general protein synthesis and bioenergy metabolism; and (iii) the dysregulated expression of genes associated with coagulation, platelet function, complement activation, and tumour necrosis factor/interleukin 6 signalling. Conclusions Our findings demonstrate that critically ill COVID19 + patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19− patients, providing guidance for future targeted studies exploring novel prognostic and therapeutic aspects of COVID19.

中文翻译：

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重症 COVID19 患者白细胞的转录分析：对干扰素反应和凝血的影响

背景 COVID19 是由 SARS-CoV-2 病毒引起的，并与导致器官功能障碍和死亡的严重炎症有关。我们的目的是比较 COVID19 阳性重症患者的白细胞转录组与 COVID19 阴性患者的白细胞转录组，以更好地了解 COVID19 相关宿主反应。在这些研究中，所有入住我们三级护理重症监护病房 (ICU) 的疑似感染 SARS-CoV-2 的患者都使用标准化的医院筛查方法，在入住 ICU 时采集了血液样本。然后通过核糖核酸测序 (RNAseq) 对白细胞进行转录组分析，并鉴定出差异表达的基因以及显着富集的基因集。结果 我们招募了 7 个 COVID19+（PCR 阳性，2 个 SARS-CoV-2 基因）和 7 个年龄和性别匹配的 COVID19-（PCR 阴性）对照 ICU 患者。除了 COVID19− 患者的总白细胞计数和循环中性粒细胞显着更高，并且 COVID19+ 患者更容易患双侧肺炎之外，队列平衡良好。这组 COVID19 + ICU 患者的死亡率为 29%。正如基于单基因和基因集（GSEA）方法所表明的，重症 COVID19 + ICU 患者中白细胞的主要疾病特异性转录反应是：（i）干扰素相关基因表达的强烈过度表达；(ii) 有助于一般蛋白质合成和生物能量代谢的基因转录水平显着降低；(iii) 与凝血相关的基因表达失调，血小板功能、补体激活和肿瘤坏死因子/白细胞介素 6 信号传导。结论我们的研究结果表明，重症 COVID19+ 患者在入住 ICU 的第 1 天显示出独特的白细胞转录谱，将他们与 COVID19− 患者区分开来，为未来探索 COVID19 新预后和治疗方面的靶向研究提供指导。