The current pandemic of coronavirus disease 19 (COVID-19) has affected millions of individuals and caused thousands of deaths worldwide. The pathophysiology of the disease is complex and mostly unknown. Therefore, identifying the molecular mechanisms that promote progression of the disease is critical to overcome this pandemic. To address such issues, recent studies have reported transcriptomic profiles of cells, tissues and fluids from COVID-19 patients that mainly demonstrated activation of humoral immunity, dysregulated type I and III interferon expression, intense innate immune responses and inflammatory signaling. Here, we provide novel perspectives on the pathophysiology of COVID-19 using robust functional approaches to analyze public transcriptome datasets. In addition, we compared the transcriptional signature of COVID-19 patients with individuals infected with SARS-CoV-1 and Influenza A (IAV) viruses. We identified a core transcriptional signature induced by the respiratory viruses in peripheral leukocytes, whereas the absence of significant type I interferon/antiviral responses characterized SARS-CoV-2 infection. We also identified the higher expression of genes involved in metabolic pathways including heme biosynthesis, oxidative phosphorylation and tryptophan metabolism. A BTM-driven meta-analysis of bronchoalveolar lavage fluid (BALF) from COVID-19 patients showed significant enrichment for neutrophils and chemokines, which were also significant in data from lung tissue of one deceased COVID-19 patient. Importantly, our results indicate higher expression of genes related to oxidative phosphorylation both in peripheral mononuclear leukocytes and BALF, suggesting a critical role for mitochondrial activity during SARS-CoV-2 infection. Collectively, these data point for immunopathological features and targets that can be therapeutically exploited to control COVID-19.

当前冠状病毒病 19 (COVID-19) 的大流行已影响了全球数百万人，并导致数千人死亡。该疾病的病理生理学很复杂，而且大多是未知的。因此，确定促进疾病进展的分子机制对于克服这一流行病至关重要。为了解决这些问题，最近的研究报告了 COVID-19 患者的细胞、组织和体液的转录组学特征，主要证明了体液免疫的激活、I 型和 III 型干扰素表达失调、强烈的先天免疫反应和炎症信号传导。在这里，我们使用强大的功能方法来分析公共转录组数据集，为 COVID-19 的病理生理学提供了新颖的视角。此外，我们还比较了 COVID-19 患者与感染 SARS-CoV-1 和甲型流感 (IAV) 病毒的个体的转录特征。我们在外周白细胞中发现了由呼吸道病毒诱导的核心转录特征，而缺乏显着的 I 型干扰素/抗病毒反应是 SARS-CoV-2 感染的特征。我们还发现了参与代谢途径（包括血红素生物合成、氧化磷酸化和色氨酸代谢）的基因的较高表达。由 BTM 驱动的对 COVID-19 患者支气管肺泡灌洗液 (BALF) 的荟萃分析显示，中性粒细胞和趋化因子显着富集，这在一名已故 COVID-19 患者肺组织的数据中也很重要。重要的是，我们的结果表明，外周单核白细胞和 BALF 中与氧化磷酸化相关的基因表达较高，这表明线粒体活性在 SARS-CoV-2 感染期间发挥着关键作用。 总的来说，这些数据表明了可用于控制 COVID-19 的免疫病理学特征和靶点。