The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide and with notable heterogeneity in its clinical presentation. Probability of contracting this highly contagious infection is similar across age groups but disease severity and fatality among aged patients with or without comorbidities are reportedly higher. Previous studies suggest that age associated transcriptional changes in lung and immune system results in a proinflammatory state and increased susceptibility to infectious lung diseases. Similarly, SARS-CoV-2 infection could augment ageing-related gene expression alterations resulting in severe outcomes in elderly patients. To identify genes that can potentially increase covid-19 disease severity in ageing people, we compared age associated gene expression changes with disease-associated expression changes in lung/BALF and whole blood obtained from publicly available data. We observed (i) a significant overlap of gene expression profiles of patients’ BALF and blood with lung and blood of the healthy group, respectively; (ii) a more pronounced overlap in blood compared to lung; and (iii) a similar overlap between host genes interacting with SARS-CoV-2 and ageing blood transcriptome. Pathway enrichment analysis of overlapping gene sets suggest that infection alters expression of genes already dysregulated in the elderly, which together may lead to poor prognosis. eQTLs in these genes may also confer poor outcome in young patients worsening with age and comorbidities. Further, the pronounced overlap observed in blood may explain clinical symptoms including blood clots, strokes, heart attack, multi-organ failure etc. in severe cases. This model based on a limited patient dataset seems robust and holds promise for testing larger tissue specific datasets from patients with varied severity and across populations.

中文翻译：

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SARS-CoV-2感染引起的与年龄相关的基因表达改变导致老年人预后不良

由严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 引起的持续大流行已经影响了全球数百万人，并且其临床表现具有显着的异质性。不同年龄组感染这种高度传染性感染的可能性相似，但据报道，有或没有合并症的老年患者的疾病严重程度和死亡率更高。先前的研究表明，与年龄相关的肺和免疫系统的转录变化会导致促炎状态并增加对传染性肺病的易感性。同样，SARS-CoV-2 感染可能会增加与衰老相关的基因表达改变，从而导致老年患者出现严重后果。为了确定可能增加老年人 COVID-19 疾病严重程度的基因，我们将年龄相关的基因表达变化与从公开数据中获得的肺/BALF 和全血中疾病相关的表达变化进行了比较。我们观察到 (i) 患者 BALF 和血液的基因表达谱分别与健康组的肺和血液有显着重叠；(ii) 与肺相比，血液中有更明显的重叠；(iii) 与 SARS-CoV-2 相互作用的宿主基因与老化的血液转录组之间存在类似的重叠。重叠基因集的通路富集分析表明，感染改变了老年人中已经失调的基因的表达，这可能共同导致预后不良。这些基因中的 eQTL 也可能导致随着年龄和合并症恶化的年轻患者的预后不佳。更多，在血液中观察到的明显重叠可以解释临床症状，包括严重病例中的血栓、中风、心脏病发作、多器官衰竭等。这种基于有限患者数据集的模型似乎很稳健，并有望测试来自不同严重程度和不同人群的患者的更大组织特定数据集。