Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population.
Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population.
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DOI：
10.7554/elife.63033
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发表时间：
2021-05-04
期刊：
影响因子：
7.7
通讯作者：
Nightingale Health UK Biobank Initiative
中科院分区：
文献类型：
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作者：
Julkunen H;Cichońska A;Slagboom PE;Würtz P;Nightingale Health UK Biobank Initiative
低级别炎症的生物标志物与严重感染性疾病病程的易感性相关，即使在发病前测量也是如此。我们研究了核磁共振（NMR）光谱测量的代谢生物标志物是否与来自UK Biobank的105,146名一般健康个体对严重肺炎（2507例住院或死亡病例）和严重COVID-19（652例住院病例）的易感性相关，这些个体的血液样本收集于2007-2010年。代谢生物标志物关联的总体特征与严重肺炎和严重COVID-19的风险相似。由25种蛋白质、脂肪酸、氨基酸和脂质组成的多生物标志物评分与严重COVID-19易感性增加（最高五分位数与最低五分位数的比值比为2.9 [95%CI 2.1-3.8]）和血液采样后7-11年发生的严重肺炎事件（2.6[1.7-3.9]）同样强烈相关。然而，多生物标志物评分水平升高的人群在采血后头2年内发生严重肺炎的风险是长期风险的4倍多（8.0[4.1-15.6]）。如果这些关于血液采样后最初几年对严重肺炎易感性增加的假设发现延伸到严重的COVID-19，代谢生物标志物分析可能会补充现有的识别高风险个体的工具。这些结果为代谢生物标志物如何反映普通人群对COVID-19严重感染和其他感染的易感性提供了新的分子理解。缓解COVID-19大流行的国家政策包括对被认为有严重和潜在致命病例高风险的人采取更严格的措施。虽然年龄较大和已有的健康状况是很强的风险因素，但人们对人群中易感性差异如此之大的原因知之甚少。患有心脏代谢疾病（如糖尿病和肝病）或慢性炎症的人患严重COVID-19和肺炎等其他感染的风险更高。这些情况改变了血液中循环的分子，提供了潜在的“生物标志物”，以确定一个人是否更有可能患上致命的感染。发现这些血液生物标志物可以帮助识别那些即使没有被诊断出患有心脏代谢疾病也容易受到威胁生命的感染的人。为了找到这些生物标志物，Julkunen等人研究了十多年前从英国105,000名健康个体收集的血液样本。数据显示，具有与低度炎症和心脏代谢疾病相关的生物标志物的个体更有可能因肺炎而死亡或住院。基于其中25个生物标志物的评分提供了严重肺炎的最佳预测指标。与预测十年后的肺炎病例相比，这种生物标志物评分在血液采样后的头几年里的表现要好上四倍。同样的血液生物标志物变化也与采集血液样本十年后发生严重的COVID-19有关。生物标志物评分对重症COVID-19和重症肺炎长期风险的预测价值相似。Julkunen等人提出，代谢生物标志物反映了抑制免疫，从而损害了对感染的反应。来自10多万人的结果表明，这些血液生物标志物可能有助于识别患有严重COVID-19或其他传染病的高风险人群。
Biomarkers of low-grade inflammation have been associated with susceptibility to a severe infectious disease course, even when measured prior to disease onset. We investigated whether metabolic biomarkers measured by nuclear magnetic resonance (NMR) spectroscopy could be associated with susceptibility to severe pneumonia (2507 hospitalised or fatal cases) and severe COVID-19 (652 hospitalised cases) in 105,146 generally healthy individuals from UK Biobank, with blood samples collected 2007–2010. The overall signature of metabolic biomarker associations was similar for the risk of severe pneumonia and severe COVID-19. A multi-biomarker score, comprised of 25 proteins, fatty acids, amino acids, and lipids, was associated equally strongly with enhanced susceptibility to severe COVID-19 (odds ratio 2.9 [95%CI 2.1–3.8] for highest vs lowest quintile) and severe pneumonia events occurring 7–11 years after blood sampling (2.6 [1.7–3.9]). However, the risk for severe pneumonia occurring during the first 2 years after blood sampling for people with elevated levels of the multi-biomarker score was over four times higher than for long-term risk (8.0 [4.1–15.6]). If these hypothesis generating findings on increased susceptibility to severe pneumonia during the first few years after blood sampling extend to severe COVID-19, metabolic biomarker profiling could potentially complement existing tools for identifying individuals at high risk. These results provide novel molecular understanding on how metabolic biomarkers reflect the susceptibility to severe COVID-19 and other infections in the general population. National policies for mitigating the COVID-19 pandemic include stricter measures for people considered to be at high risk of severe and potentially fatal cases of the disease. Although older age and pre-existing health conditions are strong risk factors, it is poorly understood why susceptibility varies so widely in the population. People with cardiometabolic diseases, such as diabetes and liver diseases, or chronic inflammation are at higher risk of severe COVID-19 and other infections including pneumonia. These conditions alter the molecules circulating in the blood, providing potential ‘biomarkers’ to determine whether a person is more likely to develop a fatal infection. Uncovering these blood biomarkers could help to identify people who are prone to life-threatening infections despite not having ever been diagnosed with a cardiometabolic disease. To find these biomarkers, Julkunen et al. studied blood samples that had been collected from 105,000 healthy individuals in the United Kingdom over ten years ago. The data showed that individuals with biomarkers linked to low-grade inflammation and cardiometabolic disease were more likely to have died or been hospitalised with pneumonia. A score based on 25 of these biomarkers provided the best predictor of severe pneumonia. This biomarker score performed up to four times better within the first few years after blood sampling compared to predicting cases of pneumonia a decade later. The same blood biomarker changes were also linked with developing severe COVID-19 over ten years after the blood samples had been collected. The predictive value of the biomarker score was similar for both severe COVID-19 and the long-term risk of severe pneumonia. Julkunen et al. propose that the metabolic biomarkers reflect inhibited immunity that impairs response to infections. The results from over 100,000 individuals suggest that these blood biomarkers may help to identify people at high risk of severe COVID-19 or other infectious diseases.