Genetic risk for severe COVID-19 correlates with lower inflammatory marker levels in a SARS-CoV-2-negative cohort.
Genetic risk for severe COVID-19 correlates with lower inflammatory marker levels in a SARS-CoV-2-negative cohort.
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在SARS-COV-2阴性队列中，严重COVID-19的遗传风险与较低的炎症标记水平相关。
DOI：
10.1002/cti2.1292
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发表时间：
2021
影响因子：
5.8
通讯作者：
Nixon DF
中科院分区：
文献类型：
--
作者：
Powell TR;Hotopf M;Hatch SL;Breen G;Duarte RRR;Nixon DF
在严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染和细胞因子风暴爆发之前，2019 年冠状病毒病 (COVID-19) 易感个体的炎症标志物水平有何不同仍不清楚。我们使用遗传风险评分来模拟对严重 COVID-19 的易感性与 35 种炎症标志物的基线水平的相关性，并测试它们在 SARS-CoV-2 阴性人群队列中的影响。由于年龄和体重指数对严重 COVID-19 风险的影响已确定，我们进一步考虑了这些变量如何与遗传风险相互作用以影响炎症标志物水平。作为英国人口研究的一部分，我们获取了 406 名 SARS-CoV-2 阴性个体的数据。采用多重电化学发光方法检测血清，并检测了 35 种炎症标志物。相应的基因型数据以及针对严重 COVID-19 的大型全基因组关联研究的结果使我们能够构建遗传风险评分并测试其对炎症蛋白水平的影响。我们的结果显示，重症 COVID-19 的遗传风险较高与血液中干扰素 γ (IFN-γ)、血管内皮生长因子 D (VEGF-D) 和肿瘤坏死因子 α (TNF-α) 水平较低有关。具有高遗传风险的人的炎症特征与年龄和肥胖相关的正常情况越来越不同。我们的结果支持这样的理论，即面临严重 COVID-19 风险的个体先天免疫缺陷，其特征是基线时炎症标志物水平降低，包括 IFN-γ、VEGF-D 和 TNF-α。我们假设继发性过度活跃的适应性免疫反应可能随后解释了在 SARS-CoV-2 阳性 COVID-19 患者中观察到的高水平细胞因子。我们使用遗传风险评分来模拟对严重 COVID-19 的易感性与 35 种炎症标志物的基线水平的相关性，并测试它们在 SARS-CoV-2 阴性人群队列中的影响。重症 COVID-19 的遗传风险较高与血液中干扰素 γ (IFN-γ)、血管内皮生长因子 D (VEGF-D) 和肿瘤坏死因子 α (TNF-α) 水平较低有关。具有高遗传风险的人的炎症特征与年龄和肥胖相关的正常情况越来越不同。
It remains unknown how inflammatory marker levels differ amongst individuals susceptible to coronavirus disease 2019 (COVID‐19), prior to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and the onset of the cytokine storm. We used genetic risk scores to model how susceptibility to severe COVID‐19 correlates with baseline levels of 35 inflammatory markers, by testing their impact in a SARS‐CoV‐2‐negative population cohort. Because of the established effects of age and body mass index on severe COVID‐19 risk, we further considered how these variables interacted with genetic risk to affect inflammatory marker levels. We accessed data on 406 SARS‐CoV‐2‐negative individuals as part of a UK population study. Multiplex electrochemiluminescence methods were applied to blood serum, and 35 inflammatory markers were assayed. Corresponding genotype data, alongside results from a large genome‐wide association study of severe COVID‐19, allowed us to construct genetic risk scores and to test their impact on inflammatory protein levels. Our results revealed that a higher genetic risk for severe COVID‐19 was associated with lower blood levels of interferon gamma (IFN‐γ), vascular endothelial growth factor D (VEGF‐D) and tumor necrosis factor alpha (TNF‐α). Inflammatory profiles of those with high genetic risk increasingly diverge from the norm in association with age and obesity. Our results support the theory that individuals at risk of severe COVID‐19 have a deficient innate immunity marked by reduced levels of inflammatory markers at baseline, including IFN‐γ, VEGF‐D and TNF‐α. We hypothesise that a secondary overactive adaptive immune response may subsequently explain the high levels of cytokines observed in SARS‐CoV‐2‐positive COVID‐19 patients. We used genetic risk scores to model how susceptibility to severe COVID‐19 correlates with baseline levels of 35 inflammatory markers, by testing their impact in a SARS‐CoV‐2‐negative population cohort. Higher genetic risk for severe COVID‐19 was associated with lower blood levels of interferon gamma (IFN‐γ), vascular endothelial growth factor D (VEGF‐D) and tumor necrosis factor alpha (TNF‐α). Inflammatory profiles of those with high genetic risk increasingly diverge from the norm in association with age and obesity.
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影响因子：
5
作者：
Gadotti AC;de Castro Deus M;Telles JP;Wind R;Goes M;Garcia Charello Ossoski R;de Padua AM;de Noronha L;Moreno-Amaral A;Baena CP;Tuon FF
通讯作者：
Tuon FF
影响因子：
9.2
作者：
Choi, Shing Wan;O'Reilly, Paul F.
通讯作者：
O'Reilly, Paul F.
影响因子：
82.9
作者：
Del Valle DM;Kim-Schulze S;Huang HH;Beckmann ND;Nirenberg S;Wang B;Lavin Y;Swartz TH;Madduri D;Stock A;Marron TU;Xie H;Patel M;Tuballes K;Van Oekelen O;Rahman A;Kovatch P;Aberg JA;Schadt E;Jagannath S;Mazumdar M;Charney AW;Firpo-Betancourt A;Mendu DR;Jhang J;Reich D;Sigel K;Cordon-Cardo C;Feldmann M;Parekh S;Merad M;Gnjatic S
通讯作者：
Gnjatic S
影响因子：
15.1
作者：
Shah, Sachin J.;Barish, Peter N.;Langelier, Charles
通讯作者：
Langelier, Charles
影响因子：
6.6
作者：
Palmos, Alish B.;Chung, Raymond;Powell, Timothy R.
通讯作者：
Powell, Timothy R.