PDF(Pubmed)
Abstract：
OBJECTIVE: Interleukin 6 (IL-6) levels at hospital admission have been suggested for disease prognosis, and IL-6 antagonists have been suggested for the treatment of patients with severe COVID-19. However, less is known about the relationship between pre-COVID-19 IL-6 levels and the risk of severe COVID-19. To fill in this gap, here we extensively investigated the association of genetically instrumented IL-6 pathway components with the risk of severe COVID-19.
METHODS: We used a two-sample Mendelian randomization study design and retrieved genetic instruments for blood biomarkers of IL-6 activation, including IL-6, soluble IL-6 receptor, IL-6 signal transducer, and CRP, from respective large available GWASs. To establish associations of these instruments with COVID-19 outcomes, we used data from the Host Genetics Initiative and GenOMICC studies.
RESULTS: Our analyses revealed inverse associations of genetically instrumented levels of IL-6 and its soluble receptor with the risk of developing severe disease (OR = 0.60 and 0.94, respectively). They also demonstrated a positive association of severe disease with the soluble signal transducer level (OR = 1.13). Only IL-6 associations with severe COVID-19 outcomes reached the significance threshold corrected for multiple testing (p < 0.003; with COVID-19 hospitalization and critical illness).
CONCLUSIONS: These potential causal relationships for pre-COVID-19 IL-6 levels with the risk of developing severe symptoms provide opportunities for further evaluation of these factors as prognostic/preventive markers of severe COVID-19. Further studies will need to clarify whether the higher risk for a severe disease course with lower baseline IL-6 levels may also extend to other infectious diseases.
METHODS: We used a two-sample Mendelian randomization study design and retrieved genetic instruments for blood biomarkers of IL-6 activation, including IL-6, soluble IL-6 receptor, IL-6 signal transducer, and CRP, from respective large available GWASs. To establish associations of these instruments with COVID-19 outcomes, we used data from the Host Genetics Initiative and GenOMICC studies.
RESULTS: Our analyses revealed inverse associations of genetically instrumented levels of IL-6 and its soluble receptor with the risk of developing severe disease (OR = 0.60 and 0.94, respectively). They also demonstrated a positive association of severe disease with the soluble signal transducer level (OR = 1.13). Only IL-6 associations with severe COVID-19 outcomes reached the significance threshold corrected for multiple testing (p < 0.003; with COVID-19 hospitalization and critical illness).
CONCLUSIONS: These potential causal relationships for pre-COVID-19 IL-6 levels with the risk of developing severe symptoms provide opportunities for further evaluation of these factors as prognostic/preventive markers of severe COVID-19. Further studies will need to clarify whether the higher risk for a severe disease course with lower baseline IL-6 levels may also extend to other infectious diseases.
摘要：
目的：入院时的白细胞介素6（IL-6）水平已被认为是疾病预后的指标。和IL-6拮抗剂已被建议用于治疗患有严重COVID-19的患者。然而,对COVID-19前IL-6水平与严重COVID-19风险之间的关系知之甚少。为了填补这个空白，在这里,我们广泛调查了基因工具化的IL-6途径组分与重症COVID-19风险的关联.
方法：我们使用了孟德尔随机双样本研究设计，并检索了IL-6激活的血液生物标志物的遗传仪器，包括IL-6，可溶性IL-6受体，IL-6信号转换器,CRP,从各自的大型可用GWAS。为了建立这些工具与COVID-19结果的关联，我们使用了宿主遗传学倡议和GenOMICC研究的数据.
结果：我们的分析显示，IL-6及其可溶性受体的基因测量水平与发生严重疾病的风险呈负相关（OR分别为0.60和0.94）。他们还证明了严重疾病与可溶性信号转导水平的正相关（OR=1.13）。只有IL-6与严重COVID-19结局的关联达到了多重测试校正的显著性阈值(p<0.003；COVID-19住院和危重疾病)。
结论：COVID-19前IL-6水平与出现严重症状的风险的这些潜在因果关系为进一步评估这些因素作为严重COVID-19的预后/预防标志物提供了机会。进一步的研究将需要澄清具有较低基线IL-6水平的严重疾病过程的较高风险是否也可能扩展到其他传染病。
方法：我们使用了孟德尔随机双样本研究设计，并检索了IL-6激活的血液生物标志物的遗传仪器，包括IL-6，可溶性IL-6受体，IL-6信号转换器,CRP,从各自的大型可用GWAS。为了建立这些工具与COVID-19结果的关联，我们使用了宿主遗传学倡议和GenOMICC研究的数据.
结果：我们的分析显示，IL-6及其可溶性受体的基因测量水平与发生严重疾病的风险呈负相关（OR分别为0.60和0.94）。他们还证明了严重疾病与可溶性信号转导水平的正相关（OR=1.13）。只有IL-6与严重COVID-19结局的关联达到了多重测试校正的显著性阈值(p<0.003；COVID-19住院和危重疾病)。
结论：COVID-19前IL-6水平与出现严重症状的风险的这些潜在因果关系为进一步评估这些因素作为严重COVID-19的预后/预防标志物提供了机会。进一步的研究将需要澄清具有较低基线IL-6水平的严重疾病过程的较高风险是否也可能扩展到其他传染病。
