PDF(Pubmed)
Abstract：
The relationships between circulating inflammatory proteins and COVID-19 have been observed in previous cohorts. However, it is not unclear which circulating inflammatory proteins may boost the risk of or protect against COVID-19.
We performed Mendelian randomization (MR) analysis using GWAS summary result of 91 circulating inflammation-related proteins (N = 14,824) to assess their causal impact on severe COVID-19. The COVID-19 phenotypes encompassed both hospitalized (N = 2,095,324) and critical COVID-19 (N = 1,086,211). Moreover, sensitivity analyses were conducted to evaluate the robustness and reliability.
We found that seven circulating inflammatory proteins confer positive causal effects on severe COVID-19. Among them, serum levels of IL-10RB, FGF-19, and CCL-2 positively contributed to both hospitalized and critical COVID-19 conditions (OR: 1.10~1.16), while the other 4 proteins conferred risk on critical COVID-19 only (OR: 1.07~1.16), including EIF4EBP1, IL-7, NTF3, and LIF. Meanwhile, five proteins exert protective effects against hospitalization and progression to critical COVID-19 (OR: 0.85~0.95), including CXCL11, CDCP1, CCL4/MIP, IFNG, and LIFR. Sensitivity analyses did not support the presence of heterogeneity in the majority of MR analyses.
Our study revealed risk and protective inflammatory proteins for severe COVID-19, which may have vital implications for the treatment of the disease.
We performed Mendelian randomization (MR) analysis using GWAS summary result of 91 circulating inflammation-related proteins (N = 14,824) to assess their causal impact on severe COVID-19. The COVID-19 phenotypes encompassed both hospitalized (N = 2,095,324) and critical COVID-19 (N = 1,086,211). Moreover, sensitivity analyses were conducted to evaluate the robustness and reliability.
We found that seven circulating inflammatory proteins confer positive causal effects on severe COVID-19. Among them, serum levels of IL-10RB, FGF-19, and CCL-2 positively contributed to both hospitalized and critical COVID-19 conditions (OR: 1.10~1.16), while the other 4 proteins conferred risk on critical COVID-19 only (OR: 1.07~1.16), including EIF4EBP1, IL-7, NTF3, and LIF. Meanwhile, five proteins exert protective effects against hospitalization and progression to critical COVID-19 (OR: 0.85~0.95), including CXCL11, CDCP1, CCL4/MIP, IFNG, and LIFR. Sensitivity analyses did not support the presence of heterogeneity in the majority of MR analyses.
Our study revealed risk and protective inflammatory proteins for severe COVID-19, which may have vital implications for the treatment of the disease.
摘要：
■在以前的队列中已经观察到循环炎症蛋白与COVID-19之间的关系。然而,目前尚不清楚哪些循环炎症蛋白可能会增加COVID-19的风险或对COVID-19产生保护作用。
■我们使用91种循环炎症相关蛋白（N=14,824）的GWAS汇总结果进行了孟德尔随机化（MR）分析，以评估其对严重COVID-19的因果影响。COVID-19表型包括住院(N=2,095,324)和关键COVID-19(N=1,086,211)。此外，进行了敏感性分析，以评估其稳健性和可靠性。
■我们发现七种循环炎症蛋白对严重的COVID-19具有积极的因果效应。其中,血清IL-10RB水平,FGF-19和CCL-2对住院和危重的COVID-19有积极贡献（OR：1.10~1.16），而其他4种蛋白质仅对关键的COVID-19赋予风险（OR：1.07~1.16），包括EIF4EBP1、IL-7、NTF3和LIF。同时,五种蛋白对重症COVID-19的住院和进展具有保护作用(OR：0.85~0.95)，包括CXCL11、CDCP1、CCL4/MIP、IFNG,和LIFR。敏感性分析不支持大多数MR分析中存在异质性。
我们的研究揭示了严重COVID-19的风险和保护性炎症蛋白，这可能对该疾病的治疗具有重要意义。
■我们使用91种循环炎症相关蛋白（N=14,824）的GWAS汇总结果进行了孟德尔随机化（MR）分析，以评估其对严重COVID-19的因果影响。COVID-19表型包括住院(N=2,095,324)和关键COVID-19(N=1,086,211)。此外，进行了敏感性分析，以评估其稳健性和可靠性。
■我们发现七种循环炎症蛋白对严重的COVID-19具有积极的因果效应。其中,血清IL-10RB水平,FGF-19和CCL-2对住院和危重的COVID-19有积极贡献（OR：1.10~1.16），而其他4种蛋白质仅对关键的COVID-19赋予风险（OR：1.07~1.16），包括EIF4EBP1、IL-7、NTF3和LIF。同时,五种蛋白对重症COVID-19的住院和进展具有保护作用(OR：0.85~0.95)，包括CXCL11、CDCP1、CCL4/MIP、IFNG,和LIFR。敏感性分析不支持大多数MR分析中存在异质性。
我们的研究揭示了严重COVID-19的风险和保护性炎症蛋白，这可能对该疾病的治疗具有重要意义。
