Background We examined effects of single-nucleotide variants (SNVs) of IL1RN, the gene encoding the anti-inflammatory interleukin 1 receptor antagonist (IL-1Ra), on the cytokine release syndrome (CRS) and mortality in patients with acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods IL1RN CTA haplotypes formed from 3 SNVs (rs419598, rs315952, rs9005) and the individual SNVs were assessed for association with laboratory markers of inflammation and mortality. We studied 2589 patients hospitalized with SARS-CoV-2 between March 2020 and March 2021. Results Mortality was 15.3% and lower in women than men (13.1% vs 17.3%, P = .0003). Carriers of the CTA-1/2 IL1RN haplotypes exhibited decreased inflammatory markers and increased plasma IL-1Ra. Evaluation of the individual SNVs of the IL1RN, carriers of the rs419598 C/C SNV exhibited significantly reduced inflammatory biomarker levels and numerically lower mortality compared to the C/T-T/T genotype (10.0% vs 17.8%, P = .052) in men, with the most pronounced association observed in male patients ≤74 years old, whose mortality was reduced by 80% (3.1% vs 14.0%, P = .030). Conclusions The IL1RN haplotype CTA and C/C variant of rs419598 are associated with attenuation of the CRS and decreased mortality in men with acute SARS-CoV-2 infection. The data suggest that the IL1RN pathway modulates the severity of coronavirus disease 2019 (COVID-19) via endogenous anti-inflammatory mechanisms.

中文翻译：

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Interleukin-1 受体拮抗剂基因 (IL1RN) 变异体调节细胞因子释放综合征和 COVID-19 死亡率


背景 我们研究了 IL1RN（编码抗炎白细胞介素 1 受体拮抗剂 (IL-1Ra) 的基因）的单核苷酸变异 (SNV) 对急性严重呼吸综合征冠状病毒患者的细胞因子释放综合征 (CRS) 和死亡率的影响2（SARS-CoV-2）感染。方法评估由 3 个 SNV（rs419598、rs315952、rs9005）形成的 IL1RN CTA 单倍型以及各个 SNV 与炎症和死亡率实验室标志物的关联。我们研究了 2020 年 3 月至 2021 年 3 月期间住院的 2589 名 SARS-CoV-2 患者。结果女性死亡率为 15.3%，低于男性（13.1% vs 17.3%，P = .0003）。 CTA-1/2 IL1RN 单倍型的携带者表现出炎症标志物减少和血浆 IL-1Ra 增加。对 IL1RN 的个体 SNV 进行评估，与 C/TT/T 基因型相比，男性中 rs419598 C/C SNV 的携带者表现出显着降低的炎症生物标志物水平和较低的死亡率（10.0% vs 17.8%，P = .052） ，在 ≤74 岁的男性患者中观察到最明显的关联，其死亡率降低了 80%（3.1% vs 14.0%，P = .030）。结论 IL1RN 单倍型 CTA 和 rs419598 的 C/C 变体与急性 SARS-CoV-2 感染男性的 CRS 减弱和死亡率降低相关。数据表明，IL1RN 通路通过内源性抗炎机制调节 2019 年冠状病毒病 (COVID-19) 的严重程度。