Reduced IFNL1 and/or IFNL2, but not IFNL3 is associated with worse outcome in patients with COVID-19.

IF 3.4 3区 医学 Q3 IMMUNOLOGY Clinical and experimental immunology Pub Date : 2024-07-02 DOI:10.1093/cei/uxae047
Elena Woods, Adriana Mena, Sophie Sierpinska, Emily Carr, Richard Hagan, John Crowley, Colm Bergin, David Clark, Caroline Brophy, Derek Macallan, Clair M Gardiner
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Abstract

The recent pandemic was caused by the emergence of a new human pathogen, SARS-CoV-2. While the rapid development of many vaccines provided an end to the immediate crisis, there remains an urgent need to understand more about this new virus and what constitutes a beneficial immune response in terms of successful resolution of infection. Indeed, this is key for development of vaccines that provide long lasting protective immunity. The interferon lambda (IFNL) family of cytokines are produced early in response to infection and are generally considered anti-viral and beneficial. However, data regarding production of IFNL cytokines in COVID-19 patients is highly variable, and generally from underpowered studies. In this study, we measured all three IFNL1, IFNL2 and IFNL3 cytokines in plasma from a well characterised, large COVID-19 cohort (n=399) that included good representation from patients with a more indolent disease progression, and hence a beneficial immune response. While all three cytokines were produced, they differed in both the frequency of expression in patients, and the levels produced. IFNL3 was produced in almost all patients but neither protein level nor IFNL3/IFNL4 SNPs were associated with clinical outcome. In contrast, both IFNL1 and IFNL2 levels were significantly lower, or absent, in plasma of patients that had a more severe disease outcome. These data are consistent with the concept that early IFNL1 and IFNL2 cytokine production is protective against SARS-CoV-2 infection.

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IFNL1 和/或 IFNL2(而非 IFNL3)的降低与 COVID-19 患者的预后较差有关。
最近的大流行是由一种新的人类病原体 SARS-CoV-2 引起的。虽然许多疫苗的快速开发结束了这场直接危机,但人们仍然迫切需要更多地了解这种新病毒,以及什么是成功解决感染的有益免疫反应。事实上,这是开发可提供长期保护性免疫的疫苗的关键。λ干扰素(IFNL)系列细胞因子在感染早期就会产生,通常被认为是抗病毒和有益的。然而,有关 COVID-19 患者 IFNL 细胞因子产生情况的数据变化很大,而且一般都是来自幂等不足的研究。在这项研究中,我们测量了一个特征明确、规模庞大的 COVID-19 患者群(人数=399)血浆中的所有三种 IFNL1、IFNL2 和 IFNL3 细胞因子,其中包括病情发展较为缓和的患者,因此他们的免疫反应是有益的。虽然所有三种细胞因子都会产生,但它们在患者体内的表达频率和产生水平都有所不同。几乎所有患者都会产生 IFNL3,但蛋白水平和 IFNL3/IFNL4 SNPs 都与临床结果无关。相比之下,在病情较重的患者血浆中,IFNL1 和 IFNL2 的水平明显较低或不存在。这些数据与早期 IFNL1 和 IFNL2 细胞因子的产生对 SARS-CoV-2 感染具有保护作用的观点一致。
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来源期刊
CiteScore
8.40
自引率
2.20%
发文量
101
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.
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