自我报告的长期covid症状与IL-6信号相关因素（特别是IL-6R基因的rs2228145变体）之间关联的季节性变化：一项临床研究

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-02-22 DOI:10.1016/j.cyto.2025.156884

Katie Rees , Rebecca Aicheler , Lee Butcher , Alan Dodd , John Geen , Ceri Lynch , Isabel Massey , Keith Morris , Brian Tennant , Richard Webb

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引用次数: 0

摘要

本观察性研究的重点是白细胞介素-6 （IL-6）相关因素（特别是IL-6受体（IL-6R）基因的rs2228145多态性）对先前感染过COVID-19的个体的长期covid风险的影响。该研究的目的是更好地了解这些因素对长期covid风险的贡献，从而可能启动使用il -6相关因素作为预测风险的生物标志物的未来策略（同时也获得可能更广泛地影响长期covid管理和治疗的数据）。从175名先前经历过COVID-19感染的参与者中收集了DNA和血液样本，以及关于长期COVID-19症状（包括慢性疲劳和认知障碍）的问卷回答。评估自我报告的长期covid症状与参与者的rs2228145基因型（使用基于taqman的基因分型测定）和/或其循环IL-6、sIL-6R和sgp130水平（使用ELISA测定）之间的潜在关联。单变量回归分析表明，随着既往COVID-19感染的严重程度/数量以及高血压合并发病，出现长期COVID-19症状的几率增加，而疫苗接种降低了出现长期COVID-19的可能性。虽然长期covid患者比健康对照个体表现出更高的IL-6信号活性，但在整个研究队列中，rs2228145基因型与长期covid比值无关。在我们的数据集中确定了显著的季节变化后，根据获得样本/问卷回答的时间对整个研究队列进行分层。在由此产生的“夏季”亚队列中（而不是“冬季”亚队列中），rs2228145 AA基因型在表现出长时间covid症状的患者中显着过度代表，CC和AC基因型的长时间covid优势比显着降低。虽然解释因季节变化而复杂，但这些发现可能具有医学/生物医学价值。重要的是，由于IL-6在长期covid患者中高于健康对照组，并且在我们的“夏季”亚队列中携带rs2228145 AA基因型的个体患长期covid的风险较高，这些发现表明，未来可能使用IL-6和/或rs2228145基因型作为预测长期covid风险的生物标志物，这可能为长期covid的管理和治疗带来优势。

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Seasonal variation in the associations between self-reported long-COVID symptoms and IL-6 signalling-related factors (particularly the rs2228145 variant of the IL-6R gene): A clinical study.

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Seasonal variation in the associations between self-reported long-COVID symptoms and IL-6 signalling-related factors (particularly the rs2228145 variant of the IL-6R gene): A clinical study.

This observational study focused on the impact of Interleukin-6 (IL-6)-related factors (notably the IL-6 receptor (IL-6R) gene's rs2228145 polymorphism) on long-COVID risk in individuals who had previously experienced COVID-19 infection(s). The purpose of the study was to better understand such factors' contribution to long-COVID risk, and thus possibly initiate future strategies for using IL-6-related factors as biomarkers predictive of risk (while also obtaining data that may influence long-COVID management and treatment more generally).

DNA and blood samples, plus questionnaire responses regarding long-COVID symptoms (including chronic fatigue and cognitive impairment), were collected from 175 participants who had previously experienced COVID-19 infection(s). Potential associations between self-reported long-COVID symptoms and participants' rs2228145 genotypes (determined using TaqMan-based genotyping assays) and/or their circulating IL-6, sIL-6R and sgp130 levels (determined using ELISA) were evaluated.

Univariate-regression analyses demonstrated that odds of exhibiting long-COVID symptoms increased with severity/number of previous COVID-19 infection(s) and with hypertension as a co-morbidity, while vaccination decreased the likelihood of developing long-COVID. While long-COVID sufferers exhibited higher IL-6 signalling activity than healthy control individuals, rs2228145 genotype was not associated with long-COVID odds-ratios in- the entire-study cohort. Following identification of significant seasonal variations within our dataset, the entire-study cohort was stratified depending on when samples/questionnaire responses were obtained. In the resulting ‘summer’ sub-cohort (but not the ‘winter’ sub-cohort), the rs2228145 AA genotype was significantly over-represented amongst those exhibiting long-COVID symptoms, and long-COVID odds-ratios were significantly reduced for the CC and AC genotypes.

While interpretation is complicated by seasonal variations, these findings may be of medical/biomedical value. Importantly, as IL-6 was higher in long-COVID sufferers than healthy controls, and rs2228145 AA genotype-bearing individuals within our ‘summer’ sub-cohort were at elevated risk of developing long-COVID, these findings point towards possible future use of IL-6 and/or rs2228145 genotype as biomarkers predictive of long-COVID risk, which may bring advantages regarding management and treatment of long-COVID.

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.