免疫加速老化与 COVID-19 疾病的严重程度有关

IF 5.2 2区 医学 Q1 GERIATRICS & GERONTOLOGY
Janet M. Lord, Tonny Veenith, Jack Sullivan, Archana Sharma-Oates, Alex G. Richter, Neil J. Greening, Hamish J. C. McAuley, Rachael A. Evans, Paul Moss, Shona C. Moore, Lance Turtle, Nandan Gautam, Ahmed Gilani, Manan Bajaj, Louise V. Wain, Christopher Brightling, Betty Raman, Michael Marks, Amisha Singapuri, Omer Elneima, Peter J. M. Openshaw, Niharika A. Duggal
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引用次数: 0

摘要

老年人 COVID-19 严重程度的显著增加是免疫衰老(与年龄有关的免疫系统重塑)的一个明显例子。为了更好地描述康复期免疫衰老与急性疾病严重程度之间的关系,我们测定了 COVID-19 幸存者和非感染对照组的免疫表型。我们对从 103 名 COVID-19 幸存者身上分离的外周血单核细胞进行了详细的免疫表型分析,这些幸存者在康复后 3-5 个月被分为重度(56 人;年龄为 53.12 ± 11.30 岁)、中度(32 人;年龄为 52.28 ± 11.43 岁)或轻度(15 人;年龄为 49.67 ± 7.30 岁),并与年龄和性别匹配的健康成人(59 人;年龄为 50.49 ± 10.68 岁)进行了比较。我们对多种免疫细胞表型进行了评估,得出了一个综合评分 IMM-AGE,以确定免疫衰老的程度。与对照组相比,我们发现严重 COVID-19 幸存者的免疫衰老特征增加,包括:幼稚 CD4 和 CD8 T 细胞的频率和数量减少(p < 0.0001);EMRA CD4(p < 0.003)和 CD8 T 细胞的频率增加(p < 0.001);CD28-ve T 细胞的频率(p < 0.0001)和绝对数量(p < 0.001);CD28-ve CD57+ve 衰老的 CD4 和 CD8 T 细胞的频率更高(p < 0.003),绝对数量更多(p < 0.02);PD-1 表达衰竭的 CD8 T 细胞的频率更高(p < 0.003),绝对数量更多(p < 0.02);Th17 极化增加了两倍(p < 0.0001);记忆 B 细胞的频率更高(p < 0.001),CD57+ve 衰老的 NK 细胞的频率增加(p < 0.0001),数量增加(p < 0.001)。因此,重度 COVID-19 幸存者的 IMM-AGE 评分明显高于对照组(p < 0.001)。中度患者的差异很小,轻度患者则没有差异。回归分析表明,影响 IMM-AGE 评分的唯一先存变量是南亚种族($$\beta$$ = 0.174,p = 0.043),主要影响因素是疾病严重程度($$\beta$$ = 0.188,p = 0.01)。我们的分析表明,在严重 COVID-19 的幸存者中存在着免疫老化增强的状态,这可能与 SARS-Cov-2 感染有关。我们的数据支持对这些重症患者进行抗免疫老化干预试验以改善临床疗效的理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Accelarated immune ageing is associated with COVID-19 disease severity
The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( $$\beta$$ = 0.174, p = 0.043), with a major influence being disease severity ( $$\beta$$ = 0.188, p = 0.01). Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease.
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来源期刊
Immunity & Ageing
Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY
CiteScore
10.20
自引率
3.80%
发文量
55
期刊介绍: Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.
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