The kynurenine pathway relates to post-acute COVID-19 objective cognitive impairment and PASC

IF 4.4 2区医学 Q1 CLINICAL NEUROLOGY

Annals of Clinical and Translational Neurology Pub Date : 2023-06-15 DOI:10.1002/acn3.51825

Lucette A. Cysique, David Jakabek, Sophia G. Bracken, Yasmin Allen-Davidian, Benjamin Heng, Sharron Chow, Mona Dehhaghi, Ananda Staats Pires, David R. Darley, Anthony Byrne, Chansavath Phetsouphanh, Anthony Kelleher, Gregory J. Dore, Gail V. Matthews, Gilles J. Guillemin, Bruce J. Brew

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引用次数: 6

Abstract

Objective

To determine the prevalence and natural history of post-acute COVID-19 objective cognitive impairment and function, and their relationship to demographic, clinical factors, post-acute sequelae of COVID-19 (PASC), and biomarkers.

Methods

A total of 128 post-acute COVID-19 patients (age = 46 ± 15; 42% women, acute disease severity: not hospitalized: 38.6% mild: 0–1 symptoms, 52% 2+ symptoms; 9.4% hospitalized) completed standard cognition, olfaction, and mental health examinations 2-, 4-, and 12-month post diagnosis. Over the same time frame, WHO-defined PASC was determined. Blood cytokines, peripheral neurobiomarkers, and kynurenine pathway (KP) metabolites were measured. Objective cognitive function was demographically/practice corrected, and impairment prevalence was determined using the evidence-based Global Deficit Score method to detect at least mild cognitive impairment (GDS > 0.5). Linear mixed effect regression models with time effect (month post diagnosis) evaluated the relationships to cognition.

Results

Across the 12-month study period, mild to moderate cognitive impairment ranged from 16% to 26%, and 46.5% were impaired at least once. Impairment associated with poorer work capacity (p < 0.05), and 2-month objectively tested anosmia (p < 0.05). PASC with (p = 0.01) and without disability (p < 0.03) associated with acute COVID-19 severity. KP measures showed prolonged activation (2 to 8 months) (p < 0.0001) linked to IFN-beta in those with PASC. Of the blood analytes, only the KP metabolites (elevated quinolinic acid, 3-hydroxyanthranilic acid, kynurenine, the kynurenine/tryptophan ratio) associated (p < 0.001) with poorer cognitive performance and greater likelihood of impairment. PASC, independent of disability associated with abnormal kynurenine/tryptophan (p < 0.03).

Interpretation

The kynurenine pathway relates to post-acute COVID-19 objective cognitive impairment and PASC, thereby enabling biomarker and therapeutic possibilities.

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犬尿氨酸通路与急性后COVID-19客观认知障碍和PASC有关

目的了解新冠肺炎急性后客观认知功能障碍的患病率、自然病史及其与人口统计学、临床因素、新冠肺炎急性后后遗症(PASC)和生物标志物的关系。方法128例急性后COVID-19患者(年龄= 46±15;42%的女性，急性疾病严重程度:未住院;38.6%轻度:0-1症状，52% 2+症状;(9.4%住院)在诊断后2个月、4个月和12个月完成标准的认知、嗅觉和精神健康检查。在同一时间框架内，确定了世卫组织定义的PASC。测量血液细胞因子、周围神经生物标志物和犬尿氨酸途径(KP)代谢物。对客观认知功能进行人口学/实践校正，并使用基于证据的全球缺陷评分方法确定障碍患病率，以检测至少轻度认知障碍(GDS > 0.5)。具有时间效应(诊断后一个月)的线性混合效应回归模型评估了与认知的关系。结果在12个月的研究期间，轻度至中度认知障碍的比例为16%至26%，46.5%的患者至少有一次认知障碍。与较差的工作能力相关的损害(p < 0.05)，以及2个月客观测试的嗅觉缺失(p < 0.05)。伴有(p = 0.01)和无残疾(p < 0.03)的PASC与COVID-19急性严重程度相关。KP测量显示，PASC患者的ifn - β激活时间延长(2至8个月)(p < 0.0001)。在血液分析中，只有KP代谢物(升高的喹啉酸、3-羟基苯甲酸、犬尿氨酸、犬尿氨酸/色氨酸比率)与较差的认知能力和更大的损害可能性相关(p < 0.001)。PASC与犬尿氨酸/色氨酸异常相关的残疾无关(p < 0.03)。犬尿氨酸途径与急性后COVID-19客观认知障碍和PASC有关，从而使生物标志物和治疗成为可能。

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来源期刊

Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)

CiteScore

9.10

自引率

1.90%

发文量

218

审稿时长

8 weeks

期刊介绍： Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.