Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran.
Infection. 2024 Oct;52(5):2043-2059. doi: 10.1007/s15010-024-02293-y. Epub 2024 May 27.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly contagious respiratory disease Corona Virus Disease 2019 (COVID-19) that may lead to various neurological and psychological disorders that can be acute, lasting days to weeks or months and possibly longer. The latter is known as long-COVID or more recently post-acute sequelae of COVID (PASC). During acute COVID-19 infection, a strong inflammatory response, known as the cytokine storm, occurs in some patients. The levels of interferon-γ (IFN-γ), interferon-β (IFN-β), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) are particularly increased. These cytokines are known to activate the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), catalysing the first step of tryptophan (Trp) catabolism through the kynurenine pathway (KP) leading to the production of several neurotoxic and immunosuppressive metabolites. There is already data showing elevation in KP metabolites both acutely and in PASC, especially regarding cognitive impairment. Thus, it is likely that KP involvement is significant in SARS-CoV-2 pathogenesis especially neurologically.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是高度传染性呼吸道疾病 2019 年冠状病毒病（COVID-19）的病原体，它可能导致各种神经系统和心理障碍，这些障碍可能是急性的，持续数天到数周或数月，甚至更长时间。后者被称为长 COVID 或最近的 COVID 后急性后遗症（PASC）。在急性 COVID-19 感染期间，一些患者会发生强烈的炎症反应，称为细胞因子风暴。干扰素-γ（IFN-γ）、干扰素-β（IFN-β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平特别升高。这些细胞因子已知可激活酶吲哚胺 2,3-双加氧酶 1（IDO-1），通过犬尿氨酸途径（KP）催化色氨酸（Trp）分解代谢的第一步，导致产生几种神经毒性和免疫抑制代谢物。已经有数据显示 KP 代谢物在急性和 PASC 中都升高，特别是在认知障碍方面。因此，KP 的参与很可能在 SARS-CoV-2 的发病机制中起重要作用，尤其是在神经系统方面。
