Frost Joe N, Hamilton Fergus, Arnold David, Elvers Karen T, Shah Akshay, Armitage Andrew E, Milne Alice, McKernon Jorgen, Attwood Marie, Chen Yi-Ling, Xue Luzheng, Youngs Jonathan, Provine Nicholas M, Bicanic Tihana, Klenerman Paul, Drakesmith Hal, Ghazal Peter
MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX1 2JD, UK.
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, BS10 5NB, UK.
Wellcome Open Res. 2022 Jun 21;7:173. doi: 10.12688/wellcomeopenres.17904.1. eCollection 2022.
Marked reductions in serum iron concentrations are commonly induced during the acute phase of infection. This phenomenon, termed hypoferremia of inflammation, leads to inflammatory anemia, but could also have broader pathophysiological implications. In patients with coronavirus disease 2019 (COVID-19), hypoferremia is associated with disease severity and poorer outcomes, although there are few reported cohorts. In this study, we leverage a well characterised prospective cohort of hospitalised COVID-19 patients and perform a set of analyses focussing on iron and related biomarkers and both acute severity of COVID-19 and longer-term symptomatology. We observed no associations between acute serum iron and long-term outcomes (including fatigue, breathlessness or quality of life); however, lower haemoglobin was associated with poorer quality of life. We also quantified iron homeostasis associated parameters, demonstrating that among 50 circulating mediators of inflammation IL-6 concentrations were strongly associated with serum iron, consistent with its central role in inflammatory control of iron homeostasis. Surprisingly, we observed no association between serum hepcidin and serum iron concentrations. We also observed elevated erythroferrone concentrations in COVID-19 patients with anaemia of inflammation. These results enhance our understanding of the regulation and pathophysiological consequences of disturbed iron homeostasis during SARS-CoV-2 infection.
在感染急性期，血清铁浓度通常会显著降低。这种现象被称为炎症性低铁血症，会导致炎症性贫血，但也可能具有更广泛的病理生理意义。在2019冠状病毒病（COVID-19）患者中，尽管报告的队列较少，但低铁血症与疾病严重程度和较差的预后相关。在本研究中，我们利用一个特征明确的住院COVID-19患者前瞻性队列，进行了一系列分析，重点关注铁及相关生物标志物以及COVID-19的急性严重程度和长期症状。我们观察到急性血清铁与长期预后（包括疲劳、呼吸困难或生活质量）之间无关联；然而，血红蛋白水平较低与较差的生活质量相关。我们还对铁稳态相关参数进行了量化，表明在50种循环炎症介质中，白细胞介素-6浓度与血清铁密切相关，这与其在铁稳态炎症控制中的核心作用一致。令人惊讶的是，我们观察到血清铁调素与血清铁浓度之间无关联。我们还观察到患有炎症性贫血的COVID-19患者的促红细胞生成素浓度升高。这些结果增进了我们对SARS-CoV-2感染期间铁稳态紊乱的调节及其病理生理后果的理解。
