Levels of soluble complement regulators predict severity of COVID-19 symptoms.
Levels of soluble complement regulators predict severity of COVID-19 symptoms.
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可溶性补体调节器的水平预测了199症状的严重程度。
DOI：
10.3389/fimmu.2022.1032331
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
SARS-CoV-2病毒继续在全球范围内造成COVID-19的显著发病率和死亡率。患者管理的主要挑战之一是观察到的广泛症状。虽然大多数人的病情相对较轻，但仍有极少数患者需要住院治疗，其中COVID-19仍对一些人造成致命影响。因此，仍然迫切需要更好地了解这种严重疾病的驱动因素，无论是在潜在的生物学方面，还是在诊断时预测哪些患者可能需要进一步干预，从而为患者和医疗保健系统带来更好的结果。多项证据表明，补体级联反应失调是严重COVID-19结果的主要因素。这是如何在机械上得到支持的尚不清楚。在这里，我们集中在可溶性补体调节因子补体H（FH），其剪接变体因子H样1（FHL-1）和五个因子H相关蛋白（FHR 1 -5）的作用。使用靶向质谱法，我们在诊断时采集的对照组和SARS-CoV-2患者的188份血浆样本中定量了这些蛋白质。该分析显示，在患有更严重疾病的患者中，所有FHR蛋白均显著升高，但FH没有，特别是FHR 2和FHR 5（FHR 2：1.97倍，p<0.0001; FHR 5：2.4倍，p<0.0001）。此外，对于77例SARS-CoV-2 +ve患者的亚组，我们还分析了诊断后约28天采集的时程样本。在这里，我们看到补体调节因子水平在所有无症状或轻度疾病的个体中下降，但在那些具有更严重结果的个体中，调节因子水平仍然很高，该组中FHR 2水平高于基线水平。这些数据支持以下假设：FHR家族蛋白循环水平的升高可以预测COVID-19患者的疾病严重程度，并且升高的持续时间（或缺乏免疫激活解决方案）可能是导致COVID-19不良结局的部分原因。
The SARS-CoV-2 virus continues to cause significant morbidity and mortality worldwide from COVID-19. One of the major challenges of patient management is the broad range of symptoms observed. While the majority of individuals experience relatively mild disease, a significant minority of patients require hospitalisation, with COVID-19 still proving fatal for some. As such, there remains a desperate need to better understand what drives this severe disease, both in terms of the underlying biology, but also to potentially predict at diagnosis which patients are likely to require further interventions, thus enabling better outcomes for both patients and healthcare systems. Several lines of evidence have pointed to dysregulation of the complement cascade as a major factor in severe COVID-19 outcomes. How this is underpinned mechanistically is not known. Here, we have focussed on the role of the soluble complement regulators Complement Factor H (FH), its splice variant Factor H-like 1 (FHL-1) and five Factor H-Related proteins (FHR1-5). Using a targeted mass spectrometry approach, we quantified these proteins in a cohort of 188 plasma samples from controls and SARS-CoV-2 patients taken at diagnosis. This analysis revealed significant elevations in all FHR proteins, but not FH, in patients with more severe disease, particularly FHR2 and FHR5 (FHR2: 1.97-fold, p<0.0001; FHR5: 2.4-fold, p<0.0001). Furthermore, for a subset of 77 SARS-CoV-2 +ve patients we also analysed time course samples taken approximately 28 days post-diagnosis. Here, we see complement regulator levels drop in all individuals with asymptomatic or mild disease, but regulators remain high in those with more severe outcomes, with elevations in FHR2 over baseline levels in this group. These data support the hypothesis that elevation of circulating levels of the FHR family of proteins could predict disease severity in COVID-19 patients, and that the duration of elevation (or lack of immune activation resolution) may be partly responsible for driving poor outcomes in COVID-19.
影响因子：
7.3
作者：
Xu B;Kang Y;Du Y;Guo W;Zhu L;Zhang H
通讯作者：
Zhang H