SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study.
SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study.
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DOI：
10.3389/fimmu.2023.1146702
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发表时间：
2023
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大流行使得能够分析针对感染免疫学幼稚个体的新型冠状病毒诱导的免疫应答。这为分析免疫反应以及与年龄、性别和疾病严重程度的关联提供了机会。在这里，我们测量了ISARIC 4C队列参与者（n=337）的固相结合抗体和病毒中和抗体（nAb）反应的阵列，并描述了它们与急性感染和早期恢复期间疾病严重程度峰值的相关性。总体而言，双抗原结合试验（DABA）中针对受体结合结构域抗体（抗RBD）的应答与针对病毒刺突、S1和核衣壳蛋白（NP）抗原的IgM和IgG应答相关性良好。DABA反应性也与nAb相关。正如我们和其他人以前报道的那样，老年男性患严重疾病和死亡的风险更大，而在年轻人中，每个严重程度组的性别比例相同。在患有严重疾病的老年男性（平均年龄68岁）中，与女性相比，发现抗体水平峰值延迟一到两周，并且nAb反应进一步延迟。此外，我们证明，固相结合抗体反应达到更高的水平，在男性通过DABA和IgM结合对刺突，NP和S1抗原。相比之下，对于nAb应答未观察到这一点。当在招募时测量鼻拭子中的SARS-CoV-2 RNA转录物（作为病毒脱落的替代物）时，我们没有发现性别或疾病严重程度的显著差异。然而，我们已经显示与低鼻病毒RNA相关的较高抗体水平，表明抗体应答在控制上呼吸道中的病毒复制和脱落中的作用。在这项研究中，我们发现男性和女性之间的体液免疫反应存在明显差异，这些差异与年龄以及由此产生的疾病严重程度有关。
The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.
影响因子：
13.2
作者：
Shen L;Wang C;Zhao J;Tang X;Shen Y;Lu M;Ding Z;Huang C;Zhang J;Li S;Lan J;Wong G;Zhu Y
通讯作者：
Zhu Y