南非儿童通过五次 COVID-19 浪潮获得的天然免疫和对变异体的保护：前瞻性研究。

IF 4.8 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Infectious Diseases Pub Date : 2024-11-14 DOI:10.1016/j.ijid.2024.107300

Heather J. Zar , Lesley Workman , Rae MacGinty , Maresa Botha , Marina Johnson , Adam Hunt , Tiffany Burd , Mark P. Nicol , Stefan Flasche , Billy J. Quilty , David Goldblatt

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引用次数: 0

摘要

背景：在COVID-19大流行中，尽管儿童接触SARS-CoV-2的几率很高，但他们基本上没有患上严重疾病。人们对接触后的抗体反应及其在保护儿童免受后续变异感染方面的作用仍知之甚少：方法：对南非一个社区的儿童进行前瞻性队列研究，研究对象为经历祖先/贝塔/德尔塔/米克隆 BA.1/BA.2 和 BA.4/BA.5 SARS-CoV-2 浪潮（2020 年 3 月至 2022 年 10 月）的儿童。对求医行为/疾病进行记录，并通过 ECLIA 测量波后血清样本中对 Spike 的 IgG（CoV2-S-IgG）。为估计保护性 CoV2-S-IgG 临界值水平，拟合了逻辑函数来描述波前测量的 CoV2-S-IgG 与此后血清转换/升高概率的相关性：尽管疾病很少，但有 125/366 名儿童（34-2%）（中位年龄 6-7 岁（IQR 5.9-9 7-4 岁））在第 1 波后血清反应呈阳性，在第 2 波（贝塔）、第 3 波（德尔塔）、第 4 波和第 5 波（奥米克隆变异）后分别上升到 53-6%、76-0%、96-2% 和 99-2%。通过自然暴露诱导的 CoV2-S-IgG 对随后的 SARS-CoV-2 感染有保护作用，其中对 Beta 的保护作用最大，对 Omicron 的保护作用最小。祖先尖峰（S）抗原特异性 IgG 的水平为后续感染提供了 50%的保护阈值，其中 Beta 型最低，Omicron BA.1/BA.2 型最高。在多变量分析中，母亲血清阳性（aOR=2-57（95% CI：1-72；3-82））与儿童血清阳性密切相关：儿童对连续几波 SARS-CoV-2 产生了强烈的反应，对尖峰抗原产生了 IgG 反应，从而对随后的几波产生了保护作用。在没有接种疫苗的情况下，几乎所有儿童在第五波后血清反应都呈阳性，但没有人住院治疗，这表明仅靠自然免疫就足以在大流行环境中保护儿童：资金来源：英国国立卫生研究院GECO奖（GEC111）、惠康生物医学资源基金（221372/Z/20/Z）、惠康信托基金会非洲传染病研究中心（CIDRI）、美国比尔及梅林达-盖茨基金会（OPP1017641、OPP1017579）和美国国立卫生研究院H3非洲项目（U54HG009824、U01AI110466]。HZ 由南澳大利亚医学研究中心（SA-MRC）资助。MPN由澳大利亚国家健康与医学研究委员会研究员基金（APP1174455）资助。BJQ 由比尔及梅林达-盖茨基金会（Bill and Melinda Gates Foundation）资助（OPP1139859）。Stefan Flasche由威康信托基金会和英国皇家学会联合资助的亨利-戴尔爵士奖学金（资助编号208812/Z/17/Z）支持。

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Natural immunity and protection against variants in South African children through five COVID-19 waves: A prospective study

Objectives

Children have been largely spared from serious disease through the COVID-19 pandemic despite a high exposure to SARS-CoV-2. Antibody responses to exposure and their role in protecting children from subsequent variant infection remain poorly understood.

Methods

This is a prospective cohort study of children in a South African community through ancestral/Beta/Delta/Omicron BA.1/BA.2 and BA.4/BA.5 SARS-CoV-2 waves (March 2020-October 2022). Health seeking behavior/illness was recorded and postwave serum samples measured for immunoglobulin (Ig) G to spike (S) (CoV2-S-IgG) by electrochemiluminescent immunosorbent assay. To estimate the protective CoV2-S-IgG threshold levels, logistic functions were fit to describe the correlation of CoV2-S-IgG measured before a wave and the probability for seroconversion/boosting thereafter.

Results

Despite little disease, 125 per 366 (34.2%) children (median age 6.7 years [interquartile range 5.99-7.4 years]) were seropositive after wave I, rising to 53.6%, 76.0%, and 96.2% and 99.2% after waves II (Beta), III (Delta), and IV and V (Omicron variants), respectively. CoV2-S-IgG induced by natural exposure protected against subsequent SARS-CoV-2 infection, with the greatest protection for Beta and least for Omicron. The levels of IgG specific for ancestral S antigen that provided a 50% protective threshold for the subsequent wave were lowest for the Beta and highest for the Omicron BA.1/BA.2 wave. In the multivariate analysis, maternal seropositivity (adjusted odds ratio = 2.57 [95% confidence interval: 1.72-3.82]) was strongly associated with child seropositivity.

Conclusion

Children responded robustly to successive waves of SARS-CoV-2, mounting IgG responses to S antigen that were protective against subsequent waves. In the absence of vaccination, almost all children were seropositive after wave V but none were hospitalized, suggesting that natural immunity alone may be sufficient to protect children in a pandemic setting.

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来源期刊

International Journal of Infectious Diseases 医学-传染病学

CiteScore

18.90

自引率

2.40%

发文量

1020

审稿时长

30 days

期刊介绍： International Journal of Infectious Diseases (IJID) Publisher: International Society for Infectious Diseases Publication Frequency: Monthly Type: Peer-reviewed, Open Access Scope: Publishes original clinical and laboratory-based research. Reports clinical trials, reviews, and some case reports. Focuses on epidemiology, clinical diagnosis, treatment, and control of infectious diseases. Emphasizes diseases common in under-resourced countries.