A Public Health Antibody Screening Indicates a 6-Fold Higher SARS-CoV-2 Exposure Rate than Reported Cases in Children.
A Public Health Antibody Screening Indicates a 6-Fold Higher SARS-CoV-2 Exposure Rate than Reported Cases in Children.
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DOI：
10.1016/j.medj.2020.10.003
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发表时间：
2021-02-12
期刊：
影响因子：
--
通讯作者：
Ziegler AG
中科院分区：
文献类型：
--
作者：
Hippich M;Holthaus L;Assfalg R;Zapardiel-Gonzalo J;Kapfelsperger H;Heigermoser M;Haupt F;Ewald DA;Welzhofer TC;Marcus BA;Heck S;Koelln A;Stock J;Voss F;Secchi M;Piemonti L;de la Rosa K;Protzer U;Boehmer M;Achenbach P;Lampasona V;Bonifacio E;Ziegler AG
对病毒的抗体反应反映了暴露和潜在的保护作用。我们开发了一种高度特异性和敏感性的方法来测量针对SARS-CoV-2的抗体，用于人群规模的免疫监测。抗体阳性定义为对SARS-CoV-2的受体结合域和核衣壳蛋白的双重阳性反应。通过免疫沉淀法测定了来自德国巴伐利亚州的15，771名1至18岁儿童的毛细血管血中的抗体，这些儿童参加了公共卫生1型糖尿病筛查项目（ClinicalTrials.gov：NCT 04039945），在巴伐利亚州的一项筛查研究中，对1，916个新生儿干血斑进行了检测（ClinicalTrials.gov：NCT 03316261）和75名SARS-CoV-2阳性个体。从巴伐利亚卫生当局数据中获得病毒阳性发生率。在2019年的3，887名儿童中没有检测到双抗体阳性（100%特异性），75名SARS-CoV-2阳性个体中有73名（97.3%灵敏度）。2020年儿童抗体监测结果显示，1 - 3月、4月、5月、6月和7月的频率分别为0.08%、0.61%、0.74%、1.13%和0.91%。自2020年4月以来，抗体流行率比当局报告的病例发生率高6倍（每10万名儿童中有156例），在巴伐利亚州的7个地区之间存在显著差异（p < 0.0001），并且与年龄或性别无关。病毒阳性家庭成员的儿童传播率为35%。47%的阳性儿童无症状。未观察到与1型糖尿病自身免疫相关。新生儿抗体阳性率为0.47%。我们证明了以人群为基础的筛查计划对大流行监测的价值。这项工作得到了BMBF（FKZ 01 KX 1818）的资助。儿童的SARS-CoV-2感染率低于成人。监测儿童等低发病率人群需要高度特异性的方法。我们开发了一种特异性（100%）和敏感性（>95%）的策略来检测SARS-CoV-2抗体作为感染的衡量标准。德国巴伐利亚州在2020年期间对超过11，000名儿童进行的公共卫生抗体监测发现，4月至7月的抗体频率为0. 87%，比卫生当局报告的SARS-CoV-2儿童发病率高出6倍。有一个很大的区域差异抗体频率，但没有年龄或性别差异观察。病毒阳性家庭中的儿童传播率为35%。问卷调查数据表明，将病毒检测限制在有症状或SARS-CoV-2阳性接触者的儿童中，将错过所有儿童病例的25%。Hippich等人建立了一种高度特异性和敏感性的双重抗体策略，用于SARS-CoV-2抗体流行的公共卫生监测。在对德国11，000多名儿童进行检测时，他们报告的抗体流行率是卫生当局报告的SARS-CoV-2发病率的6倍，其中包括50%没有症状的抗体阳性儿童。
Antibody responses to virus reflect exposure and potential protection. We developed a highly specific and sensitive approach to measuring antibodies against SARS-CoV-2 for population-scale immune surveillance. Antibody positivity was defined as a dual-positive response against both the receptor-binding domain and nucleocapsid proteins of SARS-CoV-2. Antibodies were measured by immunoprecipitation assays in capillary blood from 15,771 children aged 1 to 18 years living in Bavaria, Germany, and participating in a public health type 1 diabetes screening program (ClinicalTrials.gov: NCT04039945), in 1,916 dried blood spots from neonates in a Bavarian screening study (ClinicalTrials.gov: NCT03316261), and in 75 SARS-CoV-2-positive individuals. Virus positive incidence was obtained from the Bavarian health authority data. Dual-antibody positivity was detected in none of the 3,887 children in 2019 (100% specificity) and 73 of 75 SARS-CoV-2-positive individuals (97.3% sensitivity). Antibody surveillance in children during 2020 resulted in frequencies of 0.08% in January to March, 0.61% in April, 0.74% in May, 1.13% in June, and 0.91% in July. Antibody prevalence from April 2020 was 6-fold higher than the incidence of authority-reported cases (156 per 100,000 children), showed marked variation between the seven Bavarian regions (p < 0.0001), and was not associated with age or sex. Transmission in children with virus-positive family members was 35%. 47% of positive children were asymptomatic. No association with type 1 diabetes autoimmunity was observed. Antibody frequency in newborns was 0.47%. We demonstrate the value of population-based screening programs for pandemic monitoring. The work was supported by funding from the BMBF (FKZ01KX1818). Children are shown to have lower rates of SARS-CoV-2 infection than adults. Monitoring low incidence populations such as children requires highly specific methods. We developed a specific (100%) and sensitive (>95%) strategy to detect SARS-CoV-2 antibodies as a measure of infection. Public health antibody surveillance in over 11,000 children in Bavaria, Germany during 2020 found an antibody frequency of 0.87% from April to July, which was 6-fold higher than the health authority-reported SARS-CoV-2 incidence in children. There was a large regional variation in antibody frequency, but no age or sex differences were observed. Transmission to children within virus-positive families was 35%. Questionnaire data suggested that limiting virus testing to children with symptoms or SARS-CoV-2-positive contact would miss 25% of all childhood cases. Hippich et al. developed a highly specific and sensitive dual antibody strategy for public health surveillance of SARS-CoV-2 antibody prevalence. In testing more than 11,000 children in Germany, they report an antibody prevalence that is 6-fold higher than the health authority-reported SARS-CoV-2 incidence, including 50% of antibody-positive children without symptoms.
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