Infectious Disease Epidemiology and Analytics Unit, Department of Global Health, Institut Pasteur, Paris, France; Malaria: Parasites and Hosts Unit, Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France.
Infectious Disease Epidemiology and Analytics Unit, Department of Global Health, Institut Pasteur, Paris, France; Malaria: Parasites and Hosts Unit, Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France.
EBioMedicine. 2021 Aug;70:103495. doi: 10.1016/j.ebiom.2021.103495. Epub 2021 Jul 23.
Children are underrepresented in the COVID-19 pandemic and often experience milder disease than adolescents and adults. Reduced severity is possibly due to recent and more frequent seasonal human coronaviruses (HCoV) infections. We assessed the seroprevalence of SARS-CoV-2 and seasonal HCoV specific antibodies in a large cohort in north-eastern France.
In this cross-sectional seroprevalence study, serum samples were collected from children and adults requiring hospital admission for non-COVID-19 between February and August 2020. Antibody responses to SARS-CoV-2 and seasonal HCoV (229E, HKU1, NL63, OC43) were assessed using a bead-based multiplex assay, Luciferase-Linked ImmunoSorbent Assay, and a pseudotype neutralisation assay.
In 2,408 individuals, seroprevalence of SARS-CoV-2-specific antibodies was 7-8% with three different immunoassays. Antibody levels to seasonal HCoV increased substantially up to the age of 10. Antibody responses in SARS-CoV-2 seropositive individuals were lowest in adults 18-30 years. In SARS-CoV-2 seronegative individuals, we observed cross-reactivity between antibodies to the four HCoV and SARS-CoV-2 Spike. In contrast to other antibodies to SARS-CoV-2, specific antibodies to sub-unit 2 of Spike (S2) in seronegative samples were highest in children. Upon infection with SARS-CoV-2, antibody levels to Spike of betacoronavirus OC43 increased across the whole age spectrum. No SARS-CoV-2 seropositive individuals with low levels of antibodies to seasonal HCoV were observed.
Our findings underline significant cross-reactivity between antibodies to SARS-CoV-2 and seasonal HCoV, but provide no significant evidence for cross-protective immunity to SARS-CoV-2 infection due to a recent seasonal HCoV infection. In particular, across all age groups we did not observe SARS-CoV-2 infected individuals with low levels of antibodies to seasonal HCoV.
This work was supported by the « URGENCE COVID-19 » fundraising campaign of Institut Pasteur, by the French Government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (Grant No. ANR-10-LABX-62-IBEID), and by the REACTing (Research & Action Emerging Infectious Diseases), and by the RECOVER project funded by the European Union's Horizon 2020 research and innovation programme under grant agreement No. 101003589, and by a grant from LabEx IBEID (ANR-10-LABX-62-IBEID).
儿童在 COVID-19 大流行中代表性不足，且通常比青少年和成年人患病较轻。严重程度降低可能是由于最近更频繁的季节性人类冠状病毒（HCoV）感染。我们评估了法国东北部一个大型队列中 SARS-CoV-2 和季节性 HCoV 特异性抗体的血清流行率。
在这项横断面血清流行率研究中，于 2020 年 2 月至 8 月间采集了因非 COVID-19 而住院的儿童和成人的血清样本。使用基于珠的多重分析、荧光素酶联免疫吸附试验和假型中和试验评估了针对 SARS-CoV-2 和季节性 HCoV（229E、HKU1、NL63、OC43）的抗体反应。
在 2408 名个体中，三种不同免疫测定法的 SARS-CoV-2 特异性抗体血清流行率为 7-8%。季节性 HCoV 的抗体水平在 10 岁之前显著增加。SARS-CoV-2 血清阳性个体中，18-30 岁成年人的抗体水平最低。在 SARS-CoV-2 血清阴性个体中，我们观察到针对四种 HCoV 和 SARS-CoV-2 刺突的抗体之间存在交叉反应。与 SARS-CoV-2 的其他抗体不同，血清阴性样本中针对 Spike 亚单位 2（S2）的特异性抗体水平在儿童中最高。感染 SARS-CoV-2 后，β冠状病毒 OC43 的 Spike 抗体水平在整个年龄范围内均增加。未观察到 SARS-CoV-2 血清阳性个体且季节性 HCoV 抗体水平低的情况。
我们的研究结果强调了 SARS-CoV-2 和季节性 HCoV 之间的显著交叉反应，但由于最近的季节性 HCoV 感染，没有提供 SARS-CoV-2 感染交叉保护免疫的显著证据。特别是，在所有年龄组中，我们均未观察到 SARS-CoV-2 感染个体且季节性 HCoV 抗体水平低的情况。
这项工作得到了巴斯德研究所的“COVID-19 紧急”筹款活动、法国政府的“未来投资”计划、卓越实验室综合新发传染病生物学（ANR-10-LABX-62-IBEID 赠款）以及 REACTing（研究与行动新兴传染病）的支持，并得到了欧盟地平线 2020 研究与创新计划的 RECOVER 项目（赠款协议号 101003589）和 LabEx IBEID（ANR-10-LABX-62-IBEID）的资助。
