年龄相关的冠状病毒抗体血清阳性率：2013 年和 2020 年加拿大不列颠哥伦比亚省的基于人群的血清学调查。

BACKGROUND: Older adults have been disproportionately affected during the SARS-CoV-2 pandemic, including higher risk of severe disease and long-COVID. Prior exposure to endemic human coronaviruses (HCoV) may modulate the response to SARS-CoV-2 infection and contribute to age-related observations. We hypothesized that cross-reactive antibodies to SARS-CoV-2 are associated with antibodies to HCoV and that both increase with age. METHODS: To assess SARS-CoV-2 unexposed individuals, we drew upon archived anonymized residual sero-surveys conducted in British Columbia (BC), Canada, including before SARS-CoV-2 emergence (May, 2013) and before widespread community circulation in BC (May, 2020). Fifty sera, sex-balanced per ten-year age band, were sought among individuals ≤10 to ≥80 years old, supplemented as indicated by sera from March and September 2020. Sera were tested on the Meso Scale Diagnostics (MSD) electrochemiluminescent multiplex immunoassay to quantify IgG antibody against the Spike proteins of HCoV, including alpha (HCoV-229E, HCoV-NL63) and beta (HCoV-HKU1, HCoV-OC43) viruses, and the 2003 epidemic beta coronavirus, SARS-CoV-1. Cross-reactive antibodies to Spike, Nucleocapsid, and the Receptor Binding Domain (RBD) of SARS-CoV-2 were similarly measured, with SARS-CoV-2 sero-positivity overall defined by positivity on ≥2 targets. RESULTS: Samples included 407 sera from 2013, of which 17 were children ≤10 years. The 2020 samples included 488 sera, of which 88 were children ≤10 years. Anti-Spike antibodies to all four endemic HCoV were acquired by 10 years of age. There were 20/407 (5%) sera in 2013 and 8/488 (2%) in 2020 that were considered sero-positive for SARS-CoV-2 based on MSD testing. Of note, antibody to the single SARS-CoV-2 RBD target was detected in 329/407 (81%) of 2013 sera and 91/488 (19%) of 2020 sera. Among the SARS-CoV-2 overall sero-negative population, age was correlated with anti-HCoV antibody levels and these, notably 229E and HKU1, were correlated with cross-reactive anti-SARS-CoV-2 RBD titres. SARS-CoV-2 overall sero-positive individuals showed higher titres to HCoV more generally. CONCLUSION: Most people have an HCoV priming exposure by 10 years of age and IgG levels are stable thereafter. Anti-HCoV antibodies can cross-react with SARS-CoV-2 epitopes. These immunological interactions warrant further investigation with respect to their implications for COVID-19 clinical outcomes.

背景：老年人在 SARS-CoV-2 大流行期间受到了不成比例的影响，包括患重病和长期 COVID-19 的风险更高。先前暴露于地方性人类冠状病毒（HCoV）可能会调节对 SARS-CoV-2 感染的反应，并导致与年龄相关的观察结果。我们假设，对 SARS-CoV-2 的交叉反应性抗体与 HCoV 抗体有关，并且两者都随年龄增长而增加。

方法：为了评估 SARS-CoV-2 未暴露个体，我们利用了在加拿大不列颠哥伦比亚省（BC）进行的存档匿名残留血清学调查，包括 SARS-CoV-2 出现之前（2013 年 5 月）和 BC 广泛社区传播之前（2020 年 5 月）。从≤10 至≥80 岁的个体中寻求了 50 份血清，每个 10 岁年龄组有 50 份血清，根据 2020 年 3 月和 9 月的血清进行补充。血清用 Meso Scale Diagnostics（MSD）电化学发光多重免疫分析法进行检测，以定量针对 HCoV 的 Spike 蛋白的 IgG 抗体，包括 alpha（HCoV-229E、HCoV-NL63）和 beta（HCoV-HKU1、HCoV-OC43）病毒以及 2003 年的β冠状病毒 SARS-CoV-1。同样测量了针对 Spike、Nucleocapsid 和 SARS-CoV-2 的受体结合域（RBD）的交叉反应性抗体，总体上 SARS-CoV-2 血清阳性定义为≥2 个目标呈阳性。

结果：样本包括 2013 年的 407 份血清，其中 17 份来自≤10 岁的儿童。2020 年的样本包括 488 份血清，其中 88 份来自≤10 岁的儿童。到 10 岁时，所有四种地方性 HCoV 的抗 Spike 抗体都已获得。在 2013 年的 407 份血清中有 20/407（5%），在 2020 年的 488 份血清中有 8/488（2%）被 MSD 检测认为是 SARS-CoV-2 血清阳性。值得注意的是，在 2013 年的 329/407（81%）和 2020 年的 91/488（19%）血清中检测到针对 SARS-CoV-2 单一 RBD 目标的抗体。在 SARS-CoV-2 总体血清阴性人群中，年龄与抗 HCoV 抗体水平相关，这些抗体水平，特别是 229E 和 HKU1，与交叉反应性抗 SARS-CoV-2 RBD 滴度相关。SARS-CoV-2 总体血清阳性个体表现出更高的针对 HCoV 的抗体滴度。

结论：大多数人在 10 岁之前就已经有了 HCoV 的初始暴露，并且此后 IgG 水平保持稳定。抗 HCoV 抗体可以与 SARS-CoV-2 表位发生交叉反应。这些免疫学相互作用值得进一步研究，以了解它们对 COVID-19 临床结果的影响。