Department of Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary, and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom.
Ear Nose and Throat Department, Alder Hey Children's Hospital, Liverpool, United Kingdom.
J Infect Dis. 2021 Oct 28;224(8):1305-1315. doi: 10.1093/infdis/jiab333.
BACKGROUND: A notable feature of coronavirus disease 2019 (COVID-19) is that children are less susceptible to severe disease. Children are known to experience more infections with endemic human coronaviruses (HCoVs) compared to adults. Little is known whether HCoV infections lead to cross-reactive anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. METHODS: We investigated the presence of cross-reactive anti-SARS-CoV-2 IgG antibodies to spike 1 (S1), S1-receptor-binding domain (S1-RBD), and nucleocapsid protein (NP) by enzyme-linked immunosorbent assays, and neutralizing activity by a SARS-CoV-2 pseudotyped virus neutralization assay, in prepandemic sera collected from children (n = 50) and adults (n = 45), and compared with serum samples from convalescent COVID-19 patients (n = 16). RESULTS: A significant proportion of children (up to 40%) had detectable cross-reactive antibodies to SARS-CoV-2 S1, S1-RBD, and NP antigens, and the anti-S1 and anti-S1-RBD antibody levels correlated with anti-HCoV-HKU1 and anti-HCoV-OC43 S1 antibody titers in prepandemic samples (P < .001). There were marked increases of anti-HCoV-HKU1 and - OC43 S1 (but not anti-NL63 and -229E S1-RBD) antibody titers in serum samples from convalescent COVID-19 patients (P < .001), indicating an activation of cross-reactive immunological memory to β-coronavirus spike. CONCLUSIONS: We demonstrated cross-reactive anti-SARS-CoV-2 antibodies in prepandemic serum samples from children and young adults. Promoting this cross-reactive immunity and memory response derived from common HCoV may be an effective strategy against SARS-COV-2 and future novel coronaviruses.
背景：2019 年冠状病毒病（COVID-19）的一个显著特征是儿童不易患重病。与成年人相比，儿童已知更容易感染地方性人类冠状病毒（HCoV）。目前尚不清楚 HCoV 感染是否会导致交叉反应性抗严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）抗体。
方法：我们通过酶联免疫吸附试验（ELISA）检测了流行前儿童（n=50）和成人（n=45）血清中针对刺突 1（S1）、S1-受体结合域（S1-RBD）和核衣壳蛋白（NP）的交叉反应性抗 SARS-CoV-2 IgG 抗体，并通过 SARS-CoV-2 假型病毒中和试验检测了中和活性，同时将血清样本与恢复期 COVID-19 患者（n=16）的血清样本进行比较。
结果：相当一部分儿童（高达 40%）可检测到针对 SARS-CoV-2 S1、S1-RBD 和 NP 抗原的交叉反应性抗体，并且流行前样本中抗 S1 和抗 S1-RBD 抗体水平与抗 HCoV-HKU1 和抗 HCoV-OC43 S1 抗体滴度相关（P<.001）。在恢复期 COVID-19 患者的血清样本中，抗 HCoV-HKU1 和 -OC43 S1 （但不抗 NL63 和 -229E S1-RBD）抗体滴度显著增加（P<.001），表明对β冠状病毒刺突的交叉反应性免疫记忆被激活。
结论：我们在流行前儿童和年轻成人血清样本中检测到了交叉反应性抗 SARS-CoV-2 抗体。促进这种源自常见 HCoV 的交叉反应性免疫和记忆反应可能是对抗 SARS-CoV-2 和未来新型冠状病毒的有效策略。
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