Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients.

Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients.
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人类抗体对SARS-COV-2峰值蛋白的受体结合结构域的持久性和衰减在COVID-19患者中。

DOI:
10.1126/sciimmunol.abe0367
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发表时间:
2020-10-08
期刊:
影响因子:
24.8
通讯作者:
Charles RC
Charles RC
中科院分区:
医学1区
文献类型:
--
作者:
Iyer AS;Jones FK;Nodoushani A;Kelly M;Becker M;Slater D;Mills R;Teng E;Kamruzzaman M;Garcia-Beltran WF;Astudillo M;Yang D;Miller TE;Oliver E;Fischinger S;Atyeo C;Iafrate AJ;Calderwood SB;Lauer SA;Yu J;Li Z;Feldman J;Hauser BM;Caradonna TM;Branda JA;Turbett SE;LaRocque RC;Mellon G;Barouch DH;Schmidt AG;Azman AS;Alter G;Ryan ET;Harris JB;Charles RC

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重症COVID患者对SARS-CoV-2 RBD的IgM和IgA应答迅速衰减,而IgG应答持续3个月以上。我们测量了343名北美SARS-CoV-2感染患者(其中93%需要住院治疗)在症状发作后122天内对SARS-CoV-2刺突(S)蛋白受体结合结构域(RBD)的血浆和/或血清抗体反应,并将其与1548名在大流行前获得血液样本的个体的反应进行了比较。在设定了完全特异性(100%)的血清阳性阈值后,我们估计在症状发作后15至28天内检测感染个体的IgG、IgA和IgM的灵敏度分别为95%、90%和81%。虽然所有三种同种型的血清转换的中位时间接近12天,但针对RBD的IgA和IgM抗体是短暂的,症状发作后血清转换的中位时间为71天和49天。相比之下,抗RBD IgG应答在90天内缓慢衰减,仅3个血清阳性个体在此时间段内血清逆转。SARS-CoV-2 RBD的IgG抗体与抗S中和抗体滴度密切相关,后者在症状发作后75天内几乎没有下降。我们观察到SARS-CoV-2 RBD靶向抗体与其他广泛传播的冠状病毒(HKU 1,229 E,OC 43,NL 63)没有交叉反应性。这些数据表明,RBD靶向抗体是以前和最近感染的极好标志物,差异同种型测量可以帮助区分最近和较旧的感染,IgG反应在感染后的前几个月持续存在,并且与中和抗体高度相关。
IgM and IgA responses to SARS-CoV-2 RBD in severe COVID patients decay rapidly, while IgG responses persist for over 3 months. We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds for perfect specificity (100%), we estimated sensitivities of 95% for IgG, 90% for IgA, and 81% for IgM for detecting infected individuals between 15 and 28 days after symptom onset. While the median time to seroconversion was nearly 12 days across all three isotypes tested, IgA and IgM antibodies against RBD were short-lived with median times to seroreversion of 71 and 49 days after symptom onset. In contrast, anti-RBD IgG responses decayed slowly through 90 days with only 3 seropositive individuals seroreverting within this time period. IgG antibodies to SARS-CoV-2 RBD were strongly correlated with anti-S neutralizing antibody titers, which demonstrated little to no decrease over 75 days since symptom onset. We observed no cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies with other widely circulating coronaviruses (HKU1, 229 E, OC43, NL63). These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.
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