Endogenously Produced SARS-CoV-2 Specific IgG Antibodies May Have a Limited Impact on Clearing Nasal Shedding of Virus during Primary Infection in Humans.
Endogenously Produced SARS-CoV-2 Specific IgG Antibodies May Have a Limited Impact on Clearing Nasal Shedding of Virus during Primary Infection in Humans.
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DOI：
10.3390/v13030516
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发表时间：
2021-03-20
期刊：
影响因子：
--
通讯作者：
Goyal A
中科院分区：
文献类型：
--
作者：
Yang S;Jerome KR;Greninger AL;Schiffer JT;Goyal A
虽然SARS-CoV-2特异性中和抗体已被开发用于治疗目的，但驱动SARS-CoV-2特异性IgG和IgM抗体产生的特异性病毒触发物仍仅部分表征。此外，尚不清楚内源性抗体是否驱动病毒清除，这可能导致自然感染期间临床严重程度的减轻。我们开发了一系列非线性数学模型来研究SARS-CoV-2病毒和抗体动力学是否耦合或由单独的过程控制。重症患者IgG抗体产生率较高，但IgM抗体无明显变化。这两种同种型的最大水平取决于它们的生产率，而不是人与人之间的不同饱和度。我们的研究结果表明，IgG水平的指数激增发生在症状发作后约5-10天，不需要持续的抗原刺激。SARS-CoV-2特异性IgG抗体似乎对病毒动力学的影响有限或没有影响，但可能在初次感染后期增强病毒清除，这是由于抗体与病毒的结合作用，而不是中和作用。总之，SARS-CoV-2特异性IgG抗体在清除鼻道感染方面可能仅发挥有限的作用，尽管在接种疫苗后或先前感染后提供了针对感染的长期免疫力。
While SARS-CoV-2 specific neutralizing antibodies have been developed for therapeutic purposes, the specific viral triggers that drive the generation of SARS-CoV-2 specific IgG and IgM antibodies remain only partially characterized. Moreover, it is unknown whether endogenously derived antibodies drive viral clearance that might result in mitigation of clinical severity during natural infection. We developed a series of non-linear mathematical models to investigate whether SARS-CoV-2 viral and antibody kinetics are coupled or governed by separate processes. Patients with severe disease had a higher production rate of IgG but not IgM antibodies. Maximal levels of both isotypes were governed by their production rate rather than different saturation levels between people. Our results suggest that an exponential surge in IgG levels occurs approximately 5–10 days after symptom onset with no requirement for continual antigenic stimulation. SARS-CoV-2 specific IgG antibodies appear to have limited to no effect on viral dynamics but may enhance viral clearance late during primary infection resulting from the binding effect of antibody to virus, rather than neutralization. In conclusion, SARS-CoV-2 specific IgG antibodies may play only a limited role in clearing infection from the nasal passages despite providing long-term immunity against infection following vaccination or prior infection.
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DOI：
10.1056/nejmoa2029849
发表时间：
2021-01-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chen P;Nirula A;Heller B;Gottlieb RL;Boscia J;Morris J;Huhn G;Cardona J;Mocherla B;Stosor V;Shawa I;Adams AC;Van Naarden J;Custer KL;Shen L;Durante M;Oakley G;Schade AE;Sabo J;Patel DR;Klekotka P;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
抗病毒疗法的效力和时机是SARS-COV-2脱落持续时间的决定因素和炎症反应的强度。
影响因子：
13.6
作者：
Goyal A;Cardozo-Ojeda EF;Schiffer JT
通讯作者：
Schiffer JT
影响因子：
9.4
作者：
Addetia A;Crawford KHD;Dingens A;Zhu H;Roychoudhury P;Huang ML;Jerome KR;Bloom JD;Greninger AL
通讯作者：
Greninger AL
影响因子：
6.4
作者：
Cai, Xue-fei;Chen, Juan;Wang, De-qiang
通讯作者：
Wang, De-qiang
SARS-COV-2 mRNA疫苗促进与中和抗体产生相关的有效抗原特异性生发中心反应。
影响因子：
32.4
作者：
Lederer K;Castaño D;Gómez Atria D;Oguin TH 3rd;Wang S;Manzoni TB;Muramatsu H;Hogan MJ;Amanat F;Cherubin P;Lundgreen KA;Tam YK;Fan SHY;Eisenlohr LC;Maillard I;Weissman D;Bates P;Krammer F;Sempowski GD;Pardi N;Locci M
通讯作者：
Locci M