Pathogen Genomics, Phenotype, and Immunity Program, Medical Research Council, Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe, Uganda.
Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda.
Front Immunol. 2023 Mar 16;14:1152522. doi: 10.3389/fimmu.2023.1152522. eCollection 2023.
Understanding how spike (S)-, nucleoprotein (N)-, and RBD-directed antibody responses evolved in mild and asymptomatic COVID-19 in Africa and their interactions with SARS-CoV-2 might inform development of targeted treatments and vaccines.
Here, we used a validated indirect in-house ELISA to characterise development and persistence of S- and N-directed IgG, IgM, and IgA antibody responses for 2430 SARS-CoV-2 rt-PCR-diagnosed Ugandan specimens from 320 mild and asymptomatic COVID-19 cases, 50 uninfected contacts, and 54 uninfected non-contacts collected weekly for one month, then monthly for 28 months.
During acute infection, asymptomatic patients mounted a faster and more robust spike-directed IgG, IgM, and IgA response than those with mild symptoms (Wilcoxon rank test, p-values 0.046, 0.053, and 0.057); this was more pronounced in males than females. Spike IgG antibodies peaked between 25 and 37 days (86.46; IQR 29.47-242.56 BAU/ml), were significantly higher and more durable than N- and RBD IgG antibodies and lasted for 28 months. Anti-spike seroconversion rates consistently exceeded RBD and nucleoprotein rates. Spike- and RBD-directed IgG antibodies were positively correlated until 14 months (Spearman's rank correlation test, p-values 0.0001 to 0.05), although RBD diminished faster. Significant anti-spike immunity persisted without RBD. 64% and 59% of PCR-negative, non-infected non-contacts and suspects, exhibited baseline SARS-CoV-2 N-IgM serological cross-reactivity, suggesting undetected exposure or abortive infection. N-IgG levels waned after 787 days, while N-IgM levels remained undetectable throughout.
Lower N-IgG seroconversion rates and the absence of N-IgM indicate that these markers substantially underestimate the prior exposure rates. Our findings provide insights into the development of S-directed antibody responses in mild and asymptomatic infections, with varying degrees of symptoms eliciting distinct immune responses, suggesting distinct pathogenic pathways. These longer-lasting data inform vaccine design, boosting strategies, and surveillance efforts in this and comparable settings.
了解刺突（S）-、核蛋白（N）-和受体结合域（RBD）导向的抗体反应在非洲轻度和无症状 COVID-19 中的演变及其与 SARS-CoV-2 的相互作用，可能有助于开发针对这些疾病的靶向治疗和疫苗。
在这里，我们使用经过验证的间接内部酶联免疫吸附试验（ELISA），对 320 例轻度和无症状 COVID-19 病例、50 名未感染的接触者和 54 名未感染的非接触者的 2430 份 SARS-CoV-2 逆转录酶聚合酶链反应（RT-PCR）诊断的乌干达样本中的 S-和 N-定向 IgG、IgM 和 IgA 抗体反应的发展和持续时间进行了特征描述，这些样本每周收集一次，持续一个月，然后每月收集一次，共 28 个月。
在急性感染期间，无症状患者比有轻度症状的患者更快、更强烈地产生刺突定向 IgG、IgM 和 IgA 反应（Wilcoxon 秩检验，p 值分别为 0.046、0.053 和 0.057）；这种情况在男性中比女性更为明显。刺突 IgG 抗体在 25 至 37 天达到峰值（86.46；IQR 29.47-242.56 BAU/ml），显著高于 N 和 RBD IgG 抗体，并且持续 28 个月。抗刺突血清转换率始终超过 RBD 和核蛋白率。刺突和 RBD 定向 IgG 抗体在 14 个月前呈正相关（Spearman 秩相关检验，p 值为 0.0001 至 0.05），尽管 RBD 衰减更快。尽管没有 RBD，但仍存在显著的抗刺突免疫。64%和 59%的 PCR 阴性、非感染的非接触者和疑似病例表现出 SARS-CoV-2 N-IgM 血清学交叉反应性，提示存在未被检测到的暴露或流产感染。N-IgG 水平在 787 天后下降，而 N-IgM 水平在整个过程中均无法检测到。
较低的 N-IgG 血清转化率和缺乏 N-IgM 表明这些标志物大大低估了先前的暴露率。我们的发现为轻度和无症状感染中 S 定向抗体反应的发展提供了深入了解，不同程度的症状引发了不同的免疫反应，表明存在不同的发病途径。这些持续时间更长的数据为疫苗设计、加强策略和在这种和类似环境中的监测工作提供了信息。
