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体液 SARS-CoV-2 免疫应答与 COVID-19 康复者、接种疫苗者和未接种疫苗者的新冠后综合征相关。

Humoral SARS-CoV-2 Immune Response in COVID-19 Recovered Vaccinated and Unvaccinated Individuals Related to Post-COVID-Syndrome.

机构信息

Institute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, Theodor Kutzer Ufer 1-3, 68167 Mannheim, Germany.

Institute of Transfusion Medicine and Immunology, Heidelberg University, 68167 Mannheim, Germany.

出版信息

Viruses. 2023 Feb 6;15(2):454. doi: 10.3390/v15020454.

DOI:10.3390/v15020454
PMID:36851668
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9966735/
Abstract

BACKGROUND

The duration of anti-SARS-CoV-2-antibody detectability up to 12 months was examined in individuals after either single convalescence or convalescence and vaccination. Moreover, variables that might influence an anti-RBD/S1 antibody decline and the existence of a post-COVID-syndrome (PCS) were addressed.

METHODS

Forty-nine SARS-CoV-2-qRT-PCR-confirmed participants completed a 12-month examination of anti-SARS-CoV-2-antibody levels and PCS-associated long-term sequelae. Overall, 324 samples were collected. Cell-free DNA (cfDNA) was isolated and quantified from EDTA-plasma. As cfDNA is released into the bloodstream from dying cells, it might provide information on organ damage in the late recovery of COIVD-19. Therefore, we evaluated cfDNA concentrations as a biomarker for a PCS. In the context of antibody dynamics, a random forest-based logistic regression with antibody decline as the target was performed and internally validated.

RESULTS

The mean percentage dynamic related to the maximum measured value was 96 (±38)% for anti-RBD/S1 antibodies and 30 (±26)% for anti-N antibodies. Anti-RBD/S1 antibodies decreased in 37%, whereas anti-SARS-CoV-2-anti-N antibodies decreased in 86% of the subjects. Clinical anti-RBD/S1 antibody decline prediction models, including vascular and other diseases, were cross-validated (highest AUC 0.74). Long-term follow-up revealed no significant reduction in PCS prevalence but an increase in cognitive impairment, with no indication for cfDNA as a marker for a PCS.

CONCLUSION

Long-term anti-RBD/S1-antibody positivity was confirmed, and clinical parameters associated with declining titers were presented. A fulminant decrease in anti-SARS-CoV-2-anti-N antibodies was observed (mean change to maximum value 30 (±26)%). Anti-RBD/S1 antibody titers of SARS-CoV-2 recovered subjects boosted with a vaccine exceeded the maximum values measured after single infection by 235 ± 382-fold, with no influence on preexisting PCS. PCS long-term prevalence was 38.6%, with an increase in cognitive impairment compromising the quality of life. Quantified cfDNA measured in the early post-COVID-19 phase might not be an effective marker for PCS identification.

摘要

背景

本研究旨在探讨在单恢复期或恢复期加疫苗接种后,个体抗 SARS-CoV-2 抗体的持续时间是否可达 12 个月。此外,本研究还探讨了可能影响抗 RBD/S1 抗体下降和新冠后综合征(PCS)的变量。

方法

49 名经 SARS-CoV-2-qRT-PCR 确诊的参与者完成了为期 12 个月的抗 SARS-CoV-2 抗体水平和 PCS 相关长期后遗症检查。共采集了 324 份样本。从 EDTA 血浆中分离并定量提取无细胞 DNA(cfDNA)。由于 cfDNA 是从死亡细胞释放到血液中的,因此它可能为 COVID-19 晚期恢复中的器官损伤提供信息。因此,我们将 cfDNA 浓度作为 PCS 的生物标志物进行评估。在抗体动态变化方面,我们进行了基于随机森林的逻辑回归分析,以抗体下降为目标,并进行了内部验证。

结果

抗 RBD/S1 抗体的最大测量值与最大测量值相关的平均百分比动态为 96(±38)%,而抗-N 抗体为 30(±26)%。37%的受试者出现抗 RBD/S1 抗体下降,而 86%的受试者出现抗 SARS-CoV-2-抗-N 抗体下降。血管和其他疾病等临床抗 RBD/S1 抗体下降预测模型得到了交叉验证(最高 AUC 为 0.74)。长期随访发现,PCS 的流行率没有显著降低,但认知障碍增加,cfDNA 没有作为 PCS 的标志物。

结论

本研究证实了长期抗 RBD/S1 抗体阳性,并提出了与滴度下降相关的临床参数。观察到抗 SARS-CoV-2-抗-N 抗体的急剧下降(与最大测量值的平均变化为 30(±26)%)。接受 SARS-CoV-2 恢复期疫苗接种的恢复期患者的抗 RBD/S1 抗体滴度增加了 235±382 倍,超过了单次感染后的最高值,且对已有的 PCS 无影响。PCS 的长期流行率为 38.6%,认知障碍增加,降低了生活质量。在 COVID-19 早期阶段测量的定量 cfDNA 可能不是识别 PCS 的有效标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d690/9966735/ac8a9ba4a523/viruses-15-00454-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d690/9966735/ac8a9ba4a523/viruses-15-00454-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d690/9966735/ef0b54e3576f/viruses-15-00454-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d690/9966735/8ce30501b059/viruses-15-00454-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d690/9966735/dbb22d44c925/viruses-15-00454-g003.jpg
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