Hua Qiaoli, Zhang Peng, Qin Shengle, Feng Bing, Xiao Bin, Zheng Guangjuan, Ye Taoyu, Zheng Danwen, Mo Jiayi, Liu Yuntao, Cai Yun, Xu Xiaohua, Hu Ji, Ding Banghan, Li Yingrui, Guo Jianwen, Wang Jun, Cao Hongzhi, Zhang Zhongde
Department of Clinical Laboratory, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.
iCarbonX (Zhuhai) Company Limited, Zhuhai, China.
Front Med (Lausanne). 2025 Aug 11;12:1623509. doi: 10.3389/fmed.2025.1623509. eCollection 2025.
Long-term SARS-CoV-2-IgG antibody durability after natural infection remains a critical determinant of long-term protection. However, the factors that affect long-term IgG antibody durability are not fully understood.
This study delves into the clinical and host genetic factors influencing the level of long-term anti-SARS-CoV-2-receptor-binding domain IgG (RBD-IgG) antibodies after natural infection during the first wave of the COVID-19 pandemic (17 January to 24 June 2020). The cohort, comprising 572 COVID-19 patients from Wuhan, China, had no exposure to COVID-19 vaccines, variants, or antiviral treatments, enabling a focused analysis of the virus's direct impact.
We found that the rate of RBD-IgG seropositivity 6 months after infection remained high (94.58%). Through a generalized linear model and mediation analysis, older age, independent of disease severity, was found to be a key independent factor associated with higher post-infection RBD-IgG titers. Hypothesis-generating analyses through a genome-wide association study revealed that rs117929853 ( = 3.6 × 10), a variant located upstream of the , was significantly associated with RBD-IgG persistence, suggesting a potential mechanistic link between polymorphisms and sustained humoral immunity.
The study underscores the significant role of age and genetic factors in the pathogenesis of sustained humoral immunity, which requires further validation.
自然感染后严重急性呼吸综合征冠状病毒2（SARS-CoV-2）IgG抗体的长期耐久性仍然是长期保护的关键决定因素。然而，影响IgG抗体长期耐久性的因素尚未完全明确。
本研究深入探讨了在2019冠状病毒病（COVID-19）大流行第一波期间（2020年1月17日至6月24日）自然感染后影响长期抗SARS-CoV-2受体结合域IgG（RBD-IgG）抗体水平的临床和宿主遗传因素。该队列由来自中国武汉的572例COVID-19患者组成，未接触过COVID-19疫苗、变异株或抗病毒治疗，从而能够重点分析病毒的直接影响。
我们发现感染后6个月RBD-IgG血清阳性率仍然很高（94.58%）。通过广义线性模型和中介分析，发现年龄较大是与感染后RBD-IgG滴度较高相关的关键独立因素，与疾病严重程度无关。通过全基因组关联研究进行的假设生成分析显示，位于基因上游的rs117929853（=3.6×10）与RBD-IgG的持久性显著相关，提示基因多态性与持续体液免疫之间可能存在机制联系。
该研究强调了年龄和遗传因素在持续体液免疫发病机制中的重要作用，这需要进一步验证。
