Persistence of SARS-CoV-2-IgG Antibody Durability in convalescent COVID-19 patients 6 months after the natural infection

Qiaoli Hua¹Peng Zhang²Shengle Qin³Bing Feng⁴Bin Xiao²Guangjuan Zheng⁵Taoyu Ye²Danwen Zheng⁶Jiayi Mo²Yuntao Liu⁶Yun Cai²Xiaohua Xu⁶Ji Hu²Banghan Ding⁶Yingrui Li²Jianwen Guo⁶Jun Wang²Hongzhi Cao²Zhongde Zhang^6,7,8*

• ¹Department of Clinical Laboratory, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, 518033, China, Shenzhen, China
• ²iCarbonX (Zhuhai) Company Limited, Shenzhen, China
• ³The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China
• ⁴Department of Pharmacology of Traditional Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
• ⁵Department of Pharmacology of Traditional Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine,, Guangzhou, China
• ⁶Department of Emergency, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China., Guangzhou, China
• ⁷Guangdong Provincial Key Laboratory of Research on Emergency in TCM, Guangzhou, China, Guangzhou, China
• ⁸State Key Laboratory of Dampness Syndrome of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China., Guangzhou, China

Long-term SARS-CoV-2-IgG antibody durability after the 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 (January 17 to June 24, 2020). The cohort, comprising 572 COVID-19 patients from Wuhan, China, was devoid of 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 (P=3.6 × 10 ⁻ ⁸ ), a variant located upstream of the xanthine dehydrogenase gene (XDH), was significantly associated with RBD-IgG persistence, suggesting a potential mechanistic link between XDH 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.