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Proteomics Investigation of Diverse Serological Patterns in COVID-19

By Xiao Liang, Rui Sun, Jing Wang, Kai Zhou, Jun Li, Shiyong Chen, Mengge Lyu, Sainan Li, Zhangzhi Xue, Yingqiu Shi, Yuting Xie, Qiushi Zhang, Xiao Yi, Juan Pan, Donglian Wang, Jiaqin Xu, Hongguo Zhu, Guangjun Zhu, Jiansheng Zhu, Yi Zhu, Yufen Zheng, Bo Shen, Tiannan Guo

Posted 22 Aug 2022
medRxiv DOI: 10.1101/2022.08.21.22278967

Serum antibodies IgM and IgG are elevated during COVID-19 to defend against viral attack. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their two-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense, and that high titers of IgM might not be favorable to COVID-19 recovery.

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