A compromised specific humoral immune response against the SARS-CoV-2 receptor-binding domain is related to viral persistence and periodic shedding in the gastrointestinal tract

作者：Fengyu Hu, Fengjuan Chen, Zhihua Ou, Qinghong Fan, Xinghua Tan, Yaping Wang, Yuejun Pan, Bixia Ke, Linghua Li, Yujuan Guan, Xiaoneng Mo, Jian Wang, Jinlin Wang, Chun Luo, Xueliang Wen, Min Li, Peidi Ren, Changwen Ke, Junhua Li, Chunliang Lei, Xiaoping Tang, Feng Li · 发表于：Cellular and Molecular Immunology · 年份：2020 · DOI：10.1038/s41423-020-00550-2 · 被引用次数：90 · 研究领域：SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies、SARS-CoV-2 detection and testing

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been redetected after discharge in some coronavirus disease 2019 (COVID-19) patients. The reason for the recurrent positivity of the test and the potential public health concern due to this occurrence are still unknown. Here, we analyzed the viral data and clinical manifestations of 289 domestic Chinese COVID-19 patients and found that 21 individuals (7.3%) were readmitted for hospitalization after detection of SARS-CoV-2 after discharge. First, we experimentally confirmed that the virus was involved in the initial infection and was not a secondary infection. In positive retests, the virus was usually found in anal samples (15 of 21, 71.4%). Through analysis of the intracellular viral subgenomic messenger RNA (sgmRNA), we verified that positive retest patients had active viral replication in their gastrointestinal tracts (3 of 16 patients, 18.7%) but not in their respiratory tracts. Then, we found that viral persistence was not associated with high viral titers, delayed viral clearance, old age, or more severe clinical symptoms during the first hospitalization. In contrast, viral rebound was associated with significantly lower levels of and slower generation of viral receptor-binding domain (RBD)-specific IgA and IgG antibodies. Our study demonstrated that the positive retest patients failed to create a robust protective humoral immune response, which might result in SARS-CoV-2 persistence in the gastrointestina...