Rapid and efficacious humoral responses are required for recovery from hemorrhagic fever with renal syndrome

Hemorrhagic fever with renal syndrome (HFRS) caused by hantaan virus (HTNV) infection displays variable clinical signs. Humoral responses are important players against HTNV infections, however, this process is poorly understood. Herein, we investigated the phenotype, temporal dynamics, and characteristics of B-cell receptor repertoire (BCR) in a patient cohort with HFRS. The serological profile was characterized by low expression level of NP-specific antibody in severe cases. Importantly, B-cell subsets were activated and proliferated within the first two weeks of symptom onset, and the moderate cases reacted more rapidly. BCR analysis in the recovery phase revealed immunoglobulin gene diversity had dramatical rise and progressed more significant in the moderate group. The transcription of gene sets related to B-cell was lower, but the inflammatory sets were over-activated in severe cases. These data suggested the clinical signs and diseases recovery in HFRS patients were benefitted from rapid and efficacious humoral responses. Clinical specimens were collected from HFRS patients at Baoji central hospital from November 2018 to January 2019. NP-IgM and NP-IgG in serum specimens were detected by serological testing for HTNV diagnosis. According to the diagnostic criteria from the prevention and treatment strategy of HFRS promulgated by the Ministry of Health, People’s Republic of China, the patients were classified into four clinical types: mild, moderate, severe, and critical (Ma et al., 2015). To depict the dynamic changes of humoral response, the consecutive blood samples of HTNV patients with difference clinical types were collected.