Novel skewed usage of B-cell receptors in COVID-19 patients with various clinical presentations.

B cell-mediated immune responses play important roles in controlling SARS-CoV infection. Here, we performed the single-cell B cell receptor sequencing (scBCR-seq) of the PBMC samples from eleven healthy controls, five asymptomatic subjects and 33 symptomatic COVID-19 patients with various clinical presentations, and subsequently analyzed the abundance and diversity of the BCR repertoires in different groups, respectively. We revealed the skewed usage of the IGHV, IGLV and IGKV genes and identified a number of heavy or light chain VDJ gene pairs and combinational preference in each group, such as IGKV3-7 and IGKV2-24 enriched in the asymptomatic subjects, whereas IGHV3-13, IGHV3-23-IGHJ4, IGHV1-18-IGLV3-19, IGHV1-18-IGLV3-21, and IGHV1-18-IGLV3-25 enriched in the recovery patients with severe diseases. We also observed the differential expression of IGHV3-23 in various B cell clusters by analysis of the scRNA-seq data. Additional dock analysis indicated that IGHV3-13 could bind to the spike protein of SARS-CoV-2. These findings may advance our understanding of the humoral immune responses in COVID-19 patients and help develop novel vaccine candidates as well as therapeutical antibodies against SASR-CoV-2 infections.