Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is an ongoing pandemic that continues to evolve and reinfect individuals. To understand the convergent antibody responses that evolved over the course of the pandemic, we evaluated the immunoglobulin repertoire of individuals infected by different SARS-CoV-2 variants for similarity between patients. We utilized four public RNA-seq data sets collected between March 2020 and March 2022 from the Gene Expression Omnibus (GEO) in our longitudinal analysis. This covered individuals infected with Alpha and Omicron variants. In total, from 269 SARS-CoV-2-positive patients and 26 negative patients, 629,133 immunoglobulin heavy-chain variable region V(D)J sequences were reconstructed from sequencing data. We grouped samples based on the SARS-CoV-2 variant type and/or the time they were collected from patients. Our comparison of patients within each SARS-CoV-2-positive group found 1011 common V(D)Js (same V gene, J gene and CDR3 amino acid sequence) shared by more than one patient and no common V(D)Js in the noninfected group. Taking convergence into account, we clustered based on similar CDR3 sequence and identified 129 convergent clusters from the SARS-CoV-2-positive groups. Within the top 15 clusters, 4 contain known anti-SARS-CoV-2 immunoglobulin sequences with 1 cluster confirmed to cross-neutralize variants from Alpha to Omicron. In our analysis of longitudinal groups that include Alpha and Omicron variants, we find that 2.7% of the common CDR3s found within groups were also present in more than one group. Our analysis reveals common and convergent antibodies, which include anti-SARS-CoV-2 antibodies, in patient groups over various stages of the pandemic.

The severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has infected over 600 million individuals and caused over 6.5 million deaths. To understand the immune response individuals have from the SARS-CoV-2 infection, we studied the immunoglobulins against the virus’s antigens. The diversified complementarity determining region 3 (CDR3) can be used to characterize an antibody. We downloaded four public RNA-seq data sets that were collected be-tween March 2020 and March 2022 from the Gene Expression Omnibus (GEO) in our longitudinal analysis. In total, there were 269 SARS-CoV-2 positive patients and 26 negative patients who served as a control group. Samples were grouped based on their SARS-CoV-2 variant type and/or the time they were collected. Among 629,137 immunoglobulin V(D)J sequences identified by reconstructing the V(D)J sequences, we found 1011 common V(D)Js (same V gene, J gene and CDR3 sequences in each SARS-CoV-2 positive group) shared by more than one patient in each group and no common V(D)Js were from the negative control group. In our clustering analysis, we identified 129 convergent clusters from the SARS-CoV-2 positive groups. One of these convergent clusters matched the protein sequence of crystal 3D structures of the antibodies against SARS-CoV-2 in the Protein Data Bank (PDB). In our longitudinal analysis between the Alpha and Omicron variant, we found 2.7% of common CDR3s were shared although the longitudinal profiling of common V(D)Js was variant specific. Although diverse immunoglobulin profiles were observed, the convergence of common V(D)Js suggests that there exists antibodies with similar antigenic specificities across patients in different groups over various stages of the pandemic.