Figure 1. Roadmap for analysis of BCR repertoires.

Top: We collected bulk blood IgG BCR samples from three healthy individuals and 19 COVID-19 patients where two patients had mild symptoms, 12 had moderate symptoms, and five had severe symptoms (different markers and colors); see Methods. We also collected CD38⁺ plasma B-cells from PBMC samples of seven patients in this cohort (six moderate, one severe) and from seven additional patients (two asymptomatic, three mild, two moderate), and three healthy individuals (Fig. S2, Tables S1, S2). Samples were collected at different time points during infection (shown in center for bulk repertoires). We distinguished between productive receptors and unproductive receptors that had frameshifts due to V(D)J recombination. Line segments of varying lengths represent full V(D)J rearrangements (colors). In each patient, we constructed clonal lineages for productive and unproductive BCRs and inferred the naïve progenitor of the lineage (Methods). Bottom: 1. Using the set of unproductive inferred naïve BCRs, we inferred a model to characterize the null probability for generation of receptors P_gen(σ)(Marcou et al., 2018). We inferred a selection model (Sethna et al. 2020) to characterize the deviation from the null among inferred naïve productive BCRs, with the probability of entry to the periphery P_gen(σ) and selection factors q_f(σ), dependent on receptor sequence features. 2. Based on temporal information of sampled BCRs, we identified clonal lineages that showed significant expansion during infection. 3. We identified progenitors of clonal lineages shared among individuals and assessed the significance of these sharing statistics based on the probabilities to find each receptor in the periphery. The shared expanding clonal lineages that contain plasma B-cells, are likely candidates for secreting responsive antibodies during infection. We verified reactivity of receptors to SARS-CoV-2 antigenic epitopes using sorted single-cell data. We also identified previously characterized monoclonal antibodies (mAbs) specific to SARS-CoV-2 and SARS-CoV-1.