(A) Percentage of TCR features with a statistically significant (false discovery rate [FDR] <0.01) association with a restricting HLA allele. We tested for associations between patients’ inferred genotype and TCR feature abundance using beta-binomial regression controlling for age, sex, and days since COVID-19 diagnosis. (B) For each clonotype/meta-clonotype, the percent of bulk repertoires from COVID-19 patients (n = 694) containing TCRs meeting the criteria defined by (1) EXACT (TCRs matching the centroid TRBV gene and amino acid sequence of the complementarity determining region [CDR]3), (2) RADIUS (TCR centroid with inclusion criteria defined by an optimized TCRdist radius), or (3) RADIUS + MOTIF (inclusion criteria defined by TCR centroid, optimized radius, and the CDR3 motif constraint). See Figure 1 and Methods for details. Meta-clonotype radii were engineered using synthesized backgrounds developed for each MIRA set. Each background contained 100,000 Optimized Likelihood estimate of Immunoglobulin Amino acid sequences (OLGA)-generated TCRs and 100,000 TCRs subsampled from umbilical cord blood; OLGA-generated TCRs were sampled to match to the V–J gene frequency in each MIRA receptor set (i.e., MIRA1, 10, 30, 44, 45, 48, 51, 53, 55, 70, 99, 110, 111,118, 133, 140, or 183) with weighting to account for the sampling bias (see Methods for details).