Single cell and immune repertoire profiling of COVID-19 patients reveal novel therapeutic candidates

COVID-19, a novel pneumonia caused by SARS-CoV-2, has rapidly become the largest threat to public health. Recent studies reported lymphocytopenia but also expansions of antigen-specific T/B cells during early-recovery stage. Here we investigated 16 early-recovery patients using scRNA-seq, HLA-genotyping and deep immune repertoire profling. Our analysis revealed 916 COVID-19-specific TCR groups enriched for a novel cytotoxic CD8+ phenotype with both resident memory (ZNF683+) and tissue exit (SIRP5) markers, and identified 114 statistically-confident virus epitopes. Further, we uncovered 374 BCR groups with somatic hypermutations and/or class switch recombinations. Molecular dynamics simulations revealed 15% of the highly expanded groups may serve as neutralizing antibodies against the virus Spike protein. Finally, we discovered that bacterial infection in COVID-19 patients may elevate monocytic myeloidderived suppressor cells via TLR4/NF!B signaling and cause disease aggravation. Together, we expect our findings and immune-receptor datasets to provide immediate therapeutic options against the pandemic of COVID-19.