Investigation of SARS-CoV-2 variants that escape from cellular immunity in the absence of humoral immunity

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency causing a lack of immunoglobulin production. A COVID-19 patient with XLA showed persistent infection for more than 239 days, representing the longest duration yet reported, in whom SARS-CoV-2 evolved increased proliferative capacity. We identify a mutation of SARS-CoV-2 that is responsible for the immune escape from the cellular immunity of this patient, as well as the TCR that could recognize the wild type antigen but not the correspoinding mutant antigen. Overall design: We stimulated the PBMC from the donor with SARS-CoV-2 peptides that cover the mutation identified from the patient for 12 days, sorted the T cells and analyzed the cells by single-cell TCR and RNA sequencing. We reconstituted a highly expanded TCR into a reporter cell line, and identified its epitope.