COVID-19 relapse associated with SARS-CoV-2 evasion from CD4+ T-cell recognition in an agammaglobulinemia patient

A 25-year-old patient with a primary immunodeficiency lacking immunoglobulin production experienced a relapse after a 239-day period of persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Viral genetic sequencing demonstrated that SARS-CoV-2 had evolved during the infection period, with at least five mutations associated with host cellular immune recognition. Among them, the T32I mutation in ORF3a was found to evade recognition by CD4+ T cells. The virus found after relapse showed an increased proliferative capacity in vitro. SARS-CoV-2 may have evolved to evade recognition by CD4+ T cells and increased in its proliferative capacity during the persistent infection, likely leading to relapse. These mutations may further affect viral clearance in hosts with similar types of human leukocyte antigens. The early elimination of SARS-CoV-2 in immunocompromised patients is therefore important not only to improve the condition of patients but also to prevent the emergence of mutants that threaten public health. [Display omitted] •SARS-CoV-2 persistently infected a man with humoral immunodeficiency for 239 days•COVID-19 relapsed and SARS-CoV-2 evolved during the infection period•The virus isolated after relapse had an increased proliferative capacity in vitro•SARS-CoV-2 may have evolved to evade recognition by CD4+ T-cells Immunology