COVID-19 relapse associated with SARS-CoV-2 evasion from CD4+ T-cell recognition in an agammaglobulinemia patient
Ryo Morita,
Ritsuko Kubota-Koketsu,
Xiuyuan Lu,
Tadahiro Sasaki,
Emi E. Nakayama,
Yu-chen Liu,
Daisuke Okuzaki,
Daisuke Motooka,
James Badger Wing,
Yasunori Fujikawa,
Yuji Ichida,
Kiyoko Amo,
Tetsushi Goto,
Junichi Hara,
Michinori Shirano,
Sho Yamasaki,
Tatsuo Shioda
Affiliations
Ryo Morita
Department of Infectious Diseases, Osaka City General Hospital, Osaka 534-0021, Japan; Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Ritsuko Kubota-Koketsu
Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Xiuyuan Lu
Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
Tadahiro Sasaki
Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Emi E. Nakayama
Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Yu-chen Liu
Laboratory of Human Immunology (Single Cell Genomics), Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
Daisuke Okuzaki
Laboratory of Human Immunology (Single Cell Genomics), Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
Daisuke Motooka
Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
James Badger Wing
Laboratory of Human Immunology (Single Cell Immunology), Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
Yasunori Fujikawa
Department of Medical Laboratory, Osaka City General Hospital, Osaka 534-0021, Japan
Yuji Ichida
Department of Pharmacy, Osaka City General Hospital, Osaka 534-0021, Japan
Kiyoko Amo
Department of Pediatric Emergency Medicine, Osaka City General Hospital, Osaka 534-0021, Japan
Tetsushi Goto
Department of Infectious Diseases, Osaka City General Hospital, Osaka 534-0021, Japan
Junichi Hara
Department of Pediatric Hematology and Oncology, Osaka City General Hospital, Osaka 534-0021, Japan
Michinori Shirano
Department of Infectious Diseases, Osaka City General Hospital, Osaka 534-0021, Japan; Corresponding author
Sho Yamasaki
Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; Corresponding author
Tatsuo Shioda
Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Corresponding author
Summary: 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.
