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

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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2023-05-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004223007629
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author 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
author_facet 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
author_sort Ryo Morita
collection DOAJ
description 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.
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spelling doaj.art-f0e08f94d7854578b413062f38f959922023-05-02T04:05:13ZengElsevieriScience2589-00422023-05-01265106685COVID-19 relapse associated with SARS-CoV-2 evasion from CD4+ T-cell recognition in an agammaglobulinemia patientRyo Morita0Ritsuko Kubota-Koketsu1Xiuyuan Lu2Tadahiro Sasaki3Emi E. Nakayama4Yu-chen Liu5Daisuke Okuzaki6Daisuke Motooka7James Badger Wing8Yasunori Fujikawa9Yuji Ichida10Kiyoko Amo11Tetsushi Goto12Junichi Hara13Michinori Shirano14Sho Yamasaki15Tatsuo Shioda16Department 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, JapanDepartment of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, JapanLaboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, JapanDepartment of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, JapanDepartment of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, JapanLaboratory of Human Immunology (Single Cell Genomics), Immunology Frontier Research Center, Osaka University, Osaka 565-0871, JapanLaboratory of Human Immunology (Single Cell Genomics), Immunology Frontier Research Center, Osaka University, Osaka 565-0871, JapanDepartment of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, JapanLaboratory of Human Immunology (Single Cell Immunology), Immunology Frontier Research Center, Osaka University, Osaka 565-0871, JapanDepartment of Medical Laboratory, Osaka City General Hospital, Osaka 534-0021, JapanDepartment of Pharmacy, Osaka City General Hospital, Osaka 534-0021, JapanDepartment of Pediatric Emergency Medicine, Osaka City General Hospital, Osaka 534-0021, JapanDepartment of Infectious Diseases, Osaka City General Hospital, Osaka 534-0021, JapanDepartment of Pediatric Hematology and Oncology, Osaka City General Hospital, Osaka 534-0021, JapanDepartment of Infectious Diseases, Osaka City General Hospital, Osaka 534-0021, Japan; Corresponding authorLaboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; Corresponding authorDepartment of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223007629Immunology
spellingShingle 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
COVID-19 relapse associated with SARS-CoV-2 evasion from CD4+ T-cell recognition in an agammaglobulinemia patient
iScience
Immunology
title COVID-19 relapse associated with SARS-CoV-2 evasion from CD4+ T-cell recognition in an agammaglobulinemia patient
title_full COVID-19 relapse associated with SARS-CoV-2 evasion from CD4+ T-cell recognition in an agammaglobulinemia patient
title_fullStr COVID-19 relapse associated with SARS-CoV-2 evasion from CD4+ T-cell recognition in an agammaglobulinemia patient
title_full_unstemmed COVID-19 relapse associated with SARS-CoV-2 evasion from CD4+ T-cell recognition in an agammaglobulinemia patient
title_short COVID-19 relapse associated with SARS-CoV-2 evasion from CD4+ T-cell recognition in an agammaglobulinemia patient
title_sort covid 19 relapse associated with sars cov 2 evasion from cd4 t cell recognition in an agammaglobulinemia patient
topic Immunology
url http://www.sciencedirect.com/science/article/pii/S2589004223007629
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