Frontiers in Immunology (Dec 2024)

A comprehensive immune repertoire signature distinguishes pulmonary infiltration in SARS-CoV-2 Omicron variant infection

  • Xuechuan Li,
  • Hongyi Zhu,
  • Peipei Xu,
  • Jie Zhang,
  • Zhe Wang,
  • Hui He,
  • Fang Shen,
  • Yi Jiang,
  • Lijuan Shen,
  • Jing Xiang,
  • Linhua Yang,
  • Chao Yang,
  • Hao Jiang,
  • Ganglong Gao,
  • Junshuo Jin,
  • Huojian Shen,
  • Yinping Wang,
  • Linshi Wu,
  • Changlin Qian,
  • Dejun Liu,
  • Weiqing Qiu,
  • Qiwei Li,
  • Yuanwen Chen,
  • Fujun Lin,
  • Yun Liu

DOI
https://doi.org/10.3389/fimmu.2024.1486352
Journal volume & issue
Vol. 15

Abstract

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IntroductionThe coronavirus disease 2019 (COVID-19) global pandemic has been the most severe public health emergency since 2019. Currently, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the most dominant. The most prominent symptom of SARS-CoV-2 infection is respiratory. Meanwhile, the fatality of COVID-19 was mainly from pneumonia. However ,in patients with SARS-CoV-2 infection who have pneumonia and those who do not, the differences in the immune repertoire still require further investigation.MethodsWe conducted seven-chain adaptome immune repertoire analyses on patients with SARS-CoV-2 Omicron infection, both with and without pulmonary infiltration.ResultsPatients with pulmonary infiltration exhibit lymphopenia, a decreased proportion of the overall TCR repertoire alongside an increased BCR repertoire, reduced IGHD and IGHM isotype expression, a shorter mean CDR3 length for TRG, and a longer mean length for TRD, as well as diminished clonality and diversity in the TCR/BCR repertoire. Meanwhile, patients with pulmonary infiltration have distinct V-J gene usage and unique CDR3 signature, as well as BCR class switch recombination pattern. Finally, prior vaccination triggered less BCR IGHM/IGHD somatic hypermutation response, preserved the diversity of the entire adaptive immune repertoire, and provided clinical protection against severe or critical conditions following Omicron infection.DiscussionWe report a unique, comprehensive adaptive immune system signature in patients with pulmonary infiltration, which may serve as potential immunological biomarkers and therapeutic targets.

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