<p>Viral variant and host vaccination status impact infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet how these factors shift cellular responses in the human nasal mucosa remains uncharacterized. We performed single-cell RNA sequencing (scRNA-seq) on nasopharyngeal swabs from vaccinated and unvaccinated adults with acute Delta and Omicron SARS-CoV-2 infections and integrated with data from acute infections with ancestral SARS-CoV-2. Patients with Delta and Omicron exhibited greater similarity in nasal cell composition driven by myeloid, T cell and SARS-CoV-2<sup>hi</sup> cell subsets, which was distinct from that of ancestral cases. Delta-infected samples had a marked increase in viral RNA, and a subset of <i>PER2</i><sup>+</sup><i>EGR1</i><sup>+</sup><i>GDF15</i><sup>+</sup> epithelial cells was enriched in SARS-CoV-2 RNA<sup>+</sup> cells in all variants. Prior vaccination was associated with increased frequency and activation of nasal macrophages. Expression of interferon-stimulated genes negatively correlated with coronavirus disease 2019 (COVID-19) severity in patients with ancestral and Delta but not Omicron variants. Our study defines nasal cell responses and signatures of disease severity across SARS-CoV-2 variants and vaccination.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Variants and vaccines impact nasal immunity over three waves of SARS-CoV-2

  • Jaclyn M. L. Walsh,
  • Vincent N. Miao,
  • Anna H. Owings,
  • Ying Tang,
  • Joshua D. Bromley,
  • Samuel W. Kazer,
  • Kyle Kimler,
  • Chelsea Asare,
  • Carly G. K. Ziegler,
  • Samira Ibrahim,
  • Tasneem Jivanjee,
  • Micayla George,
  • Andrew W. Navia,
  • Riley S. Drake,
  • Adam Parker,
  • Benjamin C. Billingsley,
  • Paul Dotherow,
  • Spurthi Tarugu,
  • Sai K. Kota,
  • Hannah Laird,
  • T. Grant Wichman,
  • Yesenia T. Davis,
  • Neha S. Dhaliwal,
  • Yilianys Pride,
  • Yanglin Guo,
  • Michal Senitko,
  • Jessie Harvey,
  • John T. Bates,
  • Gill Diamond,
  • Michael R. Garrett,
  • D. Ashley Robinson,
  • I. J. Frame,
  • Jonathan J. Lyons,
  • Tanya O. Robinson,
  • Alex K. Shalek,
  • Bruce H. Horwitz,
  • Sarah C. Glover,
  • Jose Ordovas-Montanes

摘要

Viral variant and host vaccination status impact infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet how these factors shift cellular responses in the human nasal mucosa remains uncharacterized. We performed single-cell RNA sequencing (scRNA-seq) on nasopharyngeal swabs from vaccinated and unvaccinated adults with acute Delta and Omicron SARS-CoV-2 infections and integrated with data from acute infections with ancestral SARS-CoV-2. Patients with Delta and Omicron exhibited greater similarity in nasal cell composition driven by myeloid, T cell and SARS-CoV-2hi cell subsets, which was distinct from that of ancestral cases. Delta-infected samples had a marked increase in viral RNA, and a subset of PER2+EGR1+GDF15+ epithelial cells was enriched in SARS-CoV-2 RNA+ cells in all variants. Prior vaccination was associated with increased frequency and activation of nasal macrophages. Expression of interferon-stimulated genes negatively correlated with coronavirus disease 2019 (COVID-19) severity in patients with ancestral and Delta but not Omicron variants. Our study defines nasal cell responses and signatures of disease severity across SARS-CoV-2 variants and vaccination.