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

Walsh, J. M. L, Miao, V. N, Owings, A. H, Tang, Y, Bromley, J. D, Kazer, S. W, Kimler, K, Asare, C, Ziegler, C. G. K, Ibrahim, S, Jivanjee, T, George, M, Navia, A. W, Drake, R, Parker, A, Billingsley, B. C, Dotherow, P, Tarugu, S, Kota, S. K, Laird, H, Wichman, T. G, David, Y. T, Dhaliwal, N. S, Pride, Y, Guo, Y, Senitko, M,, Harvey, J, Bates, J, Diamond, G, Garrett, M. R, Robinson, D. A, Frame, I. J, Lyons, J. J, Robinson, T. O, Shalek, A. K, Horwitz, B. H, Glover, S. C, Ordovas-Montanes, J.

Nature Immunology, 26, 294, February, 2025

Abstract

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.

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