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

Summary

Using single-cell RNA sequencing of nasopharyngeal swabs from vaccinated and unvaccinated adults across ancestral, Delta, and Omicron waves, the study shows that Delta and Omicron infections share similar nasal cellular compositions, with myeloid and T cell populations and viral transcripts driving patterns. The integrated dataset illuminates how variants and vaccination status shape mucosal immune landscapes.

Key Findings

• Single-cell RNA-seq of nasopharyngeal swabs across ancestral, Delta, and Omicron infections revealed that Delta and Omicron share similar nasal cellular compositions.
• Myeloid and T cell populations, together with SARS-CoV-2 transcripts, prominently shaped the observed nasal immune landscape.
• Integrated analysis spanning vaccinated and unvaccinated adults contextualized how vaccination status and variant identity influence mucosal responses.

Clinical Implications

Insights into variant- and vaccine-modulated nasal immunity can inform mucosal vaccine strategies, timing of boosters, and therapeutic targeting of innate/adaptive responses in the upper airway.

Limitations

• Cross-sectional sampling during acute infection limits causal inference over time
• Sample size and batch effects are not detailed in the abstract

Future Directions

Longitudinal single-cell profiling across infection timelines and booster doses, linking mucosal immunity to transmission, symptomatology, and vaccine effectiveness.