A recent study published in Nature Immunology, co-authored by Ragon Institute faculty member Alex K. Shalek, PhD, provides critical insights into how SARS-CoV-2 variants and vaccination status shape immune responses in the nasal mucosa. This research, which utilized advanced single-cell RNA sequencing (scRNA-seq) approaches, explores how cellular responses in the human nasal cavity differ across viral variants and vaccination statuses, offering new perspectives on COVID-19 immunity.
The study examined nasopharyngeal swabs from vaccinated and unvaccinated adults infected with Delta, Omicron, or ancestral strains of SARS-CoV-2. By integrating datasets, the researchers identified key distinctions in nasal cell composition and immune activation, advancing our understanding of how the immune system responds to evolving viral threats.
One of the study’s key findings is that Delta and Omicron infections resulted in similar nasal cell compositions, characterized by unique patterns of myeloid, T cell, and SARS-CoV-2-enriched epithelial cell subsets. This was in contrast to ancestral infections, which showed markedly different immune profiles. Delta infections demonstrated a significant increase in viral RNA and an enrichment of PER2+EGR1+GDF15+ epithelial cells, which were consistently associated with SARS-CoV-2 RNA across variants.
Vaccination also played a critical role in modulating immune responses. Vaccinated individuals exhibited an increased frequency and activation of nasal macrophages, highlighting the protective impact of vaccination on the mucosal immune system. Additionally, the study found that the expression of interferon-stimulated genes correlated negatively with disease severity in patients infected with ancestral and Delta variants but not with Omicron, underscoring key differences in immune dynamics across variants.
The study represents a significant step forward in understanding the complexities of SARS-CoV-2 immunity, particularly in the context of variant evolution and vaccination. These findings will potentially help inform the development of future treatment strategies, enhancing global preparedness for ongoing and future pandemics.