Prolonged persistence of tissue‐resident memory cells in the upper airway following SARS‐CoV‐2 infection and vaccination

Abstract Objectives Here, we characterised the diversity and persistence of immunological memory cells—particularly tissue‐resident memory T (TRM) and B (BRM) cells—in the nasopharyngeal lymphoid tissues of healthy vaccinated (HV) individuals and those who experienced SARS‐CoV‐2 breakthrough infection (BR). Methods Nasopharynx (NP) samples were obtained using brushing from HV and BR subjects. Immune cell populations were analysed using transcriptomic profiling and flow cytometry. Results Transcriptomic profiling revealed that the NP of SARS‐CoV‐2‐infected individuals exhibited distinctive signatures of lymphocyte‐mediated immunity, underscoring its role as a key site for viral invasion and immune activation. Effector memory CD4+ and CD8+ T (TEM) cells, along with non‐germinal center (GC) B cells, predominated in the NP. Although overall frequencies of memory T cells were comparable between HV and BR groups, CD4+ TEM and GC B cells were significantly enriched in the NP of BR individuals at least 1 year post infection. Notably, over 80% of CD4+ TEM and 40% of CD8+ TEM cells were TRM, and more than 30% of memory B cells exhibited a BRM phenotype. These populations of CD4+, CD8+ TRM and BRM persisted in the NP for over 2 years following SARS‐CoV‐2 infection or vaccination. In particular, CD4+ TRM cells were significantly more abundant and durably maintained in the NP mucosa of BR individuals. Conclusion Our findings identify the nasopharynx as a key site of long‐lived immunological memory, marked by persistent TRM and BRM cells after SARS‐CoV‐2 exposure.