Robust mucosal SARS-CoV-2-specific T cells effectively combat COVID-19 and establish polyfunctional resident memory in patient lungs.

Summary

In 159 COVID-19 patients, single-cell profiling revealed robust, polyfunctional SARS-CoV-2–specific T cells in BALF that correlate with lower viral loads and better respiratory metrics, distinct from blood T cells. These cells persist as tissue-resident memory after clearance, underscoring mucosal T cell roles in protection and recovery.

Key Findings

• SARS-CoV-2–specific T cells are robustly induced in BALF regardless of prior vaccination.
• BALF T cell polyfunctionality and glycolysis signatures correlate with lower viral loads and better respiratory function.
• After viral clearance, BALF SARS-CoV-2–specific T cells persist as polyfunctional tissue-resident memory.

Clinical Implications

Supports strategies to elicit mucosal T cell immunity (e.g., intranasal vaccines) and suggests BALF T cell profiling could aid prognosis and recovery assessments.

Limitations

• Observational design limits causal inference on protection mechanisms
• BALF sampling may select for hospitalized or procedurally eligible patients

Future Directions

Test whether intranasal or mucosal vaccines enhance similar BALF T cell profiles and validate minimally invasive surrogates for mucosal immunity.