Single-cell immune profiling of matched disease and recovery phase blood of COVID-19 patients reveals anti-LAG3 based immune checkpoint therapy as a promising option

We profiled the circulating immune cells in COVID-19 patients during the active disease and recovery phases via single cell RNA, TCR and BCR sequencing in order to elucidate the key anti-virus adaptive immune responses, and explore potential immunomodulatory therapeutic strategies. T cell competence plays a dominant role in anti-SARS-CoV-2 immunity. Clonally expanded CD4 T effector cells averted CD8 T cell exhaustion, and expansion of multiple CD8 T effector/memory clones was correlated with rapid virus clearance. In contrast, the patients lacking CD4 TEFF cell clonal expansion harbored exhausted CD8 TEFF cells co-expressing multiple co-inhibitory molecules. In addition, more than 90% of the exhausted cells expressed at least 2 and more than half of exhausted cells expressed at least 4 inhibitory molecules. Furthermore, co-expression of LAG3, Galectin-9, and SLAMF6 is the inhibitory molecule expression signature of exhausted T cell population in SARS-CoV-2 infection. Our findings indicate that LAG3-based immune checkpoint blockade is a promising strategy for treating COVID-19.