Unraveling the immune landscape and molecular signatures of antibody-dependent cellular cytotoxicity in SARS-CoV-2 clearance - CyTOF fcs files

Beyond direct neutralization, antibodies clear SARS-CoV-2 by triggering antibody-dependent cellular cytotoxicity (ADCC), which guides natural killer (NK) cells to eliminate infected cells. To understand ADCC's role in COVID-19, we analyzed samples from initial patients and found that plasma ADCC activity was linked to a slower rate of viral clearance. To explore this mechanism, we isolated a monoclonal antibody with potent ADCC activity against SARS-CoV-2 variants. This antibody activated an antiviral transcriptional program in the lungs of infected mice that suppressed viral RNA transcription. Spatial transcriptomic analysis in ADCC antibody-treated mice revealed the high expression of weakly cytolytic NK cell markers and NK cell cluster-associated gene pathways related to viral clearance in the lungs. Furthermore, human peripheral NK cells engaging the ADCC antibody activated the pre-existing NK cell clusters. Our findings underscore the coordinated action between ADCC-inducing antibodies and specific NK cell subsets with low cytotoxic activity during SARS-CoV-2 infection.