Responder Profiles

"Our analysis revealed distinct immunological architectures that differentiate fast responders from slow responders to SARS-CoV-2 infection. In fast responders, the immune landscape is dominated by cytolytic cells, including NK cells and NKG2D⁺CD8⁺ T cells, as well as pDCs. In contrast, slow responders exhibited a Tfh-dominated profile. This divergence likely reflects differences in the timing and pathways of immune activation. Tfh cells are critical for orchestrating germinal center formation and facilitating antibody affinity maturation—processes that require sustained antigen exposure and cellular coordination. Slow responders showed increased Tfh activity alongside higher-affinity antibodies, consistent with a delayed but robust engagement of the adaptive humoral response. Tfh cells were also involved in ADCC, which depends on class-switched, high-affinity antibodies and thus requires time to develop. Conversely, the immune features of fast responders point toward a more rapid process involving both cytolytic effector functions and noncanonical B cell activation. pDCs have been shown to enhance T cell-independent B cell responses through a p38 MAPK–STAT1 signaling pathway, enabling early antibody production without the need for CD4⁺ T cell help. Similarly, NKG2D signaling in CD8⁺ T cells has been implicated in supporting memory responses in the absence of CD4⁺ T cell assistance. These mechanisms may collectively support the early control of viral replication observed in fast responders. In the CyTOF-based assay, CD107a/b was used to reflect NK degranulation events that can arise from antibody-mediated activation. The CD107a/b⁺ population accounted for approximately 10.8 ± 4.2% in the 5SB12 group, which is within the range reported in ADCC assays using similar experimental settings. These findings suggest that only specific NK subpopulations are activated and participate in SARS-CoV-2 antibody-involved ADCC."