Characterization of type 2 diabetes-related immune response heterogeneity to COVID-19 vaccines via single-cell landscape analyses

Vaccines provide the most ideal protection against COVID-19, but variants of concern are highly transmissible and less sensitive to vaccine-elicited antibodies. It is unknown whether patients with type 2 diabetes (T2D) can develop vaccine-elicited immune responses equal to those in healthy individuals. Impaired neutralizing antibodies and spike specific antibodies against SARS-CoV-2 have been identified in T2D patients vaccinated with inactivated vaccine. We therefore investigated changes in the peripheral immune systems of vaccinated T2D patients using single-cell RNA-sequencing. The immune cell phenotypes comprised antigen-presenting (APC), T, and plasma cell reconfigurations. Humoral immune damage to plasma cells exhibited impaired protein synthesis, processing, and transport. APCs were characterized by inflammation following human leukocyte antigen downregulation, neutrophil recruitment, and type I interferon pathway defects. Oxidative stress yielded abnormal hyper-inflammation comprising hyper-cytotoxic CD4 + and CD8 + T cells. There was also a decreased subset of SARS-CoV-2-specific B and T cell receptors. These results provide mechanistic insights into the COVID-19 vaccine-elicited immune responses of T2D patients.