Fig. 7: Graphical summary of the main findings in this study.

The focus of the study was to identify T cell responses against SARS-CoV-2 in paired blood and lung tissue samples of patients that recovered from COVID-19 between 4 to 12 months ago (convalescent infection, left panel) and patients that were uninfected and mRNA vaccinated either between 4 to 10 months ago (LT long term, right panel) or between 1 and 2 months ago (ST short term, right panel). Left: Infection with SARS-CoV-2 triggers the immune system to respond against multiple viral proteins, including the M, N, and S proteins. In the blood of convalescent patients, CD4⁺ T cells responded to M, N, and S peptides by producing IFNγ and both CD4⁺ and CD8⁺ T cells responding to M and N peptides by producing IFNγ and CD107a. Moreover, in the lung of these patients, we found T cells with mainly T_RM (CD69⁺CD103⁺ and CD69⁺CD103^-) phenotypes producing IFNγ or a combination of IFNγ and CD107a. Right: mRNA-vaccinated patients are only exposed to mRNA encoding for the SARS-CoV-2 S protein. In the blood of LT vaccinated patients, CD8⁺ T cells responded to S peptides by producing CD107a and CD4⁺ and CD8⁺ producing IFNγ and CD107a. In the blood of ST-vaccinated patients, the response to S peptides mainly consisted of CD4⁺ T cells producing IFNγ and CD4⁺ and CD8⁺ producing IFNγ and CD107a. In contrast to T cell responses in the lung of convalescent-infected patients, both LT and ST mRNA-vaccinated patients showed a less prominent IFNγ response mainly produced by CD69⁺CD103^- T_RM cells and non-T_RM cells. Last, CD69⁺CD103⁺ T_RM producing IFNγ and CD107a were virtually absent in the lungs of these vaccinated patients.