Background: Lymohopenia, in particular depressed levels of CD4⁺T and B cells is an important consideration when assessing the effectiveness of vaccine responses. Blood donors, in particular frequent platelet donors (>20 donations annually) have been shown recently to exhibit severe plateletpheresis-associated lymphopenia; in particular CD4⁺T but not B cell numbers are decreased. COVID-19 vaccination thereby provides a model to assess whether lymphopenic platelet donors present compromised humoral immune responses.

Methodology:43 plateletpheresis donors with a range of pre-vaccination CD4⁺T cell counts (76-1537 cells/µl) who had received 2 doses of COVID-19 vaccination were recruited for the study. At least half of these individuals were frequent platelet donors and thus were likely to display lowCD4⁺T cell counts. In addition to baseline T cell measurements by flow cytometry, antibody binding assays to full-length Spike and the Receptor Binding Domain (RBD) were performed pre- and post-vaccination. Furthermore, pseudo-particle neutralization and antibody-dependent cellular cytotoxicity (ADCC) assays were conducted to measure antibody functionality.

Results: Participants were stratified into two groups: <400 CD4/µl (n=27) and ≥400 CD4/µl (n=16). Following the first dose, 79% seroconverted within the <400 CD4/µl group compared to 87% in the ≥400 CD4/µl group; all donors were seropositive post-second dose with significant increases in antibody levels. Importantly differences in CD4⁺ T cell levels minimally impacted neutralization, Spike recognition and IgG Fc-mediated effector functions.

Discussion: Overall, our results suggest that lymphopenic plateletpheresis donors do not exhibit significant immune dysfunction; they have retained the T and B cell functionality necessary for potent antibody responses after vaccination.