The
COVID-19 pandemic posed a major threat to immunocompromised patients,
particularly kidney transplant recipients (KTRs), who are at increased risk of
severe disease and mortality. Despite the effectiveness of mRNA-based
vaccination in the general population, KTRs showed impaired immune responses,
partly related to immunosuppressive therapy.
Part I –
Preventive measures
KTRs showed high adherence to preventive measures before vaccination, which
decreased after vaccination. Those informed of an antibody response adhered
less to preventive measures. Higher adherence was associated with lower
SARS-CoV-2 infection rates, demonstrating the effectiveness of preventive
measures and highlighting the behavioral consequences of sharing antibody
results.
Part II
– Vaccination strategies and nonseroconversion
Repeated mRNA-1273 vaccination was the most effective strategy for KTRs who
failed to seroconvert, whereas double-dose vaccination, heterologous
vaccination, and temporary MMF/MPA discontinuation did not further improve
antibody responses. Two-week MMF/MPA interruption did not cause acute
rejection. A prediction model identified MMF/MPA use as the strongest predictor
of nonseroconversion, with a dose-dependent negative association with antibody
formation.
Part III
– B cell responses and IgG4
S-specific B cells persisted for at least six months after vaccination,
although approximately half of KTRs lacked detectable responses. Repeated vaaccination
was associated with a shift toward IgG4. This IgG4 skewing was associated with
reduced Fc-mediated antibody functions, while neutralizing capacity remained
preserved.
Together,
these findings provide insight into the societal, clinical, and translational
impact of COVID-19 in KTRs, from bedside to bench.
The studies
in this thesis were conducted within the Dutch REnal patients COVID-19
VACcination (RECOVAC) consortium.
