design and the heterogeneity of the patient pop­ulations, and thus their findings are difficult to interpret [79–84].

became evident that the COVID-19 vaccina­tion immune paresis of SOTRs translated into a clinical picture that included an unaccept­ably increased risk of breakthrough infections and mortality in vaccinated transplant recipi­ents [5, 45, 46]. The increased risk of break­through infections varied with the underlying immunocompromising diagnosis and occurred substantially faster in individuals with immune dysfunction than in the general population [4,

vaccination may not necessarily lead to com­plete susceptibility to severe disease because SARS-CoV-2 specific T-cell responses are an important factor in the development of protec­tive immunity against viral infection [126]. Vaccine-induced spike-specific T cells are mul­tispecific and can recognize different regions of the spike protein [127, 128]. Thus, despite the ability of emerging variants to alter T-cell speci­ficity, these variants do not escape the entire repertoire of spike-specific T cells. Indeed, it has been demonstrated that, for most vaccinated individuals, VOCs are recognized by the spike­specific T cells induced by mRNA vaccines [129, 130].

infection that are different from—and can be used in conjunction with—the sole strategy of repeated booster doses to protect this high-risk population. In the context of repeated COVID­19 vaccination in patients treated with immu­nosuppressive drugs, increasing the dose of the mRNA-1273 vaccine had no beneficial effect [133]. Data indicates that lengthening the time interval between mRNA COVID-19 vaccine doses may improve the immune response and vaccine effectiveness. A tendency toward higher neutralization inhibition was seen for a longer interval between the first and second BNT doses in SOTRs [134]. Therefore, follow-up studies must be conducted to determine the optimal vac­cination interval for better vaccine efficacy in immunocompromised SOTRs, who are expected to have reduced vaccine-induced immunogenic­ity. Patients on the transplant waiting list show a slightly reduced response to vaccination, com­pared to the healthy population, but a signifi­cantly better response than transplant recipients [135, 136]. HTx recipients vaccinated with two doses of the BNT162b2 vaccine prior to trans­plant demonstrated a high and durable immune response at 12 weeks after HTx [137]. Similarly, the anti-SARS-CoV2 antibody titers in kidney recipients vaccinated prior to transplant were persistently higher than those in recipients vac­cinated after transplant. Thus, it is recommended that all transplant candidates receive a full SARS-Cov-2 vaccine cycle before transplant. The net benefit of reducing or withdrawing immunosuppressive drugs aiming to improve the response to SARS-CoV2 vaccination is still under investigation, and currently, the strategy cannot be recommended or excluded in this context. Passive immunization with preformed single-conformation monoclonal antibodies can potentially support an immune defense against SARS-CoV2 in SOTRs. However, due to the specificity of the immune support provided by monoclonal antibodies, caution must be exer­cised in applying such a strategy in light of the evolution of novel VOCs characterized by high degree of genomic mutations associated with evasion. Findings to date support updat­ing COVID-19 vaccines to match antigenically