Immunosuppression in kidney transplant recipients with COVID-19 infection - where do we stand and where are we heading?

The appropriate immunosuppressive regimen in kidney transplant recipients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2/COVID-19) infection remains unclear. The impact of direct virus injury complicated by dysregulated hyperimmune response with overwhelming release of various cytokines in COVID-19 infected subjects contributes to the complexity of management. The largest concern of the practicing clinicians at current time is how to tailor maintenance immune-modulating therapy during active viral infection and the efficacy of the soon-to-be upcoming immunization for COVID-19. This targeted review aims to cover most of the current evidence on the effect of key maintenance immunosuppressive agents in COVID-19 infection and proposes a line of management to specific scenarios on this very rapidly evolving subject.

Renal allograft surveillance with allospecific T-cytotoxic memory cells.

BACKGROUND: Allo-antigen-specific T-cytotoxic memory cells (TcM) which express CD40 ligand (CD154) in overnight lymphocyte co-culture are strongly associated with acute cellular rejection (ACR) seen in "for cause" biopsies for renal allograft dysfunction. Specifically, when the likelihood of rejection is increased, donor-specific allospecific TcM exceed those induced by HLA-non-identical third-party cell by 1.15-fold or greater. METHODS: The performance of allospecific TcM was evaluated retrospectively in primary renal transplant recipients (RTR) at routine clinical visits, cross-sectionally at presentation for biopsies, and serially. Performance metrics were sensitivity, specificity, positive and negative predictive values (PPV and NPV). RESULTS: Twenty-two primary RTR, median age 45 years (range 19-72) were tested with allospecific CD154 + TcM. Samples were obtained at the mean ± SD time interval of 806 ± 239 days after kidney transplantation. Six of 22 patients experienced biopsy proven T- Cell Mediated Rejection (TCMR). A seventh showed antibody mediated rejection (ABMR). Of these seven patients six demonstrated increased likelihood of rejection with allospecific TcM (sensitivity 83%). Ten of these 15 patients with no rejection had a negative test (specificity 67%). False positive tests were seen in five patients. Six out of 11 patients with positive tests had ACR/ABMR with a PPV of 54%, while 10 out of 11 patients with negative tests were non-rejecters with a NPV of 91%. CONCLUSION: Allospecific T-cytotoxic memory cells distinguished primary RTR with quiescent allografts from those with dysfunction. With serial surveillance measures, this test system may facilitate decisions to manage immunosuppression in RTR.

ABO incompatibility in renal transplantation.

ABO blood group incompatibility (ABO-I) was historically considered an absolute contraindication to kidney transplantation due to the significant risk of acute antibody-mediated rejection and early graft loss. Nevertheless, the urge to minimize the gap between the candidates' number on the waitlist for kidney transplants and the available kidney donors encourage investigation into finding ways to use organs from ABO-I kidney donors, especially in the era of using more potent immunosuppression therapies. This review aims to discuss a general overview of ABO-I kidney transplantation and the different protocols adopted by some transplant centers to meaningfully overcome this barrier.

Qualitative Assessment of Early Adverse Effects of Pfizer-BioNTech and Sinopharm COVID-19 Vaccines by Telephone Interviews.

Vaccines are considered the best approach for countering the COVID-19 pandemic. In this study, we compared early side effects associated with vaccination with the Sinopharm and Pfizer-BioNTech COVID-19 vaccines. Participants of this observational cohort were interviewed based on semi-structured telephone interviews, with enquiries about side effects that developed after vaccination with each dose of these vaccines. Overall, 1004 participants were enrolled, of which 51.1% received Sinopharm vaccine and 48.9% received the Pfizer-BioNTech vaccine. After the first dose, 46.3% of participants had an adverse reaction, with injection site pain most commonly being reported (33.2%). Participants who received the Pfizer-BioNTech vaccine had significantly higher frequencies of all types of adverse reactions (p < 0.01), with no significant differences in the duration of adverse reactions between the two vaccines. Regarding the second dose, 48.6% of participants had adverse reactions, with injection site pain being most commonly reported (29%). Those who received the Pfizer vaccine reported higher frequencies of all adverse reactions (p < 0.01). However, a longer duration of adverse reactions was seen among Sinopharm vaccine recipients as compared to Pfizer-BioNTech vaccine recipients (p = 0.01). In conclusion, early adverse effects are reported following all types of vaccines but these are more likely to be encountered following the administration of new-generation vaccines. These side effects are mostly mild and treatable.