ABSTRACT
Introduction: Studies have shown reduced antiviral responses in kidney transplant recipients (KTRs) following SARS-CoV-2 mRNA vaccination, but data on post-vaccination alloimmune responses and antiviral responses against the Delta (B.1.617.2) variant are limited. Materials and methods: To address this issue, we conducted a prospective, multi-center study of 58 adult KTRs receiving mRNA-BNT162b2 or mRNA-1273 vaccines. We used multiple complementary non-invasive biomarkers for rejection monitoring including serum creatinine, proteinuria, donor-derived cell-free DNA, peripheral blood gene expression profile (PBGEP), urinary CXCL9 mRNA and de novo donor-specific antibodies (DSA). Secondary outcomes included development of anti-viral immune responses against the wild-type and Delta variant of SARS-CoV-2. Results: At a median of 85 days, no KTRs developed de novo DSAs and only one patient developed acute rejection following recent conversion to belatacept, which was associated with increased creatinine and urinary CXCL9 levels. During follow-up, there were no significant changes in proteinuria, donor-derived cell-free DNA levels or PBGEP. 36% of KTRs in our cohort developed anti-wild-type spike antibodies, 75% and 55% of whom had neutralizing responses against wild-type and Delta variants respectively. A cellular response against wild-type S1, measured by interferon-γ-ELISpot assay, developed in 38% of KTRs. Cellular responses did not differ in KTRs with or without antibody responses. Conclusions: SARS-CoV-2 mRNA vaccination in KTRs did not elicit a significant alloimmune response. About half of KTRs who develop anti-wild-type spike antibodies after two mRNA vaccine doses have neutralizing responses against the Delta variant. There was no association between anti-viral humoral and cellular responses.
Subject(s)
2019-nCoV Vaccine mRNA-1273/immunology , BNT162 Vaccine/immunology , Graft Rejection/diagnosis , Kidney Transplantation , Monitoring, Physiologic/methods , SARS-CoV-2/immunology , Aged , Antibodies, Viral/blood , Enzyme-Linked Immunospot Assay , Female , Humans , Immunity, Cellular , Isoantibodies/blood , Male , Middle Aged , Prospective Studies , Transplantation, Homologous , VaccinationABSTRACT
CONTEXT: Chronic immunosuppression is associated with an increased risk of opportunistic infections. Although kidney transplant recipients with coronavirus disease 2019 (COVID-19) have higher mortality than the general population, data on their risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are unknown. Subject of Review: A recent single-center screening study from the UK (Transplantation. 2021 Jan 1;105(1):151-7) showed that 89 (10.4%) of 855 consecutive kidney transplant recipients tested positive for SARS-CoV-2 antibodies. Risk factors for infection included a nonwhite background, diabetes, and a history of allograft rejection. Risk factors for mortality in individuals who developed COVID-19 were older age and receiving steroids. Second Opinion: This study shows that the rate of SARS-CoV-2 infection in kidney transplant recipients is similar to the one observed in the general population in the same area (13%), indicating that transplant recipients are not at increased risk of COVID-19. However, the investigators raise the interesting point that since transplant individuals were advised to shelter earlier than the general population, they may be in fact more susceptible. This statement is hard to substantiate, but the identification of specific risk factors for infection and poor outcomes is crucial to tailor strategies to prevent spread of the infection. This is particularly important, considering that kidney transplant recipients may be at increased risk of prolonged viral spread and in-host viral mutations, making them not just a particularly fragile population for COVID-19 but also a potentially major source of further contagions.