Abstract and Introduction
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination may fail to sufficiently protect transplant recipients against coronavirus disease 2019 (COVID-19). We retrospectively evaluated COVID-19 in kidney transplant recipients (n = 226) after BNT162b2 mRNA vaccine administration. The control group consisted of unvaccinated patients (n = 194) during the previous pandemic wave. We measured anti-spike protein immunoglobulin G (IgG) levels and cellular responses, using enzyme-linked immunosorbent spot assay, in a prospective cohort after vaccination (n = 31) and recovery from COVID-19 (n = 19). COVID-19 was diagnosed in 37 (16%) vaccinated and 43 (22%) unvaccinated patients. COVID-19 severity was similar in both groups, with patients exhibiting a comparable need for hospitalization (41% vs. 40%, p = 1.000) and mortality (14% vs. 9%, p = .726). Short posttransplant periods were associated with COVID-19 after vaccination (p < .001). Only 5 (16%) patients achieved positive SARS-CoV-2 IgG after vaccination, and 17 (89%, p < .001) recovered from COVID-19 (median IgG levels, 0.6 vs. 52.5 AU/ml, p < .001). A cellular response following vaccination was present in the majority (n = 22, 71%), with an increase in interleukin 2 secreting T cells (p < .001). Despite detectable T cell immunity after mRNA vaccination, kidney transplant recipients remained at a high risk of severe COVID-19. Humoral responses induced by vaccination were significantly lower than that after COVID-19.
Introduction
Kidney transplant patients are among the most vulnerable to severe coronavirus disease 2019 (COVID-19) that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high percentage of kidney recipients require hospitalization, and most studies indicate that mortality among them ranges between 10 and 30%.[1–6] In addition to chronic immunosuppression, adverse outcomes can be accounted for by the high proportion of kidney recipients who are elderly or have associated comorbidities.[3–6] Given the limited therapeutic options available, maximal efforts are directed toward the prevention of COVID-19.
Vaccination against SARS-CoV-2 is the preferred route to mitigate the impact of COVID-19. New mRNA vaccines show robust humoral and T cell immune responses and provide 95% protection against COVID-19 in the non-transplant population, including in elderly patients and those with comorbidities.[7–9] The vaccine is highly efficacious even against SARS-CoV-2 variants of concern, such as B.1.1.7 (alpha) or B.1.617.2 (delta).[10,11] Despite the fact that solid organ transplant recipients have not been included in COVID-19 vaccine trials, vaccination is recommended in this population.[12] Kidney transplant recipients may exhibit long-term viral shedding; however, a significant majority develop anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies and polyfunctional T cell immunity in levels that are comparable to non-immunosuppressed patients.[13–17] Despite these promising data, a number of authors have reported poor humoral responses in transplant recipients after mRNA vaccination.[18–22] Nevertheless, in contrast to the humoral response, cellular immunity was detected in a significantly high proportion of patients.[22,23] From a clinical point of view, protection against COVID-19 in vaccinated patients after kidney transplantation remains unclear.
To determine the efficacy of vaccination, we retrospectively evaluated a cohort of kidney transplant recipients who received the BNT162b2 mRNA vaccine during January 2021, when the COVID-19 pandemic was at its peak in the Western Bohemia region. When the study began, the region experienced a 7-day incidence of 528 new cases per 100 000 population. The pandemic then peaked in March 2021, with values of 1050 new cases per 100 000 population (the "winter wave"), which corresponded to the highest incidence to date since the beginning of the pandemic. The course of COVID-19 was compared among a group of unvaccinated renal transplant recipients during the "autumn wave" of the pandemic, which began in early September 2020 with a 7-day incidence of 78 new cases per 100 000 population and peaked in late October 2020 at 817 cases per 100 000 population. In a follow-up prospective study, we measured the humoral and cellular immune responses after vaccination in another cohort who was vaccinated in February 2021 and compared them to the responses in patients who had recovered from COVID-19.
American Journal of Transplantation. 2022;22(3):801-812. © 2022 Blackwell Publishing
