Concerning durability, this project will keep ongoing and evaluate cellular and humoral immunity at 6 and 12 months. only 63.3% of KT patients seroconverted with a very low antibody level. A positive IGRA was documented in 96.9% of controls, 89.3% peritoneal dialysis, 77.6% hemodialysis, 61.3% of KT patients transplanted more than 1 year ago and only 36% of those transplanted within the previous 12 months. Overall, 100% of healthy controls, 95.4% of dialysis patients and 78.8% KT recipients developed any immune response (humoral and/or cellular) against SARS-CoV-2. KT patients showed low rates of immune responses to mRNA Coronavirus infectious disease 2019 vaccines, especially those with recent transplantations. Simple humoral and cellular monitoring is advisable, so that repeated doses may be scheduled according to the results. KEYWORDS: antibody biology, clinical research/practice, dialysis, immunobiology, COVID-19, infectious disease, kidney transplantation/nephrology, T cell biology, vaccine Abbreviations: AE, adverse events; AUC, area under the curve; CI, confidence interval; CKD, chronic kidney disease; COVID-19, coronavirus infectious disease 2019; eGFR, estimated glomerular filtration rate; HD, hemodialysis; IFN, interferon gamma; IGRA, interferon gamma release assay; IQR, interquartile range; KT, kidney transplant; PD, peritoneal dialysis; ROC, receiver operating characteristic; PF-543 S, Spike protein; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; Th1, T helper 1 1.?INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus infectious disease 2019 (COVID-19), which has caused the PF-543 worst pandemic in the last decades. COVID-19 cases can be asymptomatic or mild in around 80% of individuals, especially in young adults and children. However, patients over 60 years old and with comorbidities are in major risk, requiring intensive respiratory support and presenting more frequently complications such as multiorganic failure or death.1 , 2 Several studies indicate that chronic kidney disease (CKD) is the Mouse monoclonal to SKP2 most common comorbidity in severe COVID-19.3, 4, 5, 6 Furthermore, patients on renal replacement therapy, on dialysis or with a kidney transplant (KT), have shown the highest morbidity and mortality.3 , 7, 8, 9 A functional immune system is essential to overcome SARS-CoV-2 infection. In the acute phase, activation of CD4 and CD8-T cells is observed in most infected patients. CD4-T cells conduct T helper 1 (Th1) responses, expressing cytokines like interferon gamma (IFN) that contribute to viral clearance. CD8-T cells directly destroy infected cells through cytotoxicity.10 , 11 Regarding humoral response, SARS-CoV-2 antigen-specific antibodies are detected in the first weeks since symptoms onset, reaching peak levels in the third week. Neutralizing antibodies, which bind to the Spike (S) protein and prevent interaction with the cellular receptor ACE2 are also generated, granting immune protection against SARS-CoV-2 by disabling viral entry.11 Antibody durability has not yet been uniformly established, although some studies suggest that levels decrease just after reaching a peak.12 , 13 Despite this, as antibody levels that offer protection have not been determined, this decrease may not imply loss of immunity against reinfections.10 Two studies have shown persistence of antibody and cellular responses 6 months after COVID-19 in over 100 adult hemodialysis (HD) patients.14 , 15 Transplant recipients can also show robust although delayed humoral and cellular responses after infection.16 , 17 Since the beginning of the pandemic, governments of states affected by COVID-19 implemented sanitary measures to limit virus propagation and reduce high morbidity and mortality rates. The most suitable way to achieve these objectives is generating herd immunity with vaccines.18 Vaccines must induce antibody production and T cell activation to prevent infection and spread to others.19 Cellular immunity stimulated by mRNA-1273 is characterized by activation of S-specific CD4-T cells with Th1 profile, while BNT162b2 additionally induces a considerable CD8-T cell response,20 , 21 and both induce antibodies against the S protein. Due to the increased risk of severe and fatal COVID-19 in KT patients, they have been prioritized for COVID-19 vaccination. Because the response to several vaccines is recognized to be poorer in these patients,22 , 23 it is imperative to assess the proportion of responders, the quality of the response as well as the best time for vaccination across the lifetime of the CKD patient with simple and reliable immune response tools. In 104 heart and liver transplant recipients, 64% developed antibodies and 79% T cell responses measured with ELISPOT against the S protein 1 month after completing mRNA-1273 vaccination.24 Although ELISPOT responses have been documented in transplant recipients,24, 25, 26 the technique is time-consuming and cumbersome. Thus, we designed a cohort study PF-543 to assess and compare antibody.