The burden of post COVID-19 condition (PCC) is not well studied in patients with advanced kidney disease. A large prospective cohort of SARS-CoV-2 vaccinated patients with chronic kidney disease stages G4-G5 (CKD G4/5), on dialysis, and kidney transplant recipients (KTR) were included. Antibody levels were determined after vaccination. Presence of long-lasting symptoms was assessed in patients with and without prior COVID-19 and compared using logistic regression. In patients with prior COVID-19, PCC was defined according to the WHO definition. 216 CKD G4/5 patients, 375 dialysis patients, and 2005 KTR were included. Long-lasting symptoms were reported in 204/853 (24%) patients with prior COVID-19 and in 297/1743 (17%) patients without prior COVID-19 (aOR: 1.45 (1.17-1.78)], p<0.001). PCC was prevalent in 29% of CKD G4/5 patients, 21% of dialysis patients, and 24% of KTR. In addition, 69% of patients with PCC reported (very) high symptom burden. Odds of PCC was lower per ten-fold increase in antibody level after vaccination (aOR 0.82 [0.70-0.96], p=0.01) and higher in case of COVID-19 related hospital admission (aOR 4.64 [2.61-8.25], p=0.003). CKD G4/5 patients, dialysis patients, and KTR are at risk for PCC with high symptom burden after SARS-CoV-2 vaccination, especially if antibody levels are low and in case of hospitalization due to COVID-19.

Solid organ transplant recipients (SOTRs) are at high risk of human herpesvirus (HHV)-related morbidity and mortality due to the use of immunosuppressive therapy. We aim to increase awareness and understanding of HHV disease burden in SOTRs by providing an overview of current prevention and management strategies as described in the literature and guidelines. We discuss challenges in both prevention and treatment as well as future perspectives.

T-cell–mediated help to B cells is required for the development of humoral responses, in which the cytokine interleukin (IL)-21 is key. Here, we studied the mRNA-1273 vaccine–induced SARS-CoV-2–specific memory T-cell IL-21 response, memory B cell response, and immunoglobulin (Ig)G antibody levels in peripheral blood at 28 days after the second vaccination by ELISpot and the fluorescent bead–based multiplex immunoassay, respectively. We included 40 patients with chronic kidney disease (CKD), 34 patients on dialysis, 63 kidney transplant recipients (KTR), and 47 controls. We found that KTR, but not patients with CKD and those receiving dialysis, showed a significantly lower number of SARS-CoV-2–specific IL-21 producing T cells than controls (P < .001). KTR and patients with CKD showed lower numbers of SARS-CoV-2–specific IgG–producing memory B cells when compared with controls (P < .001 and P = .01, respectively). The T-cell IL-21 response was positively associated with the SARS-CoV-2–specific B cell response and the SARS-CoV-2 spike S1–specific IgG antibody levels (both Pearson r = 0.5; P < .001). In addition, SARS-CoV-2–specific B cell responses were shown to be IL-21 dependent. Taken together, we show that IL-21 signaling is important in eliciting robust B cell–mediated immune responses in patients with kidney disease and KTR.

Healthy individuals with hybrid immunity, due to a SARS-CoV-2 infection prior to first vaccination, have stronger immune responses compared to those who were exclusively vaccinated. However, little is known about the characteristics of antibody, B- and T-cell responses in kidney disease patients with hybrid immunity. Here, we explored differences between kidney disease patients and controls with hybrid immunity after asymptomatic or mild coronavirus disease-2019 (COVID-19). We studied the kinetics, magnitude, breadth and phenotype of SARS-CoV-2-specific immune responses against primary mRNA-1273 vaccination in patients with chronic kidney disease or on dialysis, kidney transplant recipients, and controls with hybrid immunity. Although vaccination alone is less immunogenic in kidney disease patients, mRNA-1273 induced a robust immune response in patients with prior SARS-CoV-2 infection. In contrast, kidney disease patients with hybrid immunity develop SARS-CoV-2 antibody, B- and T-cell responses that are equally strong or stronger than controls. Phenotypic analysis showed that Spike (S)-specific B-cells varied between groups in lymph node-homing and memory phenotypes, yet S-specific T-cell responses were phenotypically consistent across groups. The heterogeneity amongst immune responses in hybrid immune kidney patients warrants further studies in larger cohorts to unravel markers of long-term protection that can be used for the design of targeted vaccine regimens.

Background.: Insight into cellular immune responses to COVID-19 vaccinations is crucial for optimizing booster programs in kidney transplant recipients (KTRs). Methods.: In an immunologic substudy of a multicenter randomized controlled trial (NCT05030974) investigating different repeated vaccination strategies in KTR who showed poor serological responses after 2 or 3 doses of an messenger RNA (mRNA)-based vaccine, we compared SARS-CoV-2-specific interleukin-21 memory T-cell and B-cell responses by enzyme-linked immunosorbent spot (ELISpot) assays and serum IgG antibody levels. Patients were randomized to receive: a single dose of mRNA-1273 (100 μg, n = 25), a double dose of mRNA-1273 (2 × 100 μg, n = 25), or a single dose of adenovirus type 26 encoding the SARS-CoV-2 spike glycoprotein (Ad26.COV2.S) (n = 25). In parallel, we also examined responses in 50 KTR receiving 100 μg mRNA-1273, randomized to continue (n = 25) or discontinue (n = 25) mycophenolate mofetil/mycophenolic acid. As a reference, the data were compared with KTR who received 2 primary mRNA-1273 vaccinations. Results.: Repeated vaccination increased the seroconversion rate from 21% to 66% in all patients, which was strongly associated with enhanced levels of SARS-CoV-2-specific interleukin-21 memory T cells (odd ratio, 3.84 [1.89-7.78]; P < 0.001) and B cells (odd ratio, 35.93 [6.94-186.04]; P < 0.001). There were no significant differences observed in these responses among various vaccination strategies. In contrast to KTR vaccinated with 2 primary vaccinations, the number of antigen-specific memory B cells demonstrated potential for classifying seroconversion after repeated vaccination (area under the curve, 0.64; 95% confidence interval, 0.37-0.90; P = 0.26 and area under the curve, 0.95; confidence interval, 0.87-0.97; P < 0.0001, respectively). Conclusions.: Our study emphasizes the importance of virus-specific memory T- and B-cell responses for comprehensive understanding of COVID-19 vaccine efficacy among KTR.

Background: Vaccine immunogenicity is reduced in kidney transplant recipients (KTRs), especially in those using mycophenolate mofetil (MMF). Whether replacement of MMF by everolimus improves vaccine immunogenicity is unknown. Methods: KTRs were randomized 1:1 to continue MMF or switch to everolimus. Participants received one coronavirus disease 2019 (COVID-19) booster vaccination and two herpes zoster (HZ) vaccinations at 6, 10 and 14 weeks postrandomization. Primary outcome was the neutralizing antibody response 28 days after COVID-19 vaccination. Secondary outcomes included antibody and T-cell responses 28 days after COVID-19 and HZ vaccination, and safety. Results: In 110 KTRs, COVID-19 vaccination resulted in comparable Omicron XBB.1.5 neutralizing antibody titers in the everolimus versus MMF group (308 [74.4–1314] vs 327 [115–897]; P = .83), whereas severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Spike-specific T-cell responses were slightly lower with everolimus (118 [32.1–243] vs 228 [113–381] spot-forming cells [SFCs]/106 peripheral blood mononuclear cells [PBMCs]; P = .02). HZ vaccination led to higher varicella zoster virus (VZV) glycoprotein E (gE)–specific immunoglobulin G titers with everolimus (2192 [888–4523] vs 1101 [440–2078] 50% endpoint titer; P = .004), while VZV gE-specific T-cell responses were similar (85.0 [27.5–155] vs 115 [50.0–258] SFCs/106 PBMCs; P = .24). Besides known side effects, everolimus led to more bacterial infections (27.3% vs 11.1%; P = .03). Conclusions: Six weeks’ replacement of MMF by everolimus in KTRs does not improve COVID-19 booster vaccine immunogenicity, whereas 10 weeks’ replacement enhances humoral HZ vaccine immunogenicity. While replacing MMF by everolimus may improve vaccine responses, its timing and potential risks require careful consideration.