Comprehensive Assessment of Eyes in Kidney Transplant Recipients after Recovering from COVID-19.

INTRODUCTION: Patients after organ transplantation with COVID-19 have a higher risk of morbidity and mortality than patients in the general population. There are single studies that assess the eyes of COVID-19 patients, but there are no such studies on organ transplant recipients. The purpose of this study was to comprehensively examine the eyes of kidney transplant recipients (KTR) after recovery from mild to moderate SARS-CoV-2 infection. METHODS: A total of 40 KTR after COVID-19 and 20 KTR without clinical and immunological symptoms of SARS-CoV-2 infection as a control group was qualified for the cross-sectional study. A total of 76 eyes from 38 KTR on an average of 7 weeks after COVID-19 and 36 eyes from 18 KTR from the control group were studied. The participants underwent an ophthalmological examination, and the retinal and choroid vessels and nerves were assessed by optical coherence tomography angiography. RESULTS: We found a lower vessel density (VD) in the deep capillary plexus in the central part of the retina (VD deep central) of the study group. Women had significantly lower VD deep central in the study group (15.51 vs. 18.91, p < 0.001). Multivariate linear regression analysis confirmed an independent, negative impact of COVID-19 (p < 0.001) and female gender (p = 0.001) on VD deep central. CONCLUSION: The results of our study confirmed that changes in microcirculation induced by SARS-CoV-2 infection may affect the retinal vessels in KTR. Mild to moderate COVID-19 in KTR resulted in a significant reduction in VD deep central of the retina, with these changes being more common in females.

Effect of COVID-19 on Kidney Graft Function One Year after Onset.

Background and Objectives: Kidney transplant recipients (KTRs) are at a higher risk of severe COVID-19 development. The course of the infection may vary. Long-term consequences for graft function are still being studied. We investigate whether the clinical course of SARS-CoV-2 infection among KTRs had a long-term effect on graft function. Patients and method: 128 KTRs with confirmed SARS-CoV-2 infection were included in the study. They were divided into two groups: mild (without the need for oxygen therapy; n = 91) and severe (with the need for oxygen therapy; n = 21). Baseline characteristics and medical data, especially creatinine level, estimated glomerular filtration rate (eGFR) CKD-EPI, and proteinuria, were analyzed. The main outcomes were the absolute and relative change in eGFR during the one-year follow-up after COVID-19. In the final models, sex, age, smoking, presence of diabetes mellitus (DM), and cardiovascular disease (CVD) were included. Results: KTRs with severe COVID-19 were older, more likely to smoke, and had DM and CVD more frequently. Our analysis reveals that COVID-19 severity was associated with a significantly more pronounced relative eGFR decline one year after recovery only in males [-13.94 (95% CI: -25.13 to -2.76, p = 0.015) percentage points]. One year after the disease onset, males with a severe course of the infection had a higher eGFR decline than those with a mild one. The COVID-19 severity did not affect eGFR loss in females. Conclusions: In KTRs suffering from COVID-19, deterioration of graft function was noticed. The eGFR decline was associated with disease severity and sex. It indicates a need for further research, observation, and preventive actions for KTRs, especially males.

Safety and Tolerability of mRNA COVID-19 Vaccines in Kidney Transplant Recipients.

BACKGROUND: COVID-19 mRNA vaccines have demonstrated excellent short-term safety in phase 3 trials. However, no kidney transplant recipients (KTR) were included. The aim of the study was to assess the safety and tolerability of COVID-19 mRNA vaccines in KTR. MATERIALS AND METHODS: A longitudinal controlled study was conducted in 300 KTR and 143 control patients (CRL) without chronic kidney disease who had received 2-dose vaccinations with the mRNA vaccine. Solicited local and systemic reactogenicity and unsolicited adverse events were assessed with a standardized questionnaire. The toxicity grading scales were derived from the FDA guidelines. RESULTS: KTR (62.7% men) with a median (interquartile range) age of 53 (41-63) and transplant vintage of 7.25 (3-13) years did not differ with respect to age and sex distribution from CRL. One hundred percent CRL and 83.3% KTR were vaccinated with BNT162b2 (BionTech/Pfizer); 16.7% KTR received mRNA-1273 (Moderna) vaccine. Any local reactions were present in 84.7% (first dose) and 65.3% (second dose) KTR vs 67.1% and 60.1% CRL within 7 days after the vaccination. Any systemic reactions were reported by 26.7% (first dose) and 20.9% (second dose) KTR vs 24.7 and 35.7% CRL. The most common systemic reactions in KTR were fatigue, headache and myalgia. No serious adverse events were observed. Many systemic reactions were observed less frequently in KTR than CRL. Younger KTR (<54 years) reported any local and any systemic reactions significantly more frequently than older patients. CONCLUSION: mRNA COVID-19 vaccines are safe and well-tolerated by KTR. The results may resolve patients' doubts and reduce their vaccine hesitancy.

Local and Systemic Immunity Are Impaired in End-Stage-Renal-Disease Patients Treated With Hemodialysis, Peritoneal Dialysis and Kidney Transplant Recipients Immunized With BNT162b2 Pfizer-BioNTech SARS-CoV-2 Vaccine.

Vaccination against COVID-19 in patients with end-stage renal disease (ESRD) on replacement therapy and kidney transplant recipients (KTRs) is particularly important due to the high mortality rate. Here, we tested the local and systemic immunity to the novel Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) in ESRD, KTR patients, and healthy individuals (150 subjects). The ESRD group was divided into: hemodialysis (HD) and peritoneal dialysis (PD). We investigated the local and systemic immunity based on anti-N (nucleoprotein) and anti-S (spike1/2) Immunoglobulin A (IgA) and Immunoglobulin G (IgG) antibodies, respectively. Additionally, we performed an Interferon gamma (IFN-γ) release test Interferon-gamma release assay (IGRA) to monitor the cellular component of vaccine response. The control group had the highest level of anti-S IgG antibodies (153/2,080 binding antibody units (BAU)/ml) among all analyzed patients after the 1st and 2nd dose, respectively. The HD group (48/926 BAU/ml) had a diminished antibody level compared to PD (93/1,607 BAU/ml). Moreover, the seroconversion rate after the 1st dose was lower in HD than PD (56% vs. 86%). KTRs had extremely low seroconversion (33%). IgA-mediated immunity was the most effective in the control group, while other patients had diminished IgA production. We observed a lower percentage of vaccine responders based on the IFN-γ level in all research participants (100% vs. 85% in control, 100% vs. 80% in PD, 97% vs. 64% in HD). 63% of seropositive KTRs had a positive IGRA, while 28% of seronegative patients produced IFN-γ. Collectively, PD patients had the strongest response among ESRD patients. Two doses of the Pfizer vaccine are ineffective, especially in HD and KTRs. A closer investigation of ESRD and KTRs is required to set the COVID-19 vaccine clinical guidance. Clinical Trial Registration Number: www.ClinicalTrials.gov, identifier: NCT04 905 862.

Heterologous high dose SARS-CoV-2 mRNA vaccine booster may improve immune response in seronegative kidney transplant recipients.

Introduction: Three-dose mRNA vaccination against COVID-19 is unable to elicit a sufficient immune response in immunocompromised subjects. Methods: The aim of the study was to conduct a retrospective evaluation of the efficacy of a heterologous mRNA booster with mRNA-1273 in constantly seronegative kidney transplant recipients (KTRs) after three doses of the BNT162b2 mRNA vaccine. Twelve seronegative KTRs received a mRNA-1273 booster 5 months after the third dose of BNT162b2. Results: A total of 5 out of 12 patients (41.7%) seroconverted, with a mean titer of 353 BAU/ml. Conclusions: The administration of a heterologous mRNA vaccine as a booster may be an effective alternative for achieving post-vaccination immunity in seronegative KTRs.

Changes in Kidney Graft Function in COVID-19 Convalescents.

BACKGROUND: Kidney transplant recipients (KTRs) are at an increased risk of infection with severe acute respiratory syndrome coronavirus 2, with mortality from 13% to over 30%. However, data concerning the influence of COVID-19 on long-term graft function in convalescents is lacking. The aim of this study was to evaluate the influence of COVID-19 on graft function at 6 months after recovery. METHODS: A longitudinal controlled study was conducted in a group of 1058 KTRs. Of 180 patients with COVID-19 in the past, 77 KTRs (45 male) with a mean age 50.57 ± 13.37 years, Charlson Comorbidity Index of 3 (median; interquartile range [IQR], 3-5), Fragility Score of 3 (median; IQR, 3-3), and minimum 6 months after acute COVID-19 were included. The most common symptoms were weakness (75.33%), fever (74.03%), cough (51.95%), and loss of appetite (48.05%). Thirty-three patients were hospitalized; none required invasive ventilation therapy, but 16 required oxygen support. The treatment of COVID-19 included antibiotics (38.96%), thromboprophylaxis (25.97%), and nonsteroidal anti-inflammatory drugs, or paracetamol (25.97%). RESULTS: The median (IQR) values of serum creatinine 3 months before the onset and 6 months after COVID-19 were 1.25 (0.98-1.86) and 1.26 (1.03-1.78) mg/dL (nonsignificant difference); in strata analysis, there were also no differences with regards to patients with higher and lower comorbidity (3 < Charlson Comorbidity Index < 3) and fragility (3 < Fragility Score < 3). Furthermore, creatinine concentration in KTRs and controls did not differ. CONCLUSIONS: In the group of KTRs with a mild course of COVID-19, no negative impact of the infection on graft function was observed 6 months after transplantation.

Post-COVID-19 Sydrome and Decrease in Health-Related Quality of Life in Kidney Transplant Recipients after SARS-COV-2 Infection-A Cohort Longitudinal Study from the North of Poland.

INTRODUCTION: Patients after SARS-CoV-2 infection frequently face "Post-COVID-19 Syndrome", defined by symptoms that develop during or after COVID-19, continue for more than 12 weeks, and are not explained by an alternative diagnosis. We aimed to evaluate the presence of post-COVID-19 syndrome and its predictors in kidney transplant recipients (KTR) 6 months after the disease. MATERIALS AND METHODS: A total of 67 KTR (38 m) with a mean age of 53.6 ± 14 years, 7.3 ± 6.4 years post-transplant were included in the cohort longitudinal study. Thirty-nine (58.2%) of them were hospitalized, but not one required invasive ventilation therapy. They were interviewed 6 months after being infected, with a series of standardized questionnaires: a self-reported symptoms questionnaire, the modified British Medical Research Council (mMRC) dyspnea scale, EQ-5D-5L questionnaire, and EQ-VAS scale. RESULTS: Post-COVID-19 syndrome was diagnosed in 70.1% of KTR and 26.9% of them reported at least three persistent symptoms. The most common symptoms were fatigue (43.3%), hair loss (31.3%), memory impairment (11.9%), muscle aches, and headaches (11.9%). Dyspnea with an mMRC scale grade of at least 1 was reported by 34.3% patients vs. 14.9% before infection; 47.8% stated that they still feel worse than before the disease. Mean EQ-VAS scores were 64.83 vs. 73.34 before infection. The persistent symptoms are more frequent in older patients and those with greater comorbidity. CONCLUSIONS: Persistent symptoms of post-COVID-19 syndrome are present in the majority of KTR, which highlights the need for long-term follow-up as well as diagnostic and rehabilitation programs.

Predictors of Humoral Response to mRNA COVID19 Vaccines in Kidney Transplant Recipients: A Longitudinal Study-The COViNEPH Project.

BACKGROUND: The efficacy of SARS-CoV-2 vaccination among kidney transplant recipients (KTR) is low. The main goal of this study was to analyze factors that may influence the humoral response to vaccination. METHODS: We analyzed the titer magnitude of IgG antibodies directed against spike (S)-SARS-CoV-2 antigen after the second dose of the mRNA vaccine in 142 infection naïve KTR (83 men, i.e., 58.4%) with a median age (IQR) of 54 (41-63), and 36 respective controls without chronic kidney disease. mRNA-1273 or BNT162b2 were applied in 26% and 74% of KTR, respectively. RESULTS: S-specific immune response (seroconversion) was seen in 73 (51.41%) of KTR, and in all controls 36 (100%). Independent predictors of no response were elder age, shorter transplantation vintage, and a more than two-drug immunosuppressive protocol. In subgroup analyses, the seroconversion rate was highest among KTR without MMF/MPS treatment (70%), treated with no more than two immunosuppressants (69.2%), treated without corticosteroid (66.7%), younger patients aged <54 years (63.2%), and those vaccinated with the mRNA-1273 vaccine (62.16%). The independent predictors of higher S-antibody titer among responders were younger age, treatment with no more than two immunosuppressants, and the mRNA-1273 vaccination. CONCLUSIONS: Our study confirmed a low rate of seroconversion after vaccination with the mRNA vaccine in KTR. The major modifiable determinants of humoral response were the composition of the immunosuppressive protocol, as well as the type of vaccine. The latter could be taken into consideration when initial vaccination as well as booster vaccination is considered in KTR.

Boosting Humoral Immunity from mRNA COVID-19 Vaccines in Kidney Transplant Recipients.

Introduction: The immune response to the primary (two-dose) series of mRNA COVID-19 vaccines in kidney transplant recipients (KTRs) is very weak. We conducted a longitudinal observational study to compare the humoral response to a third, additional primary dose of mRNA vaccines between infection-naïve (IN-KTRs) and previously infected KTRs (PI-KTRs). Methods: We measured the levels of anti-spike (anti-s) IgG antibodies before and 14-21 days after the third dose and, in the secondary analysis, we compared the antibody response to BNT162b2 versus mRNA-1273. The reactogenicity assessment included solicited local and systemic reactions. Results: A total of 112 KTRs were enrolled, including 83 IN-KTR and 29 PI-KTR, among whom seroconversion in anti-s antibodies after the primary two-dose vaccination was achieved in 45.78% and 100% of cases, respectively. After three months, a waning antibodies titer by 67.4% (IN-KTR) and 7.5% (PI-KTR) was observed. After the third dose of the mRNA vaccine, 71.08% (59/83) of IN-KTR and 96.5% (28/29) of PI-KTR samples were seroconverted with a median anti-s titer of 468.0 (195.0-1620.0) BAU/mL and 1629.0 (1205-1815) BAU/mL, respectively. Of those IN-KTR in whom the primary vaccination failed, 46.67% (21/45) of patients achieved seroconversion after the third dose. No serious adverse events after the third dose were reported. In strata analyses, after the third dose, 66% (40/60) of patients vaccinated with BNT162b2 and 82.6% (19/23) of patients vaccinated with mRNA-1273 seroconverted with a median anti-s titer of 384.5 (144-837) BAU/mL and 1620 (671-2040) BAU/mL, respectively. Conclusions: The use of a third dose of mRNA vaccine may be of benefit for KTR, especially for those in whom the primary vaccination failed. Vaccines with a higher dose of mRNA and a longer interval between doses of the primary vaccination, such as mRNA-1273, seem to be the preparations of choice in immunocompromised individuals.