Dynamics of Humoral and Cellular Responses in Renal Transplant Recipients Receiving 3 Doses of SARS-CoV-2 mRNA Vaccine.

BACKGROUND: The original SARS-CoV-2 vaccination regimen (2 doses) induces insufficient short-term response in kidney transplant (KT) recipients. This study assessed the response to a third dose and the long-term immunogenicity after 2 doses in KT. METHODS: We analyzed the dynamics of the humoral and cellular response by monitoring SARS-CoV-2 IgG antibodies against the Spike-protein (IgG-Spike) and QuantiFERON SARS-CoV-2 IFN-γ release assay 6 mo after the second dose (T2) and 28 d after the third dose of mRNA vaccines (T3) to KT and controls (dialysis patients and healthy individuals). RESULTS: At T2, the percentage of IgG-Spike+ KT and dialysis patients decreased (KT 65.8%-52.6%, hemodialysis 92.6-81.5%, and peritoneal dialysis 100%-90%), whereas 100% of healthy controls remained positive. About the cellular response, the percentage of responders decreased in all groups, especially in KT (22.4%-9.2%, P = 0.081). At T3, 92% of KT, 94%-98% of dialysis patients, and 100% of healthy controls were IgG-Spike+. In terms of antibody titers, patients and controls showed a reduction between T2 and T3 and about 80% of dialysis patients and 100% of controls achieved high titers after the third dose (>1479.5 Binding Antibody Units/mL), whereas this percentage was only 50% in KT. With respect to the cellular response, only KT displayed a significant rise after the third dose. CONCLUSIONS: The third dose of mRNA vaccine improves both humoral and cellular responses, but less effectively in KT compared with dialysis patients and healthy controls.

Impact of DE Novo Immunosuppression in The Covid-19 Serological Status at Kidney Transplantation

BACKGROUND AND AIMS COVID-19 infection has heavily impacted our national health system since March-2020. Although the kidney transplant (KT) activity was strongly reduced initially, nowadays it is partially recovered by using ‘COVID-clean’ pathways and vaccination of KT candidates since February-2021. However, scarce information is available regarding how de novo KT immunosuppression influences the serological status of vaccinated recipients. METHOD We reviewed the course of 38 de novo KT recipients transplanted between March-September 2021 fully vaccinated before KT. SARS-CoV-2 IgG antibodies against Spike (IgG-S) before and after KT (median: 32 days) were quantified with a serological assay (positive ≥13.0 AU/mL). RESULTS Of 38 recipients, 35 showed positive IgG-S at KT (92%). We exclude from the analysis, 4 recipients with COVID infection which interfered the analysis and 5 with inappropriate samples. The remaining 26 recipients had received the second dose of the mRNA vaccine a median time of 48 days before the pre-KT IgG determination. All patients maintained IgG-S over the cut-off after KT, but we observed that half de novo recipients (53.8%) showed a 50% reduction in the level of IgG-S at 1 month: 12/20 (60%) of those who received induction with basiliximab and 2/6 (33%) who received thymoglobulin. Regarding the impact of maintenance immunosuppression under induction with basiliximab, the IgG-S levels halved in 50% of those with tacrolimus-mycophenolate and 67% with tacrolimus-everolimus. The restricted analysis of IgG-S levels excluding five outliers before KT (>800 AU/mL) showed the most intense reduction in three KT recipients who received thymoglobulin-tacrolimus- mycophenolate (263.8 versus 68.8, 74%) compared with seven basiliximab-tacrolimus-mycophenolate cases (494.4 versus 359.8, 27%) and eleven basiliximab-tacrolimus-everolimus (344.0 versus 306.4, 11%) KT recipients. CONCLUSION Immunosuppression in de novo KT recipients reduces significantly the seroprotective levels of antibodies anti-Spike induced by COVID m-RNA vaccines in more than half the recipients. In our experience, the combination of thymoglobulin, tacrolimus and mycophenolate produces a more intense reduction than the combination of basiliximab with tacrolimus and mycophenolate or everolimus.

Covid-19 Infection After Kidney Transplantation in Spain: Comparable Impact Throughout Six Epidemic Waves

BACKGROUND AND AIMS The successive COVID-19 epidemic waves have significantly influenced kidney transplantation (KT) programs. Contact protection together with vaccination are the principal protective tools for KT recipients. We reviewed the impact of COVID-19 infection in KT recipients throughout the different epidemic waves. METHOD Of 900 active KT recipients in our program, 160 (17.8%) have suffered COVID-19 infection during the six epidemic waves: first (March–August 2020), second (September–December2020), third (January–March 2021), fourth (April–May 2021), fifth (June–September 2021) and sixth (October–December 2021, preliminary data). We compared the clinical evolution and the impact of vaccination. RESULTS Infected KT recipients were younger in the third and fourth waves (P  < 0.001). We observed a higher percentage of pneumonia and hospital admission in the first and fifth waves (P = 0.045, P = 0.016) (Table 1), without differences in ICU admission, and with the disappearance of asymptomatic cases after the third wave. The highest mortality was observed in KT recipients >65 years old infected within the first 6 months after KT (P = 0.006) and overall mortality was higher in the first wave (P = 0.033). Mortality in hospitalized KT recipients and those admitted in the ICU were similar along the 5 waves, without clear impact of vaccination (P = 0.251). On the 5 January 2022, we have already accumulated an incidence of COVID in KT of 3.1% (sixth wave, 77% with booster vaccination), similar to the first wave (3.8%), with 12.5% mortality, similar to second, third and fifth waves, in patients with outcome (53.3%). CONCLUSION The incidence of COVID-19 in KT recipients has been high in all the waves of the pandemic in Spain. Global mortality has diminished after the first wave, and the time until outcome has increased. The highest mortality occurs in the subgroup of old KT recipients early after KT. Vaccination has not significantly reduced the mortality in KT with Covid who require hospital or ICU admission.

Use and Safety of Remdesivir in Kidney Transplant Recipients With COVID-19.

INTRODUCTION: Remdesivir has demonstrated antiviral activity against coronavirus, shortening the time to recovery in adults hospitalized with moderate/severe COVID-19. Severe adverse events such as acute kidney injury have been reported. Scant data are available on the use and safety of remdesivir in kidney transplant recipients. METHODS: We present a multicenter cohort study of 51 kidney transplant recipients with COVID-19 treated with remdesivir. Outcomes and safety were assessed. RESULTS: Mean age at diagnosis was 60 years, with a median time since kidney transplant of 4.5 years. Mean time since admission to remdesivir was 2 days. Twenty-eight patients (54.9%) required mechanical ventilation (19 noninvasive). Mortality was 18.9% and markedly higher if aged ≥65 years (45% vs. 3.2% in younger patients). Acute kidney injury was present in 27.7% of patients, but was diagnosed in 50% before treatment. No patients required remdesivir discontinuation because of adverse events. We did not find significant hepatoxicity or systemic symptoms resulting from the drug. CONCLUSION: In our cohort of kidney transplant recipients, remdesivir was well tolerated and safe in renal and hepatic toxicity, but randomized trials are needed to assess its efficacy.

Clinical Profiles in Renal Patients with COVID-19.

The COVID-19 pandemic has led to frequent referrals to the emergency department on suspicion of this infection in maintenance hemodialysis (MHD) and kidney transplant (KT) patients. We aimed to describe their clinical features comparing confirmed and suspected non-confirmed COVID-19 cases during the Spanish epidemic peak. Confirmed COVID-19 ((+)COVID-19) corresponds to patient with positive RT-PCR SARS-CoV-2 assay. Non-confirmed COVID-19 ((-)COVID-19) corresponds to patients with negative RT-PCR. COVID-19 was suspected in 61 patients (40/803 KT (4.9%), 21/220 MHD (9.5%)). Prevalence of (+)COVID-19 was 3.2% in KT and 3.6% in MHD patients. Thirty-four (26 KT and 8 MHD) were (+)COVID-19 and 27 (14 KT and 13 MHD) (-)COVID-19. In comparison with (-)COVID-19 patients, (+)COVID-19 showed higher frequency of typical viral symptoms (cough, dyspnea, asthenia and myalgias), pneumonia (88.2% vs. 14.3%) and LDH and CRP while lower phosphate levels, need of hospital admission (100% vs. 63%), use of non-invasive mechanical ventilation (36% vs. 11%) and mortality (38% vs. 0%) (p < 0.001). Time from symptoms onset to admission was longer in patients who finally died than in survivors (8.5 vs. 3.8, p = 0.007). In KT and MHD patients, (+)COVID-19 shows more clinical severity than suspected non-confirmed cases. Prompt RT-PCR is mandatory to confirm COVID-19 diagnosis.

COVID-19 in elderly kidney transplant recipients.

The SARS-Cov-2 infection disease (COVID-19) pandemic has posed at risk the kidney transplant (KT) population, particularly the elderly recipients. From March 12 until April 4, 2020, we diagnosed COVID-19 in 16 of our 324 KT patients aged ≥65 years old (4.9%). Many of them had had contact with healthcare facilities in the month prior to infection. Median time of symptom onset to admission was 7 days. All presented with fever and all but one with pneumonia. Up to 33% showed renal graft dysfunction. At infection diagnosis, mTOR inhibitors or mycophenolate were withdrawn. Tacrolimus was withdrawn in 70%. The main treatment combination was hydroxychloroquine and azithromycin. A subset of patients was treated with anti-retroviral and tocilizumab. Short-term fatality rate was 50% at a median time since admission of 3 days. Those who died were more frequently obese, frail, and had underlying heart disease. Although a higher respiratory rate was observed at admission in nonsurvivors, symptoms at presentation were similar between both groups. Patients who died were more anemic, lymphopenic, and showed higher D-dimer, C-reactive protein, and IL-6 at their first tests. COVID-19 is frequent among the elderly KT population and associates a very early and high mortality rate.