Comparison of Outcomes of Covid-19 Between Fully Vaccinated and Unvaccinated Kidney Transplant Recipients and According to the Type of M-RNA Vaccine

Purpose: The evidence regarding the clinical effectiveness of COVID-19 vaccination in kidney transplant (KT) recipients is limited so far. Our purpose is to analyze the characteristics and outcomes of a large series of KT with COVID-19 breakthrough infection and compare them with unvaccinated patients. As a secondary objective, we analyzed the evolution according to the type of mRNA vaccine administered. Method(s): From April to October 2021, KT recipients with COVID-19, included in the COVID-19 registry of the Spanish Society of Nephrology, were analyzed. Data regarding vaccination status and type of vaccine were collected and outcomes of unvaccinated or partially vaccinated patients were compared with fully vaccinated patients. Result(s): Clinical picture was similar and survival analysis showed no differences between groups: 21.7% of fully vaccinated patients and 20.8% of unvaccinated or partially vaccinated died (p=.776). In multivariable analysis age and pneumonia were independent risk factors for death, while vaccination status was not related to mortality. These results remained similar when we excluded patients with partial vaccination as well as when we analyzed exclusively hospitalized patients. Patients vaccinated with mRNA-1273 (Moderna) (n=213) showed a significantly lower mortality than those who received BNT162b2 (Pfizer-BioNTech) vaccine (n=121) (16.4% vs. 28.8%, p=.002) (HR: 0.52, CI 95% 0.31-0.85, p=.010). Conclusion(s): COVID-19 severity in KT patients has remained high and has not improved despite receiving 2 doses of an mRNA vaccine, but the mRNA-1273 vaccine shows higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infection, so it could be considered as the first option in these patients.

HUMORAL RESPONSE AFTER SUCCESSIVE DOSES OF MRNA VACCINE AGAINST SARS-COV-2 IN STABLE KIDNEY TRANSPLANT RECIPIENTS

BACKGROUND AND AIMS: The poor humoral response after vaccination against SARS-CoV-2 in kidney transplant (KT) patients led to the approval of a third dose. Recent data show an increase in the antibody titer, although lower than in the general population. Our aim is to analyze the humoral immune response after the third dose a mRNA vaccine against SARS-CoV-2 and the evolution of the antispike antibody (antiS) titers in KT recipients. METHOD: We performed a prospective cohort study of stable KT patients from our center who received three doses of a mRNA vaccine from March to November 2021. KT recipients with less than 6 months after transplantation and with active oncological or hematologic disease were excluded. We determined antiS titers (Abbott SARS-CoV- 2 IgG chemiluminescent microparticle immunoassay) at baseline, one month after the second dose and one month after the third one. We compared those KT patients who seroconverted with 2 and with 3 doses of vaccine and those who did not seroconvert. To identify risk factors for no seroconversion, a logistic regression analysis was carried out. RESULTS: We included 83 KT. Mean age was 59.3 years and 62.7% were male. The median time from KT to the first vaccine dose was 94 months and between the second and third dose median time was 4 months. Seroconversion rate was 63.8% after 2 doses and 85.5% after the third one (P < 0.001). Twelve KT did not develop antibodies (Table 1). Patients who did not seroconvert were older (P = 0.047), had a worse renal function (P = 0.009) and had fewer lymphocytes than those that developed antibodies (0.013). Besides, they almost half of them received a KT from a non-heart-beating donor (P = 0.026) and were treated with thymoglobulin in the 2 years prior to the vaccine more frequently (P = 0.007). In patients who seroconverted after 2 doses, we observed a 10-fold increase in the antiS titer after the third vaccine (82 [34-350] UI/mL versus 814 [205-2415] UI/mL;P < 0.001). No patients had neither acute rejection nor serious adverse effects. In the multivariable analysis advanced age, a worse kidney function and recent treatment with thymoglobulin were risk factors for no seroconversion (Table 1). CONCLUSION: The third dose of a mRNA vaccine against SARS-CoV-2 significantly increased the seroconversion rate and the antiS titers in stable KT patients. Advanced age, poorer kidney function and immunosuppressive treatment are risk factors for no seroconversion. (Table Presented).

Acute Kidney Injury and Urinary and Histopathological Disorders in Kidney Transplant Patients with SARS-CoV-2 Infection.

BACKGROUND: Acute kidney injury (AKI) is a manifestation of SARS-CoV-2 infection. The evidence in kidney transplant (KT) is limited, as there are scarce data about the histologic features in graft biopsies of these patients. MATERIAL AND METHODS: A retrospective cohort study of KTs with SARS-CoV-2 infection from August 28, 2020, to April 23, 2021. We collected the incidence of AKI and the presence of urinary and histopathological disorders. Both groups were compared (AKI vs no AKI). Immunohistochemical and reverse transcription-polymerase chain reaction studies were performed on the anatomopathological samples. RESULTS: In our study, 72 KTs had SARS-CoV-2 infection and, among them, 27 patients (35.1%) developed AKI related to increased severity and a worse evolution of the infection, defined by a greater presence of pneumonia (P < .001), hospitalization (P < .001), admission to the intensive care unit (P < .001), the need for ventilation support (P < .001), and continuous renal replacement therapy (P < .001). In the multivariable analysis, pneumonia behaved as an independent predictor for AKI development (P = .046). No differences were observed between proteinuria a month before and after infection (P = .224). In addition, 5 patients showed microhematuria and 2 patients presented transient glycosuria without hyperglycemia. Of the 5 kidney biopsies performed, 1 biopsy (20%) showed positive reverse transcription polymerase chain reaction for SARS-CoV-2. CONCLUSIONS: AKI is a frequent and potentially serious complication in KT patients. Occasionally it could be accompanied by abnormalities in the urinary sediment. Of 5 biopsied patients, 1 patient had positive reverse transcription polymerase chain reaction in renal tissue, which suggests the systemic spread of the virus and the tropism for the renal graft.

Predictors of severe COVID-19 in kidney transplant recipients in the first and second waves: Analysis of the spanish registry

Purpose: To better know the impact and characteristics of Covid-19 in renal patients, the Spanish Society of Nephrology set up a voluntary registry in March, 2020 Methods: Retrospective observational study of KT recipients included in the Spanish Covid-19 Registry (1st March to 14th November, 2020). We applied Cox multivariate analysis to identify risk factors for mortality and Kaplan-Meier and log rank survival analysis. Results: 1080 KT with Covid-19 were registered, having 937 (86.1%) their outcome reported (cure or death). Most were men (63.2%), mean age 60 years infected a median of 72 months postransplantation. Death occurred in 204 patients. Multivariate analysis found age, neumonia and KT within the last 6 months before Covid-19 were risk factors for mortality and gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups: age<65 years&postransplant time> 6mo (n=526), age<65×<6mo (n=49), age>65× >6mo (n=325) and age>65×<6mo (n=31)($$graphic). Of 1080 cases, 605 correspond to the first wave (1stW until June2020) and 475 to the second wave (2ndW). In the 2ndW, KT were younger (56.4 vs 61.1yr;p=.000), 15.8% were asymptomatic (p=.000) and presented less pneumonia (50.3% vs. 78%;p=.000). Fever, lymphopenia and respiratory symptoms were less frequent but gastrointestinal symptoms similar (30.9% vs. 34.2%;p=.256). Treatment has changed, with more use of remdesivir (p=.000) and steroids (p=.018), no use of ritonavir/lopinavir, hidroxycloroquine andazitromycin (p=.000), and no treatment in (37.1% vs 6.3% in 1stW, p=.000). Hospitalization decreased (89.2% vs. 63.2%;p=.000) but more KT were admitted to critical care units (14.5% vs 20%;p=.058). We found lower mortality (overall 26.4% vs 14.8%;p=.000, hospitalized 29% vs 23%;p=.088). Multivariate analysis of the 2ndW shows again that age, pneumonia and recent transplant (< 6 months) are mortality risk factors. Conclusions: Over a thousand KT have suffered Covid-19 in Spain with a high mortality rate in the first and second waves, mainly related with age, pneumonia and recent transplantation. The interaction between age and time after transplant has to be considered when selecting recipients in the Covid-19 pandemic.