Treatment with sotrovimab for SARS-CoV-2 infection in a cohort of high-risk kidney transplant recipients.

Background: Sotrovimab is a neutralizing monoclonal antibody (mAb) that seems to remain active against recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. The evidence on its use in kidney transplant (KT) recipients, however, is limited. Methods: We performed a multicenter, retrospective cohort study of 82 KT patients with SARS-CoV-2 infection {coronavirus disease 2019 [COVID-19]} treated with sotrovimab. Results: Median age was 63 years. Diabetes was present in 43.9% of patients, and obesity in 32.9% of patients; 48.8% of patients had an estimated glomerular filtration rate under 30 mL/minute/1.73 m2. Additional anti-COVID-19 therapies were administered to 56 patients, especially intravenous steroids (65.9%). Sotrovimab was administered early (<5 days from the onset of the symptoms) in 46 patients (56%). Early-treated patients showed less likely progression to severe COVID-19 than those treated later, represented as a lower need for ventilator support (2.2% vs 36.1%; P < .001) or intensive care admission (2.2% vs 25%; P = .002) and COVID-19-related mortality (2.2% vs 16.7%; P = .020). In the multivariable analysis, controlling for baseline risk factors to severe COVID-19 in KT recipients, early use of sotrovimab remained as a protective factor for a composite outcome, including need for ventilator support, intensive care, and COVID-19-related mortality. No anaphylactic reactions, acute rejection episodes, impaired kidney function events, or non-kidney side effects related to sotrovimab were observed. Conclusions: Sotrovimab had an excellent safety profile, even in high-comorbidity patients and advanced chronic kidney disease stages. Earlier administration could prevent progression to severe disease, while clinical outcomes were poor in patients treated later. Larger controlled studies enrolling KT recipients are warranted to elucidate the true efficacy of monoclonal antibody therapies.

Treatment with sotrovimab for SARS-CoV-2 infection in a cohort of high-risk kidney transplant recipients

Background Sotrovimab is a neutralizing monoclonal antibody (MAB) which seems to remain active against recent SARS-CoV-2 variants. However, the evidence on its use in kidney transplant (KT) recipients is limited. Methods We performed a multicenter retrospective cohort study of 82 KT patients with SARS-CoV-2 infection (COVID-19) treated with sotrovimab. Results Median age was 63 years. Diabetes was present in 43.9%, obesity in 32.9% and 48.8% of patients had an estimated Glomerular Filtration Rate <30 mL/min/1.73m2. Additional anti-COVID-19 therapies were administered in 56 patients, especially intravenous steroids (65.9%). Sotrovimab was administered early (<5 days from the onset of the symptoms) in 46 patients (56%). Early-treated patients showed less likely progression to severe COVID-19 than those treated later, represented as a lower need for ventilator support (2.2% vs. 36.1%, P<0.001) or intensive care admission (2.2% vs. 25%;P = 0.002) and COVID-19-related mortality (2.2% vs. 16.7%;P = 0.020). In the multivariable analysis, controlling for baseline risk factors to severe COVID-19 in KT recipients, early use of sotrovimab remained as a protective factor for a composite outcome including need for ventilator support, intensive care and/or COVID-19-related mortality. No anaphylactic reactions, acute rejection episodes, impaired renal function events or non-renal side effects related to sotrovimab were observed. Conclusions Sotrovimab had an excellent safety profile even in high-comorbidity patients and advanced chronic kidney disease stages. Earlier administration could prevent progression to severe disease while clinical outcomes were poor in patients treated later. Larger controlled studies enrolling KT recipients are warranted to elucidate the true efficacy of MAB therapies. Graphical Graphical

Manejo de la inmunosupresión en pacientes trasplantados de riñón con COVID19. Estudio multicéntrico nacional derivado del registro COVID de la S.E.N Management of immunosuppressive therapy in kidney transplant recipients with COVID19. A multicentre national study derived form the S.E.N. COVID registry

Introducción: La infección por SARS CoV2 ha impactado de forma importante en los pacientes con trasplante renal causando una elevada mortalidad en los primeros meses de la pandemia. La reducción intencionada de la inmunosupresión se ha postulado como uno de los pilares en el manejo de la infección ante la falta de un tratamiento antiviral dirigido. Ésta se ha modificado de acuerdo con la situación clínica de los pacientes y su efecto sobre la función renal o los anticuerpos anti-HLA a medio plazo no ha sido evaluado. Objetivos: Evaluar los cambios de inmunosupresión realizados durante la infección por SARS-CoV2, así como la función renal y los anticuerpos anti-HLA de los pacientes trasplantados de riñón a los 6 meses del diagnóstico de COVID19. Material y métodos: Estudio retrospectivo, multicéntrico nacional (30 centros) de pacientes trasplantados de riñón con COVID19 desde el 01/02/20 al 31/12/20. Se recogieron las variables de la historia clínica y se incluyeron en una base de datos anonimizada. Se utilizó el programa estadístico SPSS para el análisis de resultados. Resultados: Se incluyeron 615 trasplantados renales con COVID19 (62.6% varones), con una edad media de 57.5 años. El tratamiento inmunosupresor predominante antes del COVID19 era la triple terapia con prednisona, tacrolimus y ácido micofenólico (54.6%) seguido de los regímenes con inbidores m-TOR (18.6%). Tras el diagnóstico de la infección se suspendió el ácido micofenólico en el 73.8% de los pacientes, el inhibidor m-TOR en el 41.4%, tacrolimus en el 10.5% y ciclosporina A en el 10%. A su vez, el 26.9% recibieron dexametasona y al 50.9% se les inició o aumentó la dosis de prednisona basal. La creatinina media antes del diagnóstico de COVID19, en el momento del diagnóstico y a los 6 meses fue de: 1,7±0,8;2.1±1.2 y 1,8±1 mg/dl respectivamente (p<0,001). Al 56.9% de los pacientes (N=350) se les monitorizó los anticuerpos anti-HLA. El 94% (N=329) no presentaron cambios en los anti-HLA, mientras que el 6% (N=21) los positivizaron. De entre los pacientes con anticuerpos donante-específicos post-COVID19 (N=9), a 7 pacientes (3,1%) se les había suspendido un inmunosupresor (en cinco de ellos se suspendió ácido micofenólico y en 2 tacrolimus), a 1 paciente los 2 inmunosupresores (3,4%) y al otro paciente no se le había modificado la inmunosupresión (1,1%), siendo estas diferencias no significativas. Conclusiones: El manejo de la inmunosupresión tras el diagnóstico de COVID19 se basó fundamentalmente en la suspensión de ácido micofenólico con reducciones o suspensiones muy discretas de inhibidores de calcineurina. Este manejo de la inmunosupresión no influyó en la función renal ni en cambios de los anticuerpos anti-HLA a los 6 meses del diagnóstico.

Breakthrough Infections Following mRNA SARS-CoV-2 Vaccination in Kidney Transplant Recipients.

BACKGROUND: The clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in kidney transplant (KT) recipients is lower than in the general population. METHODS: From April to October 2021, 481 KT recipients with COVID-19, included in the Spanish Society of Nephrology COVID-19 Registry, were analyzed. Data regarding vaccination status and vaccine type were collected, and outcomes of unvaccinated or partially vaccinated patients (n = 130) were compared with fully vaccinated patients (n = 351). RESULTS: 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 = 0.776). In multivariable analysis, age and pneumonia were independent risk factors for death, whereas 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 (n = 213) showed a significantly lower mortality than those who received the BNT162b2 vaccine (n = 121) (hazard ratio: 0.52; 95% confidence interval, 0.31-0.85; P = 0.010). CONCLUSIONS: COVID-19 severity in KT patients has remained high and has not improved despite receiving 2 doses of the mRNA vaccine. The mRNA-1273 vaccine shows higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infections. Confirmation of these data will require further research taking into account the new variants and the administration of successive vaccine doses.