RESUMEN
Introduction: The efficacy of nirmatrelvir-ritonavir (NR; Paxlovid, Pfizer, New York, NY) to decrease the risk of progression to severe COVID-19 in high-risk patients has been demonstrated. However, evidence in infected kidney transplant recipients (KTRs) is lacking. Moreover, NR has significant and potentially harmful interactions with calcineurin inhibitors (CNIs). Methods: In this single-center retrospective study, we included all KTRs treated with NR from April 28 to June 3, 2022. A standard management strategy of CNI dose adaptation (discontinuation of tacrolimus 12 hours before the start of NR and administration of 20% of the cyclosporine dose) and laboratory follow-up was applied. Results: A total of 14 patients were included. Compared with day-0 (day before NR initiation), day-7 plasma creatinine concentrations and SARS-CoV-2 viral loads were similar (P = 0.866) and decreased (P = 0.002), respectively. CNI trough concentrations at the end of the treatment were satisfactory, nonetheless, with high individual variability. After a median follow-up time of 34 days, no death or viral pneumonia were observed. Nevertheless, 2 patients experienced early SARS-CoV-2 infection relapses (at day-10 and day-21) associated with an increase in SARS-CoV-2 viral loads. Conclusion: NR can be used in KTRs but requires a strict protocol of drug adaptation. We observed 2 cases of early relapse after NR treatment that need further investigations.
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COVID-19/inmunología , Inmunidad Humoral/efectos de los fármacos , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , SARS-CoV-2/inmunología , Adulto , Anciano , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacuna BNT162 , Bélgica , COVID-19/sangre , COVID-19/prevención & control , COVID-19/virología , Vacunas contra la COVID-19/administración & dosificación , ChAdOx1 nCoV-19 , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Rationale & Objective: Neutralizing monoclonal antibody treatments have shown promising preliminary results in kidney transplant recipients infected with severe acute respiratory syndrome coronavirus 2. However, their efficacy in kidney transplant recipients infected with the Omicron variant has not been reported yet. Study Design: Single-center retrospective study. Setting & Participants: We included all consecutive kidney transplant recipients treated with monoclonal antibodies for severe acute respiratory syndrome coronavirus 2 infections (positive polymerase chain reaction on nasopharyngeal swab) between June 10, 2021, and January 14, 2022. Forty-seven kidney transplant recipients were included. All patients had symptoms evolving for ≤7 days and no oxygen therapy need at monoclonal antibody infusion. Results: Symptoms at diagnosis were mainly cough (n = 25; 53%) and fever (n = 15; 32%). Eighty-three percent of the cohort (n = 39) had been vaccinated with at least 2 doses before infection, of whom 30 (77%) had demonstrated a vaccine-induced humoral response. They were treated with either casirivimab-imdevimab (n = 16; 34%) or sotrovimab (n = 31; 66%) a median of 2 days (range, 0-6 days) after the onset of symptoms. Except for 1 mild allergic reaction during casirivimab-imdevimab infusion, no side effects were reported. The median viral loads at admission (day 0) and 7 days after monoclonal antibody infusion were 2,110,027 copies/mL (range, 1,000-153,798,962 copies/mL) and 1,000 copies/mL (range, 0-10,000,000 copies/mL), respectively. Genotypes were available for 22 kidney transplant recipients (47%). Omicron, Delta, and Gamma variants were identified in 13 (59%), 8 (36%), and 1 (5%) patients, respectively. In kidney transplant recipients infected with the Omicron variant, the median viral loads at day 0 and day 7 were 752,789 copies/mL (range, 4,000-12,859,300 copies/mL) and 1,353 copies/mL (range, 0-1,211,163 copies/mL), respectively. 2 kidney transplant recipients required hospitalization immediately after sotrovimab perfusion for oxygen therapy that was weaned in 3 days, allowing patients' discharge. None were admitted to the intensive care unit or died. Limitations: Small sample size, no control group. Conclusions: Neutralizing monoclonal antibody therapy is associated with positive outcomes in kidney transplant recipients with mild coronavirus disease 2019, including those infected with the Omicron variant.
RESUMEN
Kidney transplant recipients (KTRs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have an increased risk of mortality compared with the general population and hemodialysis patients. As these patients are immunosuppressed, it might seem obvious to attribute this excess mortality to the impaired immunity induced by immunosuppression. In line with this reasoning is the low immune response, both cellular and humoral, that KTRs mount in response to the anti-SARS-CoV-2 vaccine; however, acute respiratory distress syndrome associated with coronavirus disease 2019 is triggered by a state of inflammation and cytokine release syndrome that lead to pulmonary damage and increased mortality. In that context, immunosuppressive treatment dampening the immune response could, in theory, be potentially beneficial. This review aims at analyzing the current knowledge on the impact of immunosuppressive treatment on mortality in SARS-CoV-2-infected KTRs, the optimal management of immunosuppression in the coronavirus disease 2019 era, and the vaccine response and management in immunosuppressed KTRs.
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Anticuerpos Monoclonales/uso terapéutico , COVID-19 , Trasplante de Riñón , Bélgica , COVID-19/terapia , HumanosAsunto(s)
Anticuerpos Antivirales/sangre , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Inmunogenicidad Vacunal , Trasplante de Riñón/efectos adversos , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Linfocitos T/efectos de los fármacos , Vacunación , Adulto , Anciano , Vacuna BNT162 , Bélgica , COVID-19/inmunología , COVID-19/virología , Femenino , Humanos , Inmunidad Humoral/efectos de los fármacos , Esquemas de Inmunización , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Interferón gamma/metabolismo , Activación de Linfocitos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2/patogenicidad , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/virología , Factores de TiempoAsunto(s)
COVID-19 , Trasplante de Riñón , Vacunas , Anticuerpos Antivirales , Bélgica , Humanos , Trasplante de Riñón/efectos adversos , SARS-CoV-2Asunto(s)
Anticuerpos Antivirales/sangre , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Inmunogenicidad Vacunal , Trasplante de Riñón/efectos adversos , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Vacuna BNT162 , COVID-19/inmunología , COVID-19/virología , Femenino , Humanos , Esquemas de Inmunización , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , SARS-CoV-2/patogenicidad , Factores de Tiempo , Adulto JovenAsunto(s)
COVID-19/etiología , Trasplante de Riñón , Complicaciones Posoperatorias , Adulto , Anciano , Anciano de 80 o más Años , Bélgica/epidemiología , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/terapia , Prueba de COVID-19 , Terapia Combinada , Costo de Enfermedad , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/terapiaRESUMEN
RATIONALE & OBJECTIVE: The world is facing a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although kidney transplant recipients are at increased risk for viral infections, the impact of their chronic immunosuppressed status on the risk for acquiring coronavirus disease 2019 (COVID-19) and disease severity is unknown. STUDY DESIGN: All cases of COVID-19 infection in our cohort of kidney transplant recipients were prospectively monitored. Clinical features, management, and outcomes were recorded. A standard strategy of immunosuppression minimization was applied: discontinue the antimetabolite drug and reduce trough levels of calcineurin or mammalian target of rapamycin inhibitors. Unless contraindicated, hydroxychloroquine was administered only to hospitalized patients. SETTING & PARTICIPANTS: 22 COVID-19 infections were diagnosed in our cohort of 1,200 kidney transplant recipients. RESULTS: Most common initial symptoms included fever, cough, or dyspnea. 18 (82%) patients required hospitalization. Of those patients, 3 had everolimus-based immunosuppression. Computed tomography of the chest at admission (performed in 15 patients) showed mild (n = 3), moderate (n = 8), extensive (n = 1), severe (n = 2), and critical (n = 1) involvement. Immunosuppression reduction was initiated in all patients. Hydroxychloroquine was administered to 15 patients. 11 patients required supplemental oxygen; 2 of them were admitted to an intensive care unit (ICU) with mechanical ventilation. After a median of 10 days, 13 kidney transplant recipients were discharged, 2 were hospitalized in non-ICU units, 1 was in the ICU, and 2 patients had died. LIMITATIONS: Small sample size and short follow-up. CONCLUSIONS: The clinical presentation of COVID-19 infection was similar to that reported in the general population. A standard strategy of immunosuppression minimization and treatment was applied, with 11% mortality among kidney transplant recipients hospitalized with COVID-19 infection.