COVID-19 in transplant recipients: The Spanish experience

We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5;95% CI: 1.4-4.6), age >60 years (OR: 3.7;95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0;95% CI: 1.9-4.9).

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

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.

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.

COVID-19 in transplant recipients: The Spanish experience.

We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-ß (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).

Clinical characteristics and risk factors for severe COVID-19 in hospitalized kidney transplant recipients: A multicentric cohort study.

Kidney transplant recipients might be at higher risk for severe coronavirus disease 2019 (COVID-19). However, risk factors for relevant outcomes remain uncertain in this population. This is a multicentric kidney transplant cohort including 104 hospitalized patients between March 4 and April 17, 2020. Risk factors for death and acute respiratory distress syndrome (ARDS) were investigated, and clinical and laboratory data were analyzed. The mean age was 60 years. Forty-seven patients (54.8%) developed ARDS. Obesity was associated to ARDS development (OR 2.63; P = .04). Significant age differences were not found among patients developing and not developing ARDS (61.3 vs 57.8 years, P = .16). Seventy-six (73%) patients were discharged, and 28 (27%) died. Death was more common among the elderly (55 and 70.8 years, P < .001) and those with preexisting pulmonary disease (OR 2.89, P = .009). At admission, higher baseline lactate dehydrogenase (257 vs 358 IU/mL, P = .001) or ARDS conferred higher risk of death (HR 2.09, P = .044). In our cohort, ARDS was equally present among young and old kidney recipients. However, the elderly might be at higher risk of death, along with those showing higher baseline LDH at admission.