Position statement of the Spanish Society of Nephrology on the SARS-CoV-2 vaccines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide over the last year causing more than one million deaths. Several treatments have tried to modify the natural history of the coronavirus disease 2019 (COVID-19) but only corticosteroids have demonstrated to be effective in moderate or severe affectation. In that situation, the development of vaccines for preventing the SARS-CoV-2 infection has focused the attention of the scientific community. At present, available messenger RNA-based technology vaccines have received the approval of local and international sanitary authorities. In this position statement, the Spanish Society of Nephrology wants to state that patients with chronic kidney disease and healthcare workers are at high-risk for contagion and complications of COVID-19 so they must have priority in the vaccine administration.

Evolving spectrum but persistent high mortality of COVID-19 among patients on kidney replacement therapy in the vaccine era: the Spanish COVID-19 KRT Registry.

Background: Kidney replacement therapy (KRT) conferred a high risk for coronavirus disease 2019 (COVID-19) related mortality early in the pandemic. We evaluate the presentation, treatment and outcomes of COVID-19 in patients on KRT over time during the pandemic. Methods: This registry-based study involved 6080 dialysis and kidney transplant (KT) patients with COVID-19, representing roughly 10% of total Spanish KRT patients. Epidemiology, comorbidity, infection, vaccine status and treatment data were recorded, and predictors of hospital admission, intensive care unit (ICU) admission and mortality were evaluated. Results: Vaccine introduction decreased the number of COVID-19 cases from 1747 to 280 per wave. Of 3856 (64%) COVID-19 KRT patients admitted to the hospital, 1481/3856 (38%) were admitted during the first of six waves. Independent predictors for admission included KT and the first wave. During follow-up, 1207 patients (21%) died, 500/1207 (41%) during the first wave. Among vaccinated patients, mortality was 19%, mostly affecting KT recipients. Overall, independent predictors for mortality were older age, disease severity (lymphopaenia, pneumonia) and ICU rejection. Among patient factors, older age, male sex, diabetes, KT and no angiotensin receptor blockers (ARB) were independent predictors of death. In KT recipients, individual immunosuppressants were independent predictors of death. Over time, patient characteristics evolved and in later pandemic waves, COVID-19 was mainly diagnosed in vaccinated KT recipients; in the few unvaccinated dialysis patients, ICU admissions increased and mortality decreased (28% for the first wave and 16-22% thereafter). Conclusions: The clinical presentation and outcomes of COVID-19 during the first wave no longer represent COVID-19 in KRT patients, as the pandemic has become centred around vaccinated KT recipients. Vaccines lowered the incidence of diagnosed COVID-19 and mortality. However, mortality remains high despite increased access to ICU care.

Evolving spectrum but persistent high mortality of COVID-19 among patients on kidney replacement therapy in the vaccine era: the Spanish COVID-19 KRT Registry

Background Kidney replacement therapy (KRT) conferred a high risk for COVID-19-related mortality early in the pandemic. We evaluated the presentation, treatment, and outcomes of COVID-19 in patients on KRT over time during the pandemic. Methods This registry-based study involved 6080 dialysis and kidney transplant (KT) patients with COVID-19, representing roughly 10% of total Spanish KRT patients. Epidemiology, comorbidity, infection, vaccine status and treatment data were recorded and predictors of hospital admission, intensive care unit (ICU) admission and mortality evaluated. Results Vaccine introduction decreased COVID-19 cases from 1747 to 280 per wave. Of 3856 (64%) COVID-19 KRT patients admitted to hospital, 1481/3856 (38%) were admitted during the first of six waves. Independent predictors for admission included KT and first wave. During follow-up, 1207 patients (21%) died, 500/1207 (41%) during the first wave. Among vaccinated patients, mortality was 19%, mostly affecting KT recipients. Overall, independent predictors for mortality were older age, disease severity (lymphopenia, pneumonia) and ICU rejection. Among patient factors, older age, male sex, diabetes, KT, and no angiotensin receptor blockers were independent predictors of death. In KT recipients, individual immunosuppressants were independent predictors of death. Over time, patient characteristics evolved and in later pandemic waves, COVID-19 was mainly diagnosed in vaccinated KT recipients and in the few unvaccinated dialysis patients, ICU admissions increased, and mortality decreased (28% for the first wave and 16-22% thereafter). Conclusions The clinical presentation and outcomes of COVID-19 during the first wave no longer represent COVID-19 in KRT patients, as the pandemic has become centred around vaccinated KT recipients. Vaccines lowered the incidence of diagnosed COVID-19 and mortality. However, mortality remains high despite increased access to ICU care. 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.

Management of Hemodialysis Patients with Suspected or Confirmed COVID-19 Infection: Perspective from the Spanish Nephrology.

Background: The recent SARS-CoV-2 coronavirus pandemic has signified a significant effect on the health of the population worldwide. Patients on chronic RRT have been affected by the virus, and they are at higher risk due to the frequent comorbid conditions. Here, we show the results of the COVID-19 Registry of the Spanish Society of Nephrology during the first 6 weeks of the outbreak. Methods: This study is an analysis of the data recorded on a registry of patients with ESKD on RRT who tested positive for COVID-19. The aim was to evaluate clinical conditions, therapeutic management, and consequences, including outcome. The registry began on March 18th, 2020. It includes epidemiologic data, cause of CKD, signs and symptoms of the infection, treatments, and outcomes. Patients were diagnosed with SARS-CoV-2 infection on the basis of the results of PCR of the virus obtained from nasopharyngeal/oropharyngeal swabs. The tests were performed on symptomatic patients and on those who mentioned contact with infected patients. Results: As of May 2, the registry included data on 1397 patients (in-center hemodialysis [IC-HD], 63%; kidney transplant [Tx], 34%; peritoneal dialysis [PD], 3%; and home hemodialysis, 0.3%). The mean age was 67±15 years, and two-thirds were men. Dialysis vintage was 46±41 months, and the time after transplantation was 59±54 months. Eighty-five percent of the patients required hospital admission, and 8% had to be transferred to intensive care units. Overall mortality was 25% (IC-HD, 27%; Tx, 23%; and PD, 15%), and significant proportions of deceased patients have advanced age, are on IC-HD, and presented pneumonia. Age and pneumonia were independently associated with the risk of death. Conclusions: SARS-CoV-2 infection affected a significant number of Spanish patients on RRT, mainly those on IC-HD. Hospitalization rates and mortality were high. The factors more closely related to mortality were age and pneumonia.

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.

Suboptimal personal protective equipment and SARS-CoV-2 infection in Nephrologists: a Spanish national survey.

BACKGROUND: Healthcare workers have been overexposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the current pandemic, but there is little information on the impact of SARS-CoV-2 on nephrologists. The aim of this study was to assess SARS-CoV-2 infections in nephrologists in the first and second pandemic waves, describing risk factors and clinical features. METHODS: This national survey was sent to Spanish nephrologists. Epidemiological data, comorbidities and medications were collected and compared between infected and non-infected nephrologists. Symptoms, prescribed treatments and outcomes are described for infected nephrologists. RESULTS: Three hundred and twenty-seven nephrologists (66% female, age 46 ± 11 years) completed the survey. Of them, 62 (19%) were infected by SARS-CoV-2. Infection was detected by real-time reverse transcription-polymerase chain reaction in the 37 symptomatic patients (62%) and by serological tests in 25 (38%) asymptomatic individuals. Five (8%) of the infected nephrologists were hospitalized. Contrary to the general population, most infections occurred during the first pandemic wave and, specifically, during the first month, when personal protective equipment (PPE) shortages were more severe. Factors associated with infection in univariate analysis were younger age (P = 0.004), work in non-nephrology departments (P = 0.045), higher exposure to coronavirus disease 2019 patients (P < 0.001), lack of appropriate PPE (P < 0.001) and non-O ABO blood group. In an adjusted multivariate model, only lack of appropriate PPE remained predictive of infection [hazard ratio 3.5 (95% confidence interval 1.9-6.8), P < 0.0001]. CONCLUSIONS: SARS-CoV-2 infection was frequent among nephrologists, was frequently diagnosed late and was associated with working conditions.

Predictors of severe COVID-19 in kidney transplant recipients in the different epidemic waves: Analysis of the Spanish Registry.

SARS-CoV-2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID-19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID-19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti-COVID-19 treatment in the second wave (July-December) than in the first one (March-June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post-KT should be considered when selecting recipients for transplantation in the COVID-19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.

Posicionamiento de la Sociedad Española de Nefrología ante a la vacunación frente al SARS-CoV2

Resumen La expansión de la pandemia por el coronavirus de tipo 2 causante del síndrome respiratorio agudo severo (SARS-CoV-2) ha ocasionado más de un millón de muertos en todo el planeta. Un año después de su irrupción, numerosos tratamientos se han postulado sin llegar a alcanzarse resultados clínicamente significativos, a excepción de los corticoides en pacientes con afectación moderada-severa de la enfermedad por coronavirus 19 (COVID-19). En este escenario, la prevención mediante vacunas ha centrado la atención de la comunidad científica. En el momento actual, disponemos de las primeras aprobaciones para el uso de vacunas basadas en ARN mensajero y las agencias locales e internacionales se disponen de manera inminente a su aprobación. Dado que la infección por COVID-19 es frecuente en los pacientes con enfermedad renal terminal y condiciona una elevada mortalidad, desde la Sociedad Española de Nefrología consideramos que los pacientes con enfermedad renal y los profesionales que los atienden deben considerarse prioritarios para recibir la vacuna por su elevado riesgo de contagio y morbi-mortalidad. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide over the last year causing more than one million deaths. Several treatments have tried to modify the natural history of the coronavirus disease 2019 (COVID-19) but only corticosteroids have demonstrated to be effective in moderate or severe affectation. In that situation, the development of vaccines for preventing the SARS-CoV-2 infection has focused the attention of the scientific community. At present, available messenger RNA-based technology vaccines have received the approval of local and international sanitary authorities. In this position statement, the Spanish Society of Nephrology wants to state that patients with chronic kidney disease and healthcare workers are at high-risk for contagion and complications of COVID-19 so they must have priority in the vaccine administration.

Respiratory and Gastrointestinal COVID-19 Phenotypes in Kidney Transplant Recipients.

BACKGROUND: Coronavirus infectious disease 2019 (COVID-19) pandemic has posed at risk the kidney transplant (KT) population. We describe clinical pictures, risk factors for death, and chances to recovery in a large cohort of KT recipients with COVID-19. METHODS: Inclusion in a Spanish prospectively filled registry was allowed for KT cases with confirmed COVID-19. Outcomes were assessed as in-hospital mortality or recovery. RESULTS: The study population comprised of 414 patients. Fever, respiratory symptoms, and dyspnea were the most frequent COVID-19-related symptoms, and 81.4% of them had pneumonia. More than one-third of patients showed digestive symptoms at diagnosis, combinations of nausea, vomiting, and diarrhea. Most patients were hospitalized, 12.1% in intensive care units, and 17.6% needed ventilator support. Treatment for COVID-19 included frequently hydroxychloroquine, azithromycin, high-dose steroids, lopinavir/ritonavir, and tocilizumab. After a mean follow-up of 44 days, the fatality rate was 26.3%. Pneumonia without gastrointestinal symptoms was associated with a 36.3% mortality (respiratory phenotype), and gastrointestinal symptoms without pneumonia with a 5.3% mortality (gastrointestinal phenotype). The mixed pneumonia and gastrointestinal phenotype showed an intermediate mortality of 19.5% (mixed phenotype). Multivariate Cox regression analysis showed that age and pneumonia were independently associated with death, whereas the gastrointestinal phenotype was associated with recovery. CONCLUSIONS: COVID-19 is frequent among the KT population. Advanced age and pneumonia are the main clinical features associated with a high-mortality rate. Gastrointestinal disease is associated with a more benign course and lower mortality.

Use of tocilizumab in kidney transplant recipients with COVID-19.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.