URINARY BIOMARKERS TO PREDICT ACUTE KIDNEY DAMAGE AND MORTALITY IN COVID-19

BACKGROUND AND AIMS: Acute kidney injury (AK) is a frequent condition in patients hospitalized for COVID-19. There are only few reports on the use of urinary biomarkers in COVID-19 and no data comparing the prognostic use of individual biomarkers in the prediction of adverse outcome so far. METHOD: We performed a prospective monocentric study on the value of urinary biomarkers to predict the composite endpoint of a transfer to the intensive care unit (ICU), the need for renal replacement therapy (RRT), mechanical ventilation and in-hospital mortality. A total of 41 patients hospitalized for COVID-19 were enrolled in this study. Urine samples were obtained shortly after admission in order to assess neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), calprotectin and vanin-1. RESULTS: We identified calprotectin as a predictor of a severe course of the disease, requiring intensive care treatment (AUC 0.728, P = .016). Positive and negative predictive values were 78.6% and 76.9%, respectively, using a cut-off concentration of 127.8 ng/mL. NGAL tended to predict COVID-19 associated AKI without reaching statistical significance (AUC 0.669, P = .053). The best parameter in the prediction of in-hospital mortality was NGAL as well (AUC 0.674, P = .077). KIM-1 and vanin-1 did not reach significance for any of the investigated endpoints. CONCLUSION: While KIM-1 and vanin-1 did not provide prognostic clinical information in the context of COVID-19, this study shows that urinary calprotectin and NGAL concentrations are independent predictors of an adverse course of the disease. Calprotectin and NGAL may thereby constitute helpful adjuncts in the identification of patients at increased risk who may benefit from upcoming antiviral agents to SARS-CoV-2.

Psychological responses to the covid-19 pandemic in renal transplant recipients

Introduction: With regard to immunosuppression and the high level of cardiovascular comorbidity renal transplant recipients are supposed to be at substantially increased risk for an adverse course of COVID-19. To date, there are no data on the psychological effects of this knowledge on renal transplant recipients during the pandemic. Methods: Cross sectional study on 62 renal transplant recipients and 30 nephrological outpatients without immunosuppression, who served as control. The study aimed at an assessment of anxiety, mood, and quality of life during the pandemic (April 2020) and six months before. The analysis was performed by means of a questionnaire derived from KPD-38. The KPD-38 encompasses 38 questions on 6 parameters. We extracted 6 questions focussing on two parameters: life satisfaction and competence to act. The corresponding scales ranged from 1 to 4. Statistical analysis was performed using the Wilcoxon Test for the intragroup comparison of the two timepoints and the Mann-Whitney U test for intergroup comparisons. Results: The renal transplant recipients had a mean level of satisfaction of 5.4±1.9 in April 2020 during the pandemic compared to 6.4±1.6 six months ago (p=0.0001). In the control group the life satisfaction was lower during the pandemic than six months ago as well (5.6±1.6 vs. 6.7±2.6, p=0.0073). The level of satisfaction during the pandemic did not significantly differ between transplant recipients and controls (p=0.69). In analogy to the parameter 'life satisfaction', the parameter 'competence to act' was higher before than during the pandemic in both renal transplant recipients(12.7±3.0 vs. 14.7±2.7, p<0.0001) and control subjects (13.3±3.1 vs. 14.7±2.7, p=0.016) and showed no significant difference between the two groups during the pandemic (12.7±3.0 vs. 13.3±3.1, p=0.361). Conclusion: Life satisfaction and the feeling of 'competence to act' were significantly reduced during the COVID-19 pandemic in renal transplant recipients. This phenomenon, however, occurred in the same way in nonimmunocompromised subjects with CKD.

Allograft infiltration and meningoencephalitis by sars-cov-2 in a pancreas-kidney transplant recipient

Introduction: COVID-19 primarily affects epithelia of the upper and lower respiratory tract. Thus, impairment of kidney function has been primarily attributed to secondary effects like cytokine release or fluid balance disturbances so far. Methods: We provide evidence that SARS-CoV-2 can directly infiltrate a kidney allograft. Results: A 69-year old male pancreas-kidney transplant recipient presented to our hospital with COVID-19 pneumonia and impaired pancreas and kidney allograft function. Kidney biopsy was performed showing tubular damage and an interstitial mononuclear cell infiltrate. RT-PCR from the biopsy specimen was positive for SARS-CoV-2, while being negative in a peripheral blood sample. Subsequently, he suffered from two convulsive seizures. Magnetic resonance tomography suggested meningoencephalitis, which was confirmed by SARS-CoV-2 RNA transcripts in the cerebrospinal fluid. Conclusion: The present case demonstrates that SARS-CoV-2 can infiltrate diverse organs. The patient suffered from COVID-19 pneumonia, meningoencephalitis and nephritis. SARS-CoV-2 binds to its target cells through angiotensin-converting enzyme 2, which is expressed in a broad variety of tissues including the lung, brain and kidney. SARS-CoV-2 thereby shares features with other human coronaviruses including SARS-CoV that were identified as pathogens beyond the respiratory tract as well. The present case should provide awareness that extrapulmonary symptoms in COVID-19 may be attributable to viral infiltration of diverse organs.

Transplant patients are able to mount sars-cov-2-reactive t-cell response with the magnitude and functionality comparable to non-immunosuppressed patients

Introduction: The optimal management of COVID-19 in transplant patients is not defined so far. The major concern is the ability of transplant patients to generate a sufficient antiviral response under immunosuppressive treatment. Methods: Here, we analysed T-cell immunity directed against Spike, Membrane and Nucleocapsid proteins of SARS-CoV-2 in a small cohort of 6 transplant patients (TP) with COVID-19 in comparison to 28 non-immunosuppressed patients (NIP). Results: The median patient age of transplant cohort (3 renal transplant, 1 lung, and 1 combined liver-kidney and 1 pancreas-kidney) as well as gender did not differ from NIP. We also did not find statistical differences for the time between the diagnosis of COVID-19 and analysis of T-cell immunity between the two cohorts. Notably, despite immunosuppressive therapy, we were able to detect a strong antiviral response in transplant patients. TP generated SARSCoV-2 reactive T-cells against all three proteins with predominance of CD4 + T cells with pro-inflammatory Th1 phenotype. Moreover, SARS-CoV-2 reactive CD4 + and CD8 + T cells were able to produce multiple pro-inflammatory cytokines demonstrating their potential protective capacity. Of interest, the frequencies and cytokine production patterns of SARS-CoV-2 reactive T-cells did not show any differences between TP and NIP. Conclusion: A strong polyfunctional T-cell response directed against all three SARS-CoV-2 proteins can be generated in transplant despite immunosuppressive treatment. In comparison to non-immunosuppressed patients, the antiviral immunity is non-inferior. Since the dosage of immunosuppression in analysed patients was reduced, further studies are required to assess the antiviral immunity under standard immunosuppression.