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Background: Several observations indicate a hyperinflammatory state in severely ill COVID-19 patients as target for therapeutic interventions. The aim of this study was to investigate the effect of extracorporeal cytokine elimination by CytoSorb on COVID-19 associated vasoplegic shock. Methods: In this prospective randomized pilotstudy patients with vasoplegic shock requiring norepinephrine >0.2 μg/kg/min, CRP >100 mg/L and indication for kidney replacement therapy were randomized 1:1 to receive CytoSorb treatment for 3-7 days or standard of care. The primary endpoint was time until resolution of vasoplegic shock (freedom of vasopressor therapy for at least 8 hours to sustain a MAP ≥65mmHg). Data were analyzed using Cox-regression and Kaplan-Meier curves. Results: From November 2020 -March 2021 50 patients were enrolled. Of these 23 patients received CytoSorb treatment, 26 patients received standard of care and 1 patient had to be excluded due to withdrawal of informed consent. The median age was 61 (IQR 58-65) years in the CytoSorb group and 66 (IQR 60-71) years in the control group. Patients were predominantly male (CytoSorb 91.3% vs. control 76.9%). Comorbidities and indicators for disease severity were well balanced. The primary endpoint was reached in 13/23 patients (56.5%) in the CytoSorb and 12/26 patients (46.2%) in the control group after a median of 5 (IQR 4-5) and 4 days (IQR 3-5), respectively (Figure 1a). The Coxregression analysis for the primary endpoint showed no statistically significant difference between the groups with and without adjustment for the predefined additional variables age, gender, ECMO-therapy or time from beginning of shock until study inclusion. ICUmortality was high with 18/23 (78%) deaths in the CytoSorb and 19/26 (73%) deaths in the control group (Figure 1b). Conclusions: In this pilot trial in severely ill COVID-19 patients CytoSorb treatment did neither lead to a faster resolution of vasoplegic shock as compared to standard of care, nor was it associated with altered mortality.
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Background: Acute kidney injury (AKI) is frequently observed in critically ill patients and is associated with a poor prognosis. AKI has recently moved into the focus of interest during the SARS-CoV-2 pandemic as high rates of AKI have been reported in severe COVID-19. We aimed to delineate cell type-specific molecular phenotypes associated with human AKI, including COVID-associated AKI. Methods: We analyzed human kidney tissues using histology and single-nuclei RNA sequencing. Samples included kidney biopsies obtained within 2 hours post mortem from patients who succumbed to critical illness with and without evidence of AKI. Samples also included tumor-adjacent normal kidney tissues obtained during surgeries. AKI cases included patients with severe courses of COVID-19 (COVID AKI) and patients with other types of critical illness associated with systemic inflammation (Non-COVID AKI). Postmortem kidney tissues obtained 30 min, 1 hour and 2 hours after death from a brain-dead patient without AKI were analyzed to assess the impact of post-mortem effects. Results: Single-nuclei sequencing from kidney tissues yielded data of high transcriptional depth, which allowed transcriptome-based identification and de-novo spatial reconstruction of kidney cells. Principal component and differential gene expression analyses indicated that the presence of clinically confirmed AKI was the primary driver of global kidney transcriptomes and that different molecular subtypes of AKI existed. In contrast, the sampling time post-mortem and the presence of COVID-19 had minor effects. Subclustering analyses of different kidney cell types identified subclasses of cells representing injured kidney tubular cells, which were marked by distinct biomarker expression and expression signatures signifying intrinsic responses to inflammation, an induction of epithelial-to-mesenchymal transition, and an upregulation of hitheto unrecognized novel receptor-ligand pairs. Conclusions: We provide the first cell type-specific molecular atlas of human AKI, revealing unanticipated disease subtypes and cell type-specific injury patterns.
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Introduction: Candida auris is an emerging pathogen in hospital infections that can present multi-resistance to antifungals and causes outbreaks. Objectives: The aim is to describe the infection prevention and control for C. auris. Methods: Identification of yeast isolates was performed by MALDITOF and confirmed by ITS sequencing. Infection control measures were decided by a multi-disciplinary ad hoc outbreak panel. Patient screening once or twice a week and extensive environmental testing for C. auris was conducted. Results: C. auris was isolated from a urine sample of a COVID-19 patient who had been transferred from an Egyptian hospital to our COVID-19 intensive care unit (ICU). Immediately, disinfection routine was changed, because C. auris is insensitive to quaternary ammonium compounds. The patient had already been isolated from admission due to evidence of 4MRGN Klebsiella pneumoniae. Six days after confirmation of C. auris in the index patient, a second COVID-19 patient was identified with C. auris. Both patients were isolated in a separated area of the ICU. Strict hygiene and infection control measures were implemented promptly. In the nine weeks from initial confirmation of C. auris and discharge of the two affected patients, C. auris was repeatedly identified in clinical samples of them. However, it was not detected in any other patient on the ICU (n = 7) or discharged from it (n = 13) nor in any environmental sample (n = 129). The two C. auris patients had been intubated using the same video laryngoscope seven days apart. Although the equipment and the spatulas had been manually reprocessed using chlorine dioxide-soaked wipes they might serve as transmission vehicle. Therefore, it was recommended to use disposable spatulas. Conclusion: A rapid confirmation of a C. auris in the lab and the immediate implementation of adequate hygiene measures at the ward are crucial in order to prevent transmission of C. auris to other patients.