Hepatobiliary long-term consequences of COVID-19: dramatically increased rate of secondary sclerosing cholangitis in critically ill COVID-19 patients.

BACKGROUND: Increasing evidence suggests that secondary sclerosing cholangitis (SSC), which can lead to cirrhosis or liver failure, may be a hepatobiliary long-term complication of COVID-19. The aim of this study was to estimate the frequency and outcome of this COVID-19 sequela and to identify possible risk factors. METHODS: This observational study, conducted at University Hospital Charité Berlin and Unfallkrankenhaus Berlin, Germany, involved hospitalized patients with COVID-19 pneumonia, including 1082 ventilated COVID-19 patients. We compared COVID-19 patients who developed SSC with a COVID-19 control group by univariate and multivariate analyses. RESULTS: SSC occurrence after COVID-19 was observed exclusively in critically ill patients with invasive ventilation, albeit with extreme clustering among them. One in every 43 invasively ventilated COVID-19 patients developed this complication. Risk factors preceding the development of secondary sclerosing cholangitis in critically ill COVID-19 patients (SSC-CIP) were signs of systemic reduced blood oxygen supply (e.g., low PaO2/FiO2, ischemic organ infarctions), multi-organ failure (high SOFA score) at admission, high fibrinogen levels and intravenous ketamine use. Multivariate analysis confirmed fibrinogen and increased plasma lactate dehydrogenase as independent risk factors associated with cholangiopathy onset. The 1-year transplant-free survival rate of COVID-19-associated SSC-CIP was 40%. CONCLUSIONS: COVID-19 causes SSC-CIP in a substantial proportion of critically ill patients. SSC-CIP most likely develops due to severe tissue hypoxia and fibrinogen-associated circulatory disturbances. A significant increase of patients with SSC-CIP is to be expected in the post-COVID era.

Use of Hemoadsorption in Patients With Severe Intoxication Requiring Extracorporeal Cardiopulmonary Support-A Case Series.

Drugs intoxications often lead to severe vasoplegia and cardiogenic shock, and VA-ECMO represents a viable therapy option. However, as cardiopulmonary support is not contributing to the removal of the causal agent from the blood, detoxification by a new hemoadsorption device (CytoSorb) could represent a potential therapeutic tool due to its highly efficient elimination capacity of endogenous but also exogenous hydrophobic substances for which otherwise no effective antidote exist. In this case series, four anecdotal cases of acute intoxications requiring VA-ECMO support used as extracorporeal cardiopulmonary resuscitation after intoxication-induced out-of-hospital cardiac arrest (OHCA) are presented, who were additionally treated with CytoSorb hemoadsorption in combination with renal replacement therapy. Combined treatment was associated with a considerable decrease in plasma levels of the overdosed drugs. Additionally, the combination of applied techniques was safe, practical, and technically feasible with no adverse or any device-related side effects documented during or after the treatment sessions. Based on the reported dramatic decline in drug levels during treatment, that fits in the device's characteristics, we strongly suggest to further investigate the potentially lifesaving role of CytoSorb therapy in patients with acute intoxications requiring multiple organ support techniques.

Critical Illness and Systemic Inflammation Are Key Risk Factors of Severe Acute Kidney Injury in Patients With COVID-19.

INTRODUCTION: Acute kidney injury (AKI) is an important complication in COVID-19, but its precise etiology has not fully been elucidated. Insights into AKI mechanisms may be provided by analyzing the temporal associations of clinical parameters reflecting disease processes and AKI development. METHODS: We performed an observational cohort study of 223 consecutive COVID-19 patients treated at 3 sites of a tertiary care referral center to describe the evolvement of severe AKI (Kidney Disease: Improving Global Outcomes stage 3) and identify conditions promoting its development. Descriptive statistics and explanatory multivariable Cox regression modeling with clinical parameters as time-varying covariates were used to identify risk factors of severe AKI. RESULTS: Severe AKI developed in 70 of 223 patients (31%) with COVID-19, of which 95.7% required kidney replacement therapy. Patients with severe AKI were older, predominantly male, had more comorbidities, and displayed excess mortality. Severe AKI occurred exclusively in intensive care unit patients, and 97.3% of the patients developing severe AKI had respiratory failure. Mechanical ventilation, vasopressor therapy, and inflammatory markers (serum procalcitonin levels and leucocyte count) were independent time-varying risk factors of severe AKI. Increasing inflammatory markers displayed a close temporal association with the development of severe AKI. Sensitivity analysis on risk factors of AKI stage 2 and 3 combined confirmed these findings. CONCLUSION: Severe AKI in COVID-19 was tightly coupled with critical illness and systemic inflammation and was not observed in milder disease courses. These findings suggest that traditional systemic AKI mechanisms rather than kidney-specific processes contribute to severe AKI in COVID-19.