The Obese Taste Bud study: Objectives and study design.

AIMS: Taste modifies eating behaviour, impacting body weight and potentially obesity development. The Obese Taste Bud (OTB) Study is a prospective cohort study launched in 2020 at the University of Leipzig Obesity Centre in cooperation with the HI-MAG Institute. OTB will test the hypothesis that taste cell homeostasis and taste perception are linked to obesity. Here, we provide the study design, data collection process and baseline characteristics. MATERIALS AND METHODS: Participants presenting overweight, obesity or normal weight undergo taste and smell tests, anthropometric, and taste bud density (TBD) assessment on Day 1. Information on physical and mental health, eating behaviour, physical activity, and dental hygiene are obtained, while biomaterial (saliva, tongue swap, blood) is collected in the fasted state. Further blood samples are taken during a glucose tolerance test. A stool sample is collected at home prior to Day 2, on which a taste bud biopsy follows dental examination. A subsample undergoes functional magnetic resonance imaging while exposed to eating-related cognitive tasks. Follow-up investigations after conventional weight loss interventions and bariatric surgery will be included. RESULTS: Initial results show that glycated haemoglobin levels and age are negatively associated with TBD, while an unfavourable metabolic profile, current dieting, and vegan diet are related to taste perception. Olfactory function negatively correlates with age and high-density lipoprotein cholesterol. CONCLUSION: Initial findings suggest that metabolic alterations are relevant for taste and smell function and TBD. By combining omics data from collected biomaterial with physiological, metabolic and psychological data related to taste perception and eating behaviour, the OTB study aims to strengthen our understanding of taste perception in obesity.

State-of-the-Art Opinion Article on Ventilator-Induced Diaphragm Dysfunction: Update on Diagnosis, Clinical Course, and Future Treatment Options.

Evidence from both animal and human studies now supports the development of ventilator-induced diaphragm dysfunction (VIDD) starting as early as 24 h after initiation of mechanical ventilation in the intensive care unit (ICU). However, although the concept of VIDD is now widely accepted, there remain several unanswered questions regarding its pathophysiology, rate of development, and (potentially) recovery after mechanical ventilation.This state-of-the-art opinion article briefly explains VIDD and provides an update on its clinical and prognostic relevance. It then focusses on state-of-the-art diagnostic approaches to determine diaphragm function, strength, and control (neural and peripheral), highlights knowledge gaps relevant to VIDD, and discusses the use of diaphragm pacing for VIDD prevention. It is suggested that future research projects in mechanically ventilated patients would ideally use both cortical and cervical phrenic nerve stimulation studies over time (including also diaphragm electromyography) as the gold standard techniques. This approach has not yet been utilized in a longitudinally designed study in the ICU. Application of these gold standard techniques would allow better understanding of the true pathophysiology and rate of development of VIDD. Notably, these techniques would be superior to diaphragm ultrasound, which yields surrogate markers of diaphragm function only without any direct measure of diaphragm strength or control. It is also suggested that such translational research would further advance understanding of diaphragm pacing as a very promising treatment option for VIDD.

Diaphragm dysfunction as a potential determinant of dyspnea on exertion in patients 1 year after COVID-19-related ARDS.

Some COVID-19 patients experience dyspnea without objective impairment of pulmonary or cardiac function. This study determined diaphragm function and its central voluntary activation as a potential correlate with exertional dyspnea after COVID-19 acute respiratory distress syndrome (ARDS) in ten patients and matched controls. One year post discharge, both pulmonary function tests and echocardiography were normal. However, six patients with persisting dyspnea on exertion showed impaired volitional diaphragm function and control based on ultrasound, magnetic stimulation and balloon catheter-based recordings. Diaphragm dysfunction with impaired voluntary activation can be present 1 year after severe COVID-19 ARDS and may relate to exertional dyspnea.This prospective case-control study was registered under the trial registration number NCT04854863 April, 22 2021.

Key summary of German national treatment guidance for hospitalized COVID-19 patients : Key pharmacologic recommendations from a national German living guideline using an Evidence to Decision Framework (last updated 17.05.2021).

PURPOSE: This executive summary of a national living guideline aims to provide rapid evidence based recommendations on the role of drug interventions in the treatment of hospitalized patients with COVID-19. METHODS: The guideline makes use of a systematic assessment and decision process using an evidence to decision framework (GRADE) as recommended standard WHO (2021). Recommendations are consented by an interdisciplinary panel. Evidence analysis and interpretation is supported by the CEOsys project providing extensive literature searches and living (meta-) analyses. For this executive summary, selected key recommendations on drug therapy are presented including the quality of the evidence and rationale for the level of recommendation. RESULTS: The guideline contains 11 key recommendations for COVID-19 drug therapy, eight of which are based on systematic review and/or meta-analysis, while three recommendations represent consensus expert opinion. Based on current evidence, the panel makes strong recommendations for corticosteroids (WHO scale 5-9) and prophylactic anticoagulation (all hospitalized patients with COVID-19) as standard of care. Intensified anticoagulation may be considered for patients with additional risk factors for venous thromboembolisms (VTE) and a low bleeding risk. The IL-6 antagonist tocilizumab may be added in case of high supplemental oxygen requirement and progressive disease (WHO scale 5-6). Treatment with nMABs may be considered for selected inpatients with an early SARS-CoV-2 infection that are not hospitalized for COVID-19. Convalescent plasma, azithromycin, ivermectin or vitamin D3 should not be used in COVID-19 routine care. CONCLUSION: For COVID-19 drug therapy, there are several options that are sufficiently supported by evidence. The living guidance will be updated as new evidence emerges.

Extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock - Design and rationale of the ECLS-SHOCK trial.

BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted. STUDY DESIGN: The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke. CONCLUSIONS: The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.

Broncho-alveolar lavage in patients with acute respiratory distress syndrome due to COVID-19.

As data about microbiological testing and the cellular composition of the broncho-alveolar lavage (BAL) fluid in patients ventilated due to coronavirus disease 2019 (COVID-19) are lacking, this was investigated in a retrospective analysis (n = 58). Co-infection with pathogens was detected in 31 patients, whereas the analysis of BAL cellularity showed an increased total cell count and an alveolitis dominated by neutrophils. None of the physicians performing bronchoscopies in COVID-19 patients had serological evidence of severe acute respiratory syndrome coronavirus 2 infection.

Thromboembolic and Bleeding Events in COVID-19 Patients receiving Extracorporeal Membrane Oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a potential treatment option in critically ill COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) if mechanical ventilation (MV) is insufficient; however, thromboembolic and bleeding events (TEBE) during ECMO treatment still need to be investigated. METHODS: We conducted a retrospective, single-center study including COVID-19 patients treated with ECMO. Additionally, we performed a univariate analysis of 85 pre-ECMO variables to identify factors influencing incidences of thromboembolic events (TEE) and bleeding events (BE), respectively. RESULTS: Seventeen patients were included; the median age was 57 years (interquartile range [IQR]: 51.5-62), 11 patients were males (65%), median ECMO duration was 16 days (IQR: 10.5-22), and the overall survival was 53%. Twelve patients (71%) developed TEBE. We observed 7 patients (41%) who developed TEE and 10 patients (59%) with BE. Upper respiratory tract (URT) bleeding was the most frequent BE with eight cases (47%). Regarding TEE, pulmonary artery embolism (PAE) had the highest incidence with five cases (29%). The comparison of diverse pre-ECMO variables between patients with and without TEBE detected one statistically significant value. The platelet count was significantly lower in the BE group (n = 10) than in the non-BE group (n = 7) with 209 (IQR: 145-238) versus 452 G/L (IQR: 240-560), with p = 0.007. CONCLUSION: This study describes the incidences of TEE and BE in critically ill COVID-19 patients treated with ECMO. The most common adverse event during ECMO support was bleeding, which occurred at a comparable rate to non-COVID-19 patients treated with ECMO.

Hemodynamic support with Impella ventricular assist device in patients undergoing TAVI: A single center experience.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become a well-established therapeutic option for patients with severe aortic stenosis (AS) at high to intermediate surgical risk. Although TAVI is associated with low mortality of 1.2-6.5%, cardiogenic shock (CS) as a peri-interventional complication remains a challenging problem with very high morbidity and mortality. AIM: This study evaluated the clinical outcome of the use of Impella ventricular assist device in patients undergoing TAVI. METHODS: Between 11/2015 and 08/2018, all patients undergoing TAVI requiring temporary circulatory during the same index hospitalization were included. Primary endpoint was 30-day all-cause mortality. Secondary endpoints were peri-interventional mortality and 30-day stroke rate. RESULTS: Of the 390 patients undergoing TAVI, 13 (3%) required hemodynamic support with an Impella device. Of these, 3 (23%) underwent protected high-risk PCI before TAVI and 10 patients (77%) needed emergency periprocedural hemodynamic support due to cardiogenic shock. Mortality at 30 days was 0% in Impella-protected PCI and 40% with Impella use for periprocedural CS. No stroke occurred in the cohort up to 30 days. Insertion of the Impella device in the setting of TAVI was fast with a mean insertion time of 10 min. Eight patients (80%) in the periprocedural CS group required cardiopulmonary resuscitation prior to Impella use. There was only one device-related complication. CONCLUSIONS: Temporary hemodynamic support with the Impella device in patients with severe aortic valve stenosis or in CS secondary to complicated TAVI was technically doable and allowed stabilization and treatment of salvageable patients.

Outcome predictors of patients with out of hospital cardiac arrest and immediate coronary angiography.

BACKGROUND: Out of hospital cardiac arrest (OHCA) is common and associated with low survival rates. Guidelines propose a fast work-up after OHCA including coronary angiography (CA) but little is known about the actual outcome of those patients who undergo immediate CA after OHCA with suspected cardiac origin. AIM: The aim of this retrospective single-center study was to evaluate the short-term outcomes and predictors of in-hospital mortality in patients who underwent immediate CA after OHCA with suspected cardiac origin. METHODS: We included all consecutive patients with OHCA who underwent immediate CA between January 2011 and December 2015. We defined immediate CA after OHCA as angiography within 2 hr after admission. RESULTS: Two hundred and nineteen consecutive patients with OHCA were included. Fifty six patients (26%) underwent CA without previous return of spontaneous circulation (ROSC) and with ongoing CPR using the LUCAS-device. One hundred and forty nine patients (67%) died in hospital. Of the 56 patients with CA with ongoing CPR, 55 died and only 1 patient survived to hospital discharge. In a multivariate analysis, older age (OR = 2.03, 95%CI 1.35-3.03; p = .001), initial shockable rhythm (OR = 0.28, 95%CI 0.07-1.13; p = .076), CA with ongoing CPR (OR = 11.63, 95%CI 1.20-122.55; p = .035), and initial arterial pH (OR = 0.008, 95%CI 0.00-0.228; p < .005) remained as independent predictors for in-hospital mortality. CONCLUSIONS: In this study older age, metabolic derangement on admission, initial nonshockable rhythm and failure to achieve ROSC before admission predicted in-hospital mortality. While CA with ongoing CPR with the LUCAS-device was feasible, mortality in patients without previous ROSC was extremely high, questioning whether this approach is medically useful.

Ethics rounds: affecting ethics quality at all organisational levels.

Clinical ethics support (CES) services are experiencing a phase of flourishing and of growing recognition. At the same time, however, the expectations regarding the acceptance and the integration of traditional CES services into clinical processes are not met. Ethics rounds as an additional instrument or as an alternative to traditional clinical ethics support strategies might have the potential to address both deficits. By implementing ethics rounds, we were able to better address the needs of the clinical sections and to develop a more comprehensive account of ethics quality in our hospital, which covers the level of decisions and actions, and also the level of systems and processes and aspects of ethical leadership.

De Ritis Ratio to Predict Clinical Outcomes of Intermediate- and High-Risk Pulmonary Embolisms.

Background: Abnormal liver function tests can identify severe cardiopulmonary failure. The aspartate transaminase/alanine transaminase (AST/ALT) ratio, or the De Ritis ratio, is commonly used to evaluate acute liver damage. However, its prognostic value in pulmonary embolism (PE) is unknown. Methods: Two cohorts, including patients with intermediate- and high-risk PEs, were established: one with an abnormal baseline AST/ALT ratio (>1) and another with a normal baseline AST/ALT ratio (<1). The primary outcome was a 60-day mortality. Secondary outcomes included peak N-terminal pro-brain-natriuretic-peptide (NT-proBNP) levels, complications, and the need for critical care treatment. To assess the effect of abnormal AST/ALT ratios, inverse probability weighted (IPW) analyses were performed. Results: In total, 230 patients were included in the analysis, and 52 (23%) had an abnormal AST/ALT ratio. After the IPW correction, patients with an abnormal AST/ALT ratio had a significantly higher mortality rate and peak NT-proBNP levels. The relative risks of 60-day mortality, shock development, use of inotropes/vasopressors, mechanical ventilation, and extracorporeal life support were 9.2 (95% confidence interval: 3.3-25.3), 10.1 (4.3-24), 2.7 (1.4-5.2), 2.3 (1.4-3.7), and 5.7 (1.4-23.1), respectively. Conclusions: The baseline AST/ALT ratio can be a predictor of shock, multiorgan failure, and mortality in patients with a pulmonary embolism.

First Ultrasound-Assisted Thrombolysis for Pulmonary Embolism after Lung Surgery.

Background Experience with early postoperative catheter-directed ultrasound-assisted thrombolysis (USAT) in high-risk pulmonary embolism (PE) is limited. A first case of USAT directly after pulmonary surgery is presented. Case Description A 60-year-old female patient with two malignancies (triple negative breast cancer and pulmonary squamous cell carcinoma) underwent video-assisted lobectomy. The second postoperative day, she developed PE with hemodynamic deterioration. Note that 24 mg of alteplase was applied by USAT. After 3 days she was successfully weaned from ventilation and vasopressors. Conclusion USAT for acute PE is possible after major pulmonary resections and seems promising if reperfusion is needed.

In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation. METHODS: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic-from March 1 to Sept 13, 2020-at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing. FINDINGS: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46-60]) were included in the study. Median ECMO duration was 15 days (IQR 8-27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms. INTERPRETATION: Patient's age, timing of cannulation (<4 days vs ≥4 days from intubation), and use of inotropes and vasopressors are essential factors to consider when analysing the outcomes of patients receiving ECMO for COVID-19. Despite post-discharge survival being favourable, persisting long-term symptoms suggest that dedicated post-ECMO follow-up programmes are required. FUNDING: None.

The Potential Impact of Heparanase Activity and Endothelial Damage in COVID-19 Disease.

SARS-CoV-2 was first detected in 2019 in Wuhan, China. It has been found to be the most pathogenic virus among coronaviruses and is associated with endothelial damage resulting in respiratory failure. Determine whether heparanase and heparan sulfate fragments, biomarkers of endothelial function, can assist in the risk stratification and clinical management of critically ill COVID-19 patients admitted to the intensive care unit. We investigated 53 critically ill patients with severe COVID-19 admitted between March and April 2020 to the University Hospital RWTH Aachen. Heparanase activity and serum levels of both heparanase and heparan sulfate were measured on day one (day of diagnosis) and day three in patients with COVID-19. The patients were classified into four groups according to the severity of ARDS. When compared to baseline data (day one), heparanase activity increased and the heparan sulfate serum levels decreased with increasing severity of ARDS. The heparanase activity significantly correlated with the lactate concentration on day one (r = 0.34, p = 0.024) and on day three (r = 0.43, p = 0.006). Heparanase activity and heparan sulfate levels correlate with COVID-19 disease severity and outcome. Both biomarkers might be helpful in predicting clinical course and outcomes in COVID-19 patients.

Extracorporeal membrane oxygenation in patients with COVID-19: 1-year experience.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) in patients with coronavirus disease 2019 (COVID-19) showed reasonable outcomes. However, recent studies indicated a negative trend and analysis is needed. METHODS: Baseline characteristics, laboratory parameters, and outcomes of ECMO-supported patients with COVID-19 were analyzed in a retrospective single-center study. We included hospital admissions until February 28, 2021; patients were followed until discharge/death. Eventually, we compared data between patients hospitalized before and after September 1, 2020. RESULTS: Median age of patients treated with ECMO (n=39) was 56 years; most patients were males (n=28, 72%). Median mechanical ventilation time (prior to ECMO) was 6 days, while the median ECMO duration was 19 days. Overall survival rate was 41%. In the sub-analysis, survival until discharge in the first and second epidemic waves was 53% (n=19) and 30% (n=20), respectively (P=0.2). At baseline, compared with patients of the first wave, those of the second wave had higher median body mass index (28.2 vs. 31.1 kg/m2, respectively, P=0.02), bicarbonate (27 vs. 31.8 mmol/L, respectively, P=0.033), plasma free hemoglobin (36 vs. 58 mg/L, respectively, P=0.013), alanine aminotransferase (33 vs. 52 U/L, respectively, P=0.018), and pH (7.29 vs. 7.42, respectively, P=0.005), lower rate of pulmonary hypertension (32% vs. 0%, respectively, P=0.008), lower positive end-expiratory pressure (14 vs. 12 cmH2O, respectively, P=0.04), longer median ECMO duration (16 vs. 24.5 days, respectively, P=0.074), and more frequent major bleeding events (42% vs. 80%, respectively, P=0.022). CONCLUSIONS: ECMO-supported patients with COVID-19 had an overall survival rate of 41%. Similar to international registries, we observed less favorable outcomes during the second wave. Further research is needed to confirm this signal and find predictors for mortality.

Six Months Follow-Up of Patients with Invasive Mechanical Ventilation due to COVID-19 Related ARDS.

Although patients who recovered from acute coronavirus disease 2019 (COVID-19) may have prolonged disabilities, follow-up data of those who have survived COVID-19 related acute respiratory distress syndrome (ARDS) is still very scarce. Therefore, COVID-19-ARDS survivors requiring invasive mechanical ventilation (IMV) were followed six months after discharge. Pulmonary function tests (PFTs), 6-min walk test (6MWT) and echocardiography were performed. Quality of life (QoL), depression and anxiety were assessed using validated questionnaires. Patients were compared based on respiratory mechanics and CT-phenotype during intensive care unit (ICU) stay. Eighteen patients were included (61 ± 7 years; ICU-stay: 34 ± 16 days; IMV: 30 ± 15 days). At follow-up (197 ± 15 days after discharge), PFTs did not reveal significant limitations (VC: 92 ± 16%; FEV1: 92 ± 20%; DLco/VA: 81 ± 16%). Cardiac systolic function was normal in all patients, but 50% of them had diastolic dysfunction. 6MWT was under the lower limit of normal in only two patients. Eight patients (44%) reported tiredness, six (33%) suffered from fatigue and one patient (6%) had depression and anxiety. Surprisingly, patients with worse respiratory mechanics during IMV reported fewer symptoms and less exertional dyspnea at follow-up. In conclusion, patients with COVID-19-ARDS have the possibility to fully recover regarding pulmonary function and exercise capacity, which seems to be independent of disease severity during ICU stay.

Prognostic Value of Bioactive Adrenomedullin in Critically Ill Patients with COVID-19 in Germany: An Observational Cohort Study.

The coronavirus disease 2019 (COVID-19) pandemic has placed a significant burden on hospitals worldwide. Objective biomarkers for early risk stratification and clinical management are still lacking. The aim of this work was to determine whether bioactive adrenomedullin can assist in the risk stratification and clinical management of critically ill COVID-19 patients. Fifty-three patients with confirmed COVID-19 were included in this prospective observational cohort study between March and April 2020. Bioactive adrenomedullin (bio-ADM) plasma concentration was measured daily for seven days after admission. The prognostic value and clinical significance of bio-ADM plasma levels were evaluated for the severity of respiratory failure, the need for extracorporeal organ support and outcome (28-day mortality). Bio-ADM levels increased with the severity of acute respiratory distress syndrome (ARDS; p < 0.001) and were significantly elevated in invasively ventilated patients (p = 0.006) and patients in need of extracorporeal membrane oxygenation (p = 0.040) or renal replacement therapy (RRT; p < 0.001) compared to patients without these conditions. Non-survivors showed significantly higher bio-ADM levels than survivors (p = 0.010). Bio-ADM levels predicted 28-day mortality (C-index 0.72, 95% confidence interval 0.56-0.87, p < 0.001). Bio-ADM plasma levels correlate with disease severity, the need for extracorporeal organ assistance, and outcome, and highlight the promising value of bio-ADM in the early risk stratification and management of patients with COVID-19.

Time on previous renal replacement therapy is associated with worse outcomes of COVID-19 in a regional cohort of kidney transplant and dialysis patients.

ABSTRACT: Chronic renal replacement therapy by either a kidney transplant (KTX) or hemodialysis (HD) predisposes patients to an increased risk for adverse outcomes of COVID-19. However, details on this interaction remain incomplete. To provide further characterization, we undertook a retrospective observational cohort analysis of the majority of the hemodialysis and renal transplant population affected by the first regional outbreak of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) in Germany. In a region of 250,000 inhabitants we identified a total of 21 cases with SARS-CoV-2 among 100 KTX and 260 HD patients, that is, 7 KTX with COVID-19, 14 HD with COVID-19, and 3 HD with asymptomatic carrier status. As a first observation, KTX recipients exhibited trends for a higher mortality (43 vs 18%) and a higher proportion of acute respiratory distress syndrome (ARDS) (57 vs 27%) when compared to their HD counterparts. As a novel finding, development of ARDS was significantly associated with the time spent on previous renal replacement therapy (RRT), defined as the composite of dialysis time and time on the transplant (non-ARDS 4.3 vs ARDS 10.6 years, P = .016). Multivariate logistic regression analysis showed an OR of 1.7 per year of RRT. The association remained robust when analysis was confined to KTX patients (5.1 vs 13.2 years, P = .002) or when correlating the time spent on a renal transplant alone (P = .038). Similarly, longer RRT correlated with death vs survival (P = .0002). In conclusion our data suggest renal replacement vintage as a novel risk factor for COVID-19-associated ARDS and death. The findings should be validated by larger cohorts.

Early risk markers for severe clinical course and fatal outcome in German patients with COVID-19.

BACKGROUND: Some patients with Corona Virus Disease 2019 (COVID-19) develop a severe clinical course with acute respiratory distress syndrome (ARDS) and fatal outcome. Clinical manifestations and biomarkers in early stages of disease with relevant predictive impact for outcomes remain largely unexplored. We aimed to identify parameters which are significantly different between subgroups. DESIGN: 125 patients with COVID-19 were analysed. Patients with ARDS (N = 59) or non-ARDS (N = 66) were compared, as well as fatal outcome versus survival in the two groups. KEY RESULTS: ARDS and non-ARDS patients did not differ with respect to comorbidities or medication on developing a fatal outcome versus survival. Body mass index was higher in patients with ARDS versus non-ARDS (p = 0.01), but not different within the groups in survivors versus non-survivors. Interleukin-6 levels on admission were higher in patients with ARDS compared to non-ARDS as well as in patients with fatal outcome versus survivors, whereas lymphocyte levels were lower in the different subgroups (all p<0.05). There was a highly significant 3.5-fold difference in fever load in non-survivors compared to survivors (p<0.0001). Extrapulmonary viral spread was detected more often in patients with fatal outcome compared to survivors (P = 0.01). Further the detection of SARS-CoV-2 in serum showed a significantly more severe course and an increased risk of death (both p<0.05). CONCLUSIONS: We have identified early risk markers for a severe clinical course, like ARDS or fatal outcome. This data might help develop a strategy to address new therapeutic options early in patients with COVID-19 and at high risk for fatal outcome.