Hospitalized patients dying with SARS-CoV-2 infection-An analysis of patient characteristics and management in ICU and general ward of the LEOSS registry.

BACKGROUND: COVID-19 is a severe disease with a high need for intensive care treatment and a high mortality rate in hospitalized patients. The objective of this study was to describe and compare the clinical characteristics and the management of patients dying with SARS-CoV-2 infection in the acute medical and intensive care setting. METHODS: Descriptive analysis of dying patients enrolled in the Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS), a non-interventional cohort study, between March 18 and November 18, 2020. Symptoms, comorbidities and management of patients, including palliative care involvement, were compared between general ward and intensive care unit (ICU) by univariate analysis. RESULTS: 580/4310 (13%) SARS-CoV-2 infected patients died. Among 580 patients 67% were treated on ICU and 33% on a general ward. The spectrum of comorbidities and symptoms was broad with more comorbidities (≥ four comorbidities: 52% versus 25%) and a higher age distribution (>65 years: 98% versus 70%) in patients on the general ward. 69% of patients were in an at least complicated phase at diagnosis of the SARS-CoV-2 infection with a higher proportion of patients in a critical phase or dying the day of diagnosis treated on ICU (36% versus 11%). While most patients admitted to ICU came from home (71%), patients treated on the general ward came likewise from home and nursing home (44% respectively) and were more frequently on palliative care before admission (29% versus 7%). A palliative care team was involved in dying patients in 15%. Personal contacts were limited but more often documented in patients treated on ICU (68% versus 47%). CONCLUSION: Patients dying with SARS-CoV-2 infection suffer from high symptom burden and often deteriorate early with a demand for ICU treatment. Therefor a demand for palliative care expertise with early involvement seems to exist.

All-cause mortality and disease progression in SARS-CoV-2-infected patients with or without antibiotic therapy: an analysis of the LEOSS cohort.

PURPOSE: Reported antibiotic use in coronavirus disease 2019 (COVID-19) is far higher than the actual rate of reported bacterial co- and superinfection. A better understanding of antibiotic therapy in COVID-19 is necessary. METHODS: 6457 SARS-CoV-2-infected cases, documented from March 18, 2020, until February 16, 2021, in the LEOSS cohort were analyzed. As primary endpoint, the correlation between any antibiotic treatment and all-cause mortality/progression to the next more advanced phase of disease was calculated for adult patients in the complicated phase of disease and procalcitonin (PCT) ≤ 0.5 ng/ml. The analysis took the confounders gender, age, and comorbidities into account. RESULTS: Three thousand, six hundred twenty-seven cases matched all inclusion criteria for analyses. For the primary endpoint, antibiotic treatment was not correlated with lower all-cause mortality or progression to the next more advanced (critical) phase (n = 996) (both p > 0.05). For the secondary endpoints, patients in the uncomplicated phase (n = 1195), regardless of PCT level, had no lower all-cause mortality and did not progress less to the next more advanced (complicated) phase when treated with antibiotics (p > 0.05). Patients in the complicated phase with PCT > 0.5 ng/ml and antibiotic treatment (n = 286) had a significantly increased all-cause mortality (p = 0.029) but no significantly different probability of progression to the critical phase (p > 0.05). CONCLUSION: In this cohort, antibiotics in SARS-CoV-2-infected patients were not associated with positive effects on all-cause mortality or disease progression. Additional studies are needed. Advice of local antibiotic stewardship- (ABS-) teams and local educational campaigns should be sought to improve rational antibiotic use in COVID-19 patients.

Gastrointestinal bleeding and endoscopic findings in critically and non-critically ill patients with corona virus disease 2019 (COVID-19): Results from Lean European Open Survey on SARS-CoV-2 (LEOSS) and COKA registries.

BACKGROUND: Corona virus disease 2019 (COVID-19) patients are at increased risk for thromboembolic events. It is unclear whether the risk for gastrointestinal (GI) bleeding is also increased. METHODS: We considered 4128 COVID-19 patients enrolled in the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. The association between occurrence of GI bleeding and comorbidities as well as medication were examined. In addition, 1216 patients from COKA registry were analyzed focusing on endoscopy diagnostic findings. RESULTS: A cumulative number of 97 patients (1.8%) with GI bleeding were identified in the LEOSS registry and COKA registry. Of 4128 patients from the LEOSS registry, 66 patients (1.6%) had a GI bleeding. The rate of GI bleeding in patients with intensive care unit (ICU) admission was 4.5%. The use of therapeutic dose of anticoagulants showed a significant association with the increased incidence of bleeding in the critical phase of disease. The Charlson comorbidity index and the COVID-19 severity index were significantly higher in the group of patients with GI bleeding than in the group of patients without GI bleeding (5.83 (SD = 2.93) vs. 3.66 (SD = 3.06), p < 0.01 and 3.26 (SD = 1.69) vs. 2.33 (SD = 1.53), p < 0.01, respectively). In the COKA registry 31 patients (2.5%) developed a GI bleeding. Of these, the source of bleeding was identified in upper GI tract in 21 patients (67.7%) with ulcer as the most frequent bleeding source (25.8%, n = 8) followed by gastroesophageal reflux (16.1%, n = 5). In three patients (9.7%) GI bleeding source was located in lower GI tract caused mainly by diverticular bleeding (6.5%, n = 2). In seven patients (22.6%) the bleeding localization remained unknown. CONCLUSION: Consistent with previous research, comorbidities and disease severity correlate with the incidence of GI bleeding. Also, therapeutic anticoagulation seems to be associated with a higher risk of GI bleeding. Overall, the risk of GI bleeding seems not to be increased in COVID-19 patients.

Neurological symptoms and complications in predominantly hospitalized COVID-19 patients: Results of the European multinational Lean European Open Survey on SARS-Infected Patients (LEOSS).

BACKGROUND AND PURPOSE: During acute coronavirus disease 2019 (COVID-19) infection, neurological signs, symptoms and complications occur. We aimed to assess their clinical relevance by evaluating real-world data from a multinational registry. METHODS: We analyzed COVID-19 patients from 127 centers, diagnosed between January 2020 and February 2021, and registered in the European multinational LEOSS (Lean European Open Survey on SARS-Infected Patients) registry. The effects of prior neurological diseases and the effect of neurological symptoms on outcome were studied using multivariate logistic regression. RESULTS: A total of 6537 COVID-19 patients (97.7% PCR-confirmed) were analyzed, of whom 92.1% were hospitalized and 14.7% died. Commonly, excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%) were reported. In patients with a complicated or critical disease course (53%) the most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (ICB; 2.2%). ICB peaked in the critical disease phase (5%) and was associated with the administration of anticoagulation and extracorporeal membrane oxygenation (ECMO). Excessive tiredness (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.20-1.68) and prior neurodegenerative diseases (OR 1.32, 95% CI 1.07-1.63) were associated with an increased risk of an unfavorable outcome. Prior cerebrovascular and neuroimmunological diseases were not associated with an unfavorable short-term outcome of COVID-19. CONCLUSION: Our data on mostly hospitalized COVID-19 patients show that excessive tiredness or prior neurodegenerative disease at first presentation increase the risk of an unfavorable short-term outcome. ICB in critical COVID-19 was associated with therapeutic interventions, such as anticoagulation and ECMO, and thus may be an indirect complication of a life-threatening systemic viral infection.

Microsomal activation of dibenzo[def,mno]chrysene (anthanthrene), a hexacyclic aromatic hydrocarbon without a bay-region, to mutagenic metabolites.

Metabolically formed dihydrodiol epoxides in the bay-region of polycyclic aromatic hydrocarbons are thought to be responsible for the genotoxic properties of these environmental pollutants. The hexacyclic aromatic hydrocarbon dibenzo[def,mno]chrysene (anthanthrene), although lacking this structural feature, was found to exhibit considerable bacterial mutagenicity in histidine-dependent strains TA97, TA98, TA100, and TA104 of S. typhimurium in the range of 18-40 his(+)-revertant colonies/nmol after metabolic activation with the hepatic postmitochondrial fraction of Sprague-Dawley rats treated with Aroclor 1254. This mutagenic effect amounted to 44-84% of the values determined with benzo[a]pyrene under the same conditions. The specific mutagenicity of anthanthrene in strain TA100 obtained with the cell fraction of untreated animals was 6 his(+)-revertant colonies/nmol and increased 2.7-fold after treatment with phenobarbital and 4.5-fold after treatment with 3-methylcholanthrene. To elucidate the metabolic pathways leading to genotoxic metabolites, the microsomal biotransformation of anthanthrene was investigated. A combination of chromatographic, spectroscopic, and biochemical methods allowed the identification of the trans-4,5-dihydrodiol, 4,5-oxide, 4,5-, 1,6-, 3,6-, and 6,12-quinones, and 1- and 3-phenols. Furthermore, two diphenols derived from the 3-phenol, possibly the 3,6 and 3,9 positional isomers, as well as two phenol dihydrodiols were isolated. Three pathways of microsomal biotransformation of anthanthrene could be distinguished: The K-region metabolites are formed via pathway I dominated by monooxygenases of the P450 1B subfamily. On pathway II the polynuclear quinones of anthanthrene are formed. Pathway III is preferentially catalyzed by monooxygenases of the P450 1A subfamily and leads to the mono- and diphenols of anthanthrene. The K-region oxide and the 3-phenol are the only metabolites of anthanthrene with strong intrinsic mutagenicity, qualifying them as ultimate mutagens or their precursors. From the intrinsic mutagenicity of these two metabolites and their metabolic formation, the maximal mutagenic effect was calculated. This demonstrates the dominating role of pathway III in the mutagenicity of anthanthrene under conditions where it exhibits the strongest bacterial mutagenicity.