The COVID-19 pandemic has starkly exposed queryPlease check author names and affiliation if presented correctly.vulnerabilities in the management of surveillance and testing. Significant challenges associated with physical tests, i.e., PCR and antigen tests, include their high cost, resource-intensive nature, turnaround time, and sensitivity. Although the literature has underscored the potential of Machine Learning-based methods for the digital diagnosis of COVID-19, developing high-performing models crucially depends on extensive datasets exceeding the amount available in one healthcare institution. Federated Machine Learning offers a solution to that dilemma. The aim of this research is to evaluate the potential impact of Federated Learning-based digital COVID-19 diagnosis on the trajectory of a pandemic. Therefore, we design a multidimensional evaluation framework, consisting of a simulation study utilizing real-world lab parameters from multiple hospitals and a newly developed performance indicator, named Testing Evaluation for Pandemics. We find that Federated Learning can significantly support the decision-making process of diagnosing COVID-19 at the beginning of a pandemic while saving scarce resources. However, a warm-up phase is needed until constant performance similar to physical tests is reached. In addition, lab parameters have a high prediction power for the diagnosis and are well suited because of patient welfare reasons.

BackgroundKlebsiella pneumoniae is one of the most important opportunistic pathogens causing healthcare-associated and community-acquired infections worldwide. In recent years, the increase in antibiotic resistance and infections caused by hypervirulent K. pneumoniae poses great public health concerns. In this study, host-pathogen interactions of different K. pneumoniae strains of human and animal origins were analyzed in microbiological, cell-biological and immunological experiments.MethodsIn vitro infection experiments using representatives of different K. pneumoniae pathotypes and various epithelial and macrophage cell lines were executed analyzing adhesion, invasion and intracellular replication. Experimental conditions involved normoxia and hypoxia. Furthermore, survival and growth of further K. pneumoniae isolates expressing defined siderophores in blood (platelet concentrates, serum) was investigated. All experiments were done in triplicate and statistically significant differences were determined.ResultsSignificant differences in adhesion and invasion capability, phagocytosis resistance and intracellular replication were measured between different K. pneumoniae pathotypes. Especially, ESBL-producing K. pneumoniae isolates demonstrated increased invasion in host cell lines and survival in macrophages. A strong cytotoxic effect on intestinal cells was observed for hypervirulent K. pneumoniae. The results from our investigations of the growth behavior of K. pneumoniae in platelets and serum showed that siderophores and/or an enlarged capsule are not essential factors for the proliferation of (hypervirulent) K. pneumoniae strains in blood components.ConclusionOur in vitro experiments revealed new insights into the host-pathogen interactions of K. pneumoniae strains representing different pathovars and clonal lineages in different infectious contexts and hosts. While a clear limitation of our study is the limited strain set used for both infection and as potential host, the results are a further step for a better understanding of the pathogenicity of K. pneumoniae and its properties essential for different stages of colonization and infection. When developed further, these results may offer novel approaches for future therapeutics including novel “anti-virulence strategies”.

Leuconostoc spp. are vancomycin-resistant Gram-positive cocci that are used in food production and as pre- and probiotics. However, Leuconostoc spp. can also cause infections. In the present study, the records of patients with Leuconostoc spp. detection between January 2012 and March 2025 were analyzed, inclusive of the underlying risk factors. Leuconostoc spp. was isolated from 32 patients (21 male, 11 females), including nine patients with blood culture evidence. In the majority of patients, Leuconostoc spp. were obtained on the day of admission to the hospital or in the first few days thereafter, arguing against nosocomial acquisition. The median age of men and women (65.3 and 67.8 years) was similar, but seven of the 14 male patients over the age of 65 had the bacteria in blood culture. The female patients with blood culture evidence had suffered from peripartum thrombophlebitis and from anorexia nervosa (BMI 8.8 kg/m2). In contrast, men with Leuconostoc spp. in the blood culture had severe, limiting underlying diseases. While the two women survived, five of the seven blood-culture-positive men died. Overall, our results show that Leuconostoc spp. is mainly acquired in outpatient settings, but men are at a higher risk of acquisition. Colonized men over the age of 60 with severe underlying diseases have a high risk of systemic infection with a fatal outcome.

Background & Aims Hepatitis E virus (HEV) is a main cause of acute hepatitis globally. However, immunosuppressed patients regularly develop chronic courses. The aim of this study was to analyse the current status of HEV diagnostics, characterize clinical manifestations and identify risk factors for complicated HEV infections. Methods In this retrospective study at two large hospitals, 512 patients with borderline and positive anti-HEV-IgM and 94 patients with positive HEV-PCR between January 1999 and May 2023 were included. Results Detection by anti-HEV-IgM-ELISA led to a positive HEV-PCR in only 17.9 %. Amongst patients with positive HEV-PCR, 61 had underlying immunosuppression and 23 were patients after solid organ transplantation (SOT). All 13 patients with chronic HEV infections were immunosuppressed. Generally, immunosuppression led to higher HEV-RNA concentrations and a higher probability of receiving immediate treatment. However, all fulminant courses with liver failure happened in patients without immunosuppression. Immunocompetent patients showed symptoms more frequently and primarily had higher bilirubin levels indicating more severe liver damage. A risk factor for delayed or failed viral clearance after SOT was the administration of mTOR inhibitors. Conclusions Fulminant HEV infections happen primarily in immunocompetent patients. Nevertheless, immunosuppressed patients bear the risk of undetected, prolonged HEV infections, reflected by the rare occurrence of symptoms.

ObjectivesTo investigate, whether inflammatory rheumatic diseases (IRD) inpatients are at higher risk to develop a severe course of SARS-CoV-2 infections compared to the general population, data from the German COVID-19 registry for IRD patients and data from the Lean European Survey on SARS-CoV-2 (LEOSS) infected patients covering inpatients from the general population with SARS-CoV-2 infections were compared.Methods4310 (LEOSS registry) and 1139 cases (IRD registry) were collected in general. Data were matched for age and gender. From both registries, 732 matched inpatients (LEOSS registry: n = 366 and IRD registry: n = 366) were included for analyses in total.ResultsRegarding the COVID-19 associated lethality, no significant difference between both registries was observed. Age > 65°years, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, spondyloarthritis and the use of rituximab were associated with more severe courses of COVID-19. Female gender and the use of tumor necrosis factor-alpha inhibitors (TNF-I) were associated with a better outcome of COVID-19.ConclusionInflammatory rheumatic diseases (IRD) patients have the same risk factors for severe COVID-19 regarding comorbidities compared to the general population without any immune-mediated disease or immunomodulation. The use of rituximab was associated with an increased risk for severe COVID-19. On the other hand, the use of TNF-I was associated with less severe COVID-19 compared to the general population, which might indicate a protective effect of TNF-I against severe COVID-19 disease.

Background: Klebsiella (K.) pneumoniae is a ubiquitous Gram-negative bacterium and a common coloniser of animals and humans. Today, K. pneumoniae is one of the most persistent nosocomial pathogens worldwide and poses a severe threat/burden to public health by causing urinary tract infections, pneumonia and bloodstream infections. Infections mainly affect immunocompromised individuals and hospitalised patients. In recent years, a new type of K. pneumoniae has emerged associated with community-acquired infections such as pyogenic liver abscess in otherwise healthy individuals and is therefore termed hypervirulent K. pneumoniae (hvKp). The aim of this study was the characterisation of K. pneumoniae isolates with properties of hypervirulence from Germany. Methods: A set of 62 potentially hypervirulent K. pneumoniae isolates from human patients was compiled. Inclusion criteria were the presence of at least one determinant that has been previously associated with hypervirulence: (I) clinical manifestation, (II) a positive string test as a marker for hypermucoviscosity, and (III) presence of virulence associated genes rmpA and/or rmpA2 and/or magA. Phenotypic characterisation of the isolates included antimicrobial resistance testing by broth microdilution. Whole genome sequencing (WGS) was performed using Illumina® MiSeq/NextSeq to investigate the genetic repertoire such as multi-locus sequence types (ST), capsule types (K), further virulence associated genes and resistance genes of the collected isolates. For selected isolates long-read sequencing was applied and plasmid sequences with resistance and virulence determinants were compared. Results: WGS analyses confirmed presence of several signature genes for hvKp. Among them, the most prevalent were the siderophore loci iuc and ybt and the capsule regulator genes rmpA and rmpA2. The most dominant ST among the hvKp isolates were ST395 capsule type K2 and ST395 capsule type K5; both have been described previously and were confirmed by our data as multidrug-resistant (MDR) isolates. ST23 capsule type K1 was the second most abundant ST in this study; this ST has been described as commonly associated with hypervirulence. In general, resistance to beta-lactams caused by the production of extended-spectrum beta-lactamases (ESBL) and carbapenemases was observed frequently in our isolates, confirming the threatening rise of MDR-hvKp strains. Conclusions: Our study results show that K. pneumoniae strains that carry several determinants of hypervirulence are present for many years in Germany. The detection of carbapenemase genes and hypervirulence associated genes on the same plasmid is highly problematic and requires intensified screening and molecular surveillance. However, the non-uniform definition of hvKp complicates their detection. Testing for hypermucoviscosity alone is not specific enough to identify hvKp. Thus, we suggest that the classification of hvKp should be applied to isolates that not only fulfil phenotypical criteria (severe clinical manifestations, hypermucoviscosity) but also (I) the presence of at least two virulence loci e.g. iuc and ybt, and (II) the presence of rmpA and/or rmpA2.

This study investigates the care provision and the role of infectious disease (ID) specialists during the coronavirus disease-2019 (COVID-19) pandemic. A survey was conducted at German study sites participating in the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS). Hospitals certified by the German Society of Infectious diseases (DGI) were identified as ID centers. We compared care provision and the involvement of ID specialists between ID and non-ID hospitals. Then we applied a multivariable regression model to analyse how clinical ID care influenced the mortality of COVID-19 patients in the LEOSS cohort. Of the 40 participating hospitals in the study, 35

INTRODUCTION:Active malignancies have been identified as an independent risk factor for severity and mortality in COVID-19. However, direct comparisons between SARS-CoV-2-infected patients with active (acP) and non-active cancers (n-acP) remain scarce. PATIENTS AND METHODS:We retrospectively analyzed a cohort of cancer patients with PCR-confirmed SARS-CoV-2 infection, enrolled from March 16, 2020, to July 31, 2021. Data on demographics, cancer, and laboratory findings were collected. Descriptive and subsequent regression analyses were performed. Endpoints were "deterioration to severe COVID-19" and "infection-associated mortality." RESULTS:In total, 987 cancer patients (510 acP vs. 477 n-acP) were included in our analysis. The majority was >55 years old, more men than women were included. At detection of SARS-CoV-2, 65.5% of patients had mild/moderate symptoms, while deterioration to severe COVID-19 was slightly more common in acP (19 vs. 16%; p = 0.284). COVID-19-associated mortality was significantly higher in acP (24 vs. 17.5%, p < 0.001). In terms of laboratory tests, severe cytopenia and elevated levels of inflammatory markers were common findings in acP at baseline, particularly in those who developed a severe infection or died. Multivariate analysis revealed that ferritin (HR 14.24 [2.1-96], p = 0.006) and CRP (HR 2.85 [1.02-8.02], p = 0.046) were associated with severity and mortality. In n-acP, association was seen for ferritin only (HR 4.1 [1.51-11.17], p = 0.006). CONCLUSION:Comparing patients with active and non-active cancer, the former showed higher mortality rates. Also, inflammatory markers were significantly increased, assuming higher levels of inflammation may play a role in the adverse outcome of COVID-19 in aCP.

(1) Background: Streptococcus dysgalactiae subspecies equisimilis (SDSE) is an important β-hemolytic pathogen historically described as mainly affecting animals. Studies epidemiologically assessing the pathogenicity in the human population in Germany are rare. (2) Methods: the present study combines national surveillance data from 2010 to 2022 with a single-center clinical study conducted from 2016 to 2022, focusing on emm type, Lancefield antigen, antimicrobial resistance, patient characteristics, disease severity, and clinical infection markers. (3) Results: The nationwide reported invasive SDSE infections suggest an increasing infection burden for the German population. One particular emm type, stG62647, increased over the study period, being the dominant type in both study cohorts, suggesting a mutation-driven outbreak of a virulent clone. The patient data show that men were more affected than women, although in the single-center cohort, this trend was reversed for patients with stG62647 SDSE. Men affected by stG62647 developed predominantly fascial infections, whereas women suffering from superficial and fascial non-stG62647 SDSE infections were significantly younger than other patients. Increasing age was a general risk factor for invasive SDSE infections. (4) Conclusions: further studies are needed to further elucidate the raised questions regarding outbreak origin, underlying molecular mechanisms as well as sex-dependent pathogen adaptation.

The Covid-19 pandemic has pushed many hospitals to their capacity limits. Therefore, a triage of patients has been discussed controversially primarily through an ethical perspective. The term triage contains many aspects such as urgency of treatment, severity of the disease and pre-existing conditions, access to critical care, or the classification of patients regarding subsequent clinical pathways starting from the emergency department. The determination of the pathways is important not only for patient care, but also for capacity planning in hospitals. We examine the performance of a human-made triage algorithm for clinical pathways which is considered a guideline for emergency departments in Germany based on a large multicenter dataset with over 4,000 European Covid-19 patients from the LEOSS registry. We find an accuracy of 28 percent and approximately 15 percent sensitivity for the ward class. The results serve as a benchmark for our extensions including an additional category of palliative care as a new label, analytics, AI, XAI, and interactive techniques. We find significant potential of analytics and AI in Covid-19 triage regarding accuracy, sensitivity, and other performance metrics whilst our interactive human-AI algorithm shows superior performance with approximately 73 percent accuracy and up to 76 percent sensitivity. The results are independent of the data preparation process regarding the imputation of missing values or grouping of comorbidities. In addition, we find that the consideration of an additional label palliative care does not improve the results.

For the fight against the COVID-19 pandemic, it is particularly important to map the course of infection, in terms of patients who have currently tested SARS-CoV-2 positive, as accurately as possible. In hospitals, this is even more important because resources have become scarce. Although polymerase chain reaction (PCR) and point of care (POC) antigen testing capacities have been massively expanded, they are often very time-consuming and cost-intensive and, in some cases, lack appropriate performance. To meet these challenges, we propose the COVIDAL classifier for AI-based diagnosis of symptomatic COVID-19 subjects in hospitals based on laboratory parameters. We evaluate the algorithm's performance by unique multicenter data with approximately 4,000 patients and an extraordinary high ratio of SARS-CoV-2-positive patients. We analyze the influence of data preparation, flexibility in optimization targets, as well as the selection of the test set on the COVIDAL outcome. The algorithm is compared with standard AI, PCR, POC antigen testing and manual classifications of seven physicians by a decision theoretic scoring model including performance metrics, turnaround times and cost. Thereby, we define health care settings in which a certain classifier for COVID-19 diagnosis is to be applied. We find sensitivities, specificities, and accuracies of the COVIDAL algorithm of up to 90 percent. Our scoring model suggests using PCR testing for a focus on performance metrics. For turnaround times, POC antigen testing should be used. If balancing performance, turnaround times, and cost is of interest, as, for example, in the emergency department, COVIDAL is superior based on the scoring model.

Abstract Introduction Studies investigating risk factors for severe COVID-19 often lack information on the representativeness of the study population. Here, we investigate factors associated with severe COVID-19 and compare the representativeness of the dataset to the general population. Methods We used data from the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) of hospitalized COVID-19 patients diagnosed in 2020 in Germany to identify associated factors for severe COVID-19, defined as progressing to a critical disease stage or death. To assess the representativeness, we compared the LEOSS cohort to cases of hospitalized patients in the German statutory notification data of the same time period. Descriptive methods and Poisson regression models were used. Results Overall, 6672 hospitalized patients from LEOSS and 132,943 hospitalized cases from the German statutory notification data were included. In LEOSS, patients above 76 years were less likely represented (34.3% vs. 44.1%). Moreover, mortality was lower (14.3% vs. 21.5%) especially among age groups above 66 years. Factors associated with a severe COVID-19 disease course in LEOSS included increasing age, male sex (adjusted risk ratio (aRR) 1.69, 95% confidence interval (CI) 1.53–1.86), prior stem cell transplantation (aRR 2.27, 95% CI 1.53–3.38), and an elevated C-reactive protein at day of diagnosis (aRR 2.30, 95% CI 2.03–2.62). Conclusion We identified a broad range of factors associated with severe COVID-19 progression. However, the results may be less applicable for persons above 66 years since they experienced lower mortality in the LEOSS dataset compared to the statutory notification data.

During the COVID-19 pandemic, large numbers of elderly, multimorbid people required treatment in intensive care units. This study investigated how the inherent patient factors age and comorbidity burden affected the treatment strategy and the outcome achieved. Retrospective analysis of data from intensive care patients enrolled in the Lean European Open Survey on SARS-CoV2-Infected Patients (LEOSS) cohort found that a patient’s age and comorbidity burden in fact influenced their mortality rate and the use of ventilation therapy. Evidence showed that advanced age and multimorbidity were associated with the restrictive use of invasive ventilation therapies, particularly ECMO. Geriatric patients with a high comorbidity burden were clustered in the sub-cohort of non-ventilated ICU patients characterized by a high mortality rate. The risk of death generally increased with older age and accumulating comorbidity burden. Here, the more aggressive an applied procedure, the younger the age in which a majority of patients died. Clearly, geriatric, multimorbid COVID-19 patients benefit less from invasive ventilation therapies. This implies the need for a holistic approach to therapy decisions, taking into account the patient’s wishes.

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.

Abstract Background and Objective International registries have reported high mortality rates in patients with liver disease and COVID‐19. However, the extent to which comorbidities contribute to excess COVID‐19 mortality in cirrhosis is controversial. Methods We used the multinational Lean European Open Survey on SARS‐CoV‐2‐infected patients (LEOSS) to identify patients with cirrhosis documented between March 2020 and March 2021, when the wild‐type and alpha variant were predominant. We compared symptoms, disease progression and mortality after propensity score matching (PSM) for age, sex, obesity, smoking status, and concomitant diseases. Mortality was also compared with that of patients with spontaneous bacterial peritonitis (SBP) without SARS‐CoV‐2 infection, a common bacterial infection and well‐described precipitator of acute‐on‐chronic liver failure. Results Among 7096 patients with SARS‐CoV‐2 infection eligible for analysis, 70 (0.99%) had cirrhosis, and all were hospitalized. Risk factors for severe COVID‐19, such as diabetes, renal disease, and cardiovascular disease were more frequent in patients with cirrhosis. Case fatality rate in patients with cirrhosis was 31.4% with the highest odds of death in patients older than 65 years (43.6% mortality; odds ratio [OR] 4.02; p = 0.018), Child‐Pugh class C (57.1%; OR 4.00; p = 0.026), and failure of two or more organs (81.8%; OR 19.93; p = 0.001). After PSM for demographics and comorbidity, the COVID‐19 case fatality of patients with cirrhosis did not significantly differ from that of matched patients without cirrhosis (28.8% vs. 26.1%; p = 0.644) and was similar to the 28‐day mortality in a comparison group of patients with cirrhosis and SBP (33.3% vs. 31.5%; p = 1.000). Conclusions In immunologically naïve patients with cirrhosis, mortality from wild‐type SARS‐CoV‐2 and the alpha variant is high and is largely determined by cirrhosis‐associated comorbidities and extrahepatic organ failure.

(1) Background: Between March 2020 and January 2022 severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) caused five infection waves in Europe. The first and the second wave was caused by wildtype SARS-CoV-2, while the following waves were caused by the variants of concern Alpha, Delta, and Omicron respectively. (2) Methods: In the present analysis, the first four waves were compared in Germany and the UK, in order to examine the COVID-19 epidemiology and its modulation by non-pharmaceutical interventions (NPI). (3) Results: The number of COVID-19 patients on intensive care units and the case fatality rate were used to estimate disease burden, the excess mortality to assess the net effect of NPI and other measures on the population. The UK was more severely affected by the first and the third wave while Germany was more affected by the second wave. The UK had a higher excess mortality during the first wave, afterwards the excess mortality in both countries was nearly identical. While most NPI were lifted in the UK in July 2021, the measures were kept and even aggravated in Germany. Nevertheless, in autumn 2021 Germany was much more affected, nearly resulting in a balanced sum of infections and deaths compared to the UK. Within the whole observation period, in Germany the number of COVID-19 patients on ICUs was up to four times higher than in the UK. Our results show that NPI have a limited effect on COVID-19 burden, seasonality plays a crucial role, and a higher virus circulation in a pre-wave situation could be beneficial. (4) Conclusions: Although Germany put much more effort and resources to fight the pandemic, the net balance of both countries was nearly identical, questioning the benefit of excessive ICU treatments and of the implementation of NPI, especially during the warm season.

Superinfections are a fundamental critical care problem, and their significance in severe COVID-19 cases needs to be determined. This study analyzed data from the Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort focusing on intensive care patients. A retrospective analysis of patient data from 840 cases of COVID-19 with critical courses demonstrated that co-infections were frequently present and were primarily of nosocomial origin. Furthermore, our analysis showed that invasive therapy procedures accompanied an increased risk for healthcare-associated infections. Non-ventilated ICU patients were rarely affected by secondary infections. The risk of infection, however, increased even when non-invasive ventilation was used. A further, significant increase in infection rates was seen with the use of invasive ventilation and even more so with extracorporeal membrane oxygenation (ECMO) therapy. The marked differences among ICU techniques used for the treatment of COVID-19-induced respiratory failure in terms of secondary infection risk profile should be taken into account for the optimal management of critically ill COVID-19 patients, as well as for adequate antimicrobial therapy.