Presence of hypervirulence-associated determinants in Klebsiella pneumoniae from hospitalised patients in Germany.

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.

Role and benefits of infectious diseases specialists in the COVID-19 pandemic: Multilevel analysis of care provision in German hospitals using data from the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) cohort.

PURPOSE: This study investigates the care provision and the role of infectious disease (ID) specialists during the coronavirus disease-2019 (COVID-19) pandemic. METHODS: 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. RESULTS: Of the 40 participating hospitals in the study, 35% (14/40) were identified as ID centers. Among those, clinical ID care structures were more commonly established, and ID specialists were always involved in pandemic management and the care of COVID-19 patients. Overall, 68% (27/40) of the hospitals involved ID specialists in the crisis management team, 78% (31/40) in normal inpatient care, and 80% (28/35) in intensive care. Multivariable analysis revealed that COVID-19 patients in ID centers had a lower mortality risk compared to those in non-ID centers (odds ratio: 0.61 (95% CI 0.40-0.93), p = 0.021). CONCLUSION: ID specialists played a crucial role in pandemic management and inpatient care.

Disease severity in hospitalized COVID-19 patients: comparing routine surveillance with cohort data from the LEOSS study in 2020 in Germany.

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.

Covid-19 triage in the emergency department 2.0: how analytics and AI transform a human-made algorithm for the prediction of clinical pathways.

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.

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.

Prediction of COVID-19 deterioration in high-risk patients at diagnosis: an early warning score for advanced COVID-19 developed by machine learning.

PURPOSE: While more advanced COVID-19 necessitates medical interventions and hospitalization, patients with mild COVID-19 do not require this. Identifying patients at risk of progressing to advanced COVID-19 might guide treatment decisions, particularly for better prioritizing patients in need for hospitalization. METHODS: We developed a machine learning-based predictor for deriving a clinical score identifying patients with asymptomatic/mild COVID-19 at risk of progressing to advanced COVID-19. Clinical data from SARS-CoV-2 positive patients from the multicenter Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS) were used for discovery (2020-03-16 to 2020-07-14) and validation (data from 2020-07-15 to 2021-02-16). RESULTS: The LEOSS dataset contains 473 baseline patient parameters measured at the first patient contact. After training the predictor model on a training dataset comprising 1233 patients, 20 of the 473 parameters were selected for the predictor model. From the predictor model, we delineated a composite predictive score (SACOV-19, Score for the prediction of an Advanced stage of COVID-19) with eleven variables. In the validation cohort (n = 2264 patients), we observed good prediction performance with an area under the curve (AUC) of 0.73 ± 0.01. Besides temperature, age, body mass index and smoking habit, variables indicating pulmonary involvement (respiration rate, oxygen saturation, dyspnea), inflammation (CRP, LDH, lymphocyte counts), and acute kidney injury at diagnosis were identified. For better interpretability, the predictor was translated into a web interface. CONCLUSION: We present a machine learning-based predictor model and a clinical score for identifying patients at risk of developing advanced COVID-19.

Development and validation of a simplified risk score for the prediction of critical COVID-19 illness in newly diagnosed patients.

Scores to identify patients at high risk of progression of coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may become instrumental for clinical decision-making and patient management. We used patient data from the multicentre Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) and applied variable selection to develop a simplified scoring system to identify patients at increased risk of critical illness or death. A total of 1946 patients who tested positive for SARS-CoV-2 were included in the initial analysis and assigned to derivation and validation cohorts (n = 1297 and n = 649, respectively). Stability selection from over 100 baseline predictors for the combined endpoint of progression to the critical phase or COVID-19-related death enabled the development of a simplified score consisting of five predictors: C-reactive protein (CRP), age, clinical disease phase (uncomplicated vs. complicated), serum urea, and D-dimer (abbreviated as CAPS-D score). This score yielded an area under the curve (AUC) of 0.81 (95% confidence interval [CI]: 0.77-0.85) in the validation cohort for predicting the combined endpoint within 7 days of diagnosis and 0.81 (95% CI: 0.77-0.85) during full follow-up. We used an additional prospective cohort of 682 patients, diagnosed largely after the "first wave" of the pandemic to validate the predictive accuracy of the score and observed similar results (AUC for the event within 7 days: 0.83 [95% CI: 0.78-0.87]; for full follow-up: 0.82 [95% CI: 0.78-0.86]). An easily applicable score to calculate the risk of COVID-19 progression to critical illness or death was thus established and validated.

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.

Clinical course and predictive risk factors for fatal outcome of SARS-CoV-2 infection in patients with chronic kidney disease.

PURPOSE: The ongoing pandemic caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2) has stressed health systems worldwide. Patients with chronic kidney disease (CKD) seem to be more prone to a severe course of coronavirus disease (COVID-19) due to comorbidities and an altered immune system. The study's aim was to identify factors predicting mortality among SARS-CoV-2-infected patients with CKD. METHODS: We analyzed 2817 SARS-CoV-2-infected patients enrolled in the Lean European Open Survey on SARS-CoV-2-infected patients and identified 426 patients with pre-existing CKD. Group comparisons were performed via Chi-squared test. Using univariate and multivariable logistic regression, predictive factors for mortality were identified. RESULTS: Comparative analyses to patients without CKD revealed a higher mortality (140/426, 32.9% versus 354/2391, 14.8%). Higher age could be confirmed as a demographic predictor for mortality in CKD patients (> 85 years compared to 15-65 years, adjusted odds ratio (aOR) 6.49, 95% CI 1.27-33.20, p = 0.025). We further identified markedly elevated lactate dehydrogenase (> 2 × upper limit of normal, aOR 23.21, 95% CI 3.66-147.11, p < 0.001), thrombocytopenia (< 120,000/µl, aOR 11.66, 95% CI 2.49-54.70, p = 0.002), anemia (Hb < 10 g/dl, aOR 3.21, 95% CI 1.17-8.82, p = 0.024), and C-reactive protein (≥ 30 mg/l, aOR 3.44, 95% CI 1.13-10.45, p = 0.029) as predictors, while renal replacement therapy was not related to mortality (aOR 1.15, 95% CI 0.68-1.93, p = 0.611). CONCLUSION: The identified predictors include routinely measured and universally available parameters. Their assessment might facilitate risk stratification in this highly vulnerable cohort as early as at initial medical evaluation for SARS-CoV-2.

First results of the "Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS)".

PURPOSE: Knowledge regarding patients' clinical condition at severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is sparse. Data in the international, multicenter Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort study may enhance the understanding of COVID-19. METHODS: Sociodemographic and clinical characteristics of SARS-CoV-2-infected patients, enrolled in the LEOSS cohort study between March 16, 2020, and May 14, 2020, were analyzed. Associations between baseline characteristics and clinical stages at diagnosis (uncomplicated vs. complicated) were assessed using logistic regression models. RESULTS: We included 2155 patients, 59.7% (1,287/2,155) were male; the most common age category was 66-85 years (39.6%; 500/2,155). The primary COVID-19 diagnosis was made in 35.0% (755/2,155) during complicated clinical stages. A significant univariate association between age; sex; body mass index; smoking; diabetes; cardiovascular, pulmonary, neurological, and kidney diseases; ACE inhibitor therapy; statin intake and an increased risk for complicated clinical stages of COVID-19 at diagnosis was found. Multivariable analysis revealed that advanced age [46-65 years: adjusted odds ratio (aOR): 1.73, 95% CI 1.25-2.42, p = 0.001; 66-85 years: aOR 1.93, 95% CI 1.36-2.74, p < 0.001; > 85 years: aOR 2.38, 95% CI 1.49-3.81, p < 0.001 vs. individuals aged 26-45 years], male sex (aOR 1.23, 95% CI 1.01-1.50, p = 0.040), cardiovascular disease (aOR 1.37, 95% CI 1.09-1.72, p = 0.007), and diabetes (aOR 1.33, 95% CI 1.04-1.69, p = 0.023) were associated with complicated stages of COVID-19 at diagnosis. CONCLUSION: The LEOSS cohort identified age, cardiovascular disease, diabetes and male sex as risk factors for complicated disease stages at SARS-CoV-2 diagnosis, thus confirming previous data. Further data regarding outcomes of the natural course of COVID-19 and the influence of treatment are required.

Findings from an outbreak of carbapenem-resistant Klebsiella pneumoniae emphasize the role of antibiotic treatment for cross transmission.

PURPOSE: In January 2015, we noticed by rectal swab analyses that seven of 23 patients at an early rehabilitation ward had been colonized with carbapenem-resistant Klebsiella pneumoniae (CKP). Here, we describe risk factors for CKP acquisition. METHODS: In the present study, the outbreak is described and risk factors for CKP acquisition are examined, e.g., antibiotic treatment. Microbiological analyses including corresponding results were examined to study when colonization with CKP occurred and whether patients had suffered from diarrhea. To examine whether spread of bacteria was clonal, multi-locus sequence typing as well as Xbal macrorestriction and pulsed-field gel electrophoresis was performed. The presence of carbapenmase was examined by PCR analysis. Through univariate analysis of risk factors in the small study sample, the role of antibiotic consumption, isolation procedures, patient's age, gender, and Barthel index on colonization was elucidated. RESULTS: Clonal spread of the novel sequence type (ST)2255 was identified. Additionally, one patient was colonized with Escherichia coli and Serratia marcescens, both resistant to carbapenems, while a further patient carried another carbapenem-resistant E. coli strain. In all isolates, carbapenemase gene bla OXA-48 was found to be located on a conjugative plasmid (60 kb), suggesting in vivo transmission from CKP to E. coli and S. marcescens. Univariate tests indicated that antibiotic treatment was the only risk factor showing a significant association with being colonized by CKP. In addition, the likelihood of diarrhea appeared to be higher in this group. Antibiotic treatment was associated with CKP colonization, whereas patients´ age, gender, Barthel index at admission, and residence with a CKP-colonized roommate were not. Diarrhea also seemed to support to distribution of CKP. CONCLUSIONS: In this small outbreak, antibiotic treatment seemed to be the predominant risk factor for monoclonal transmission of bla OXA-48 positive CKP.

Laboratory-based investigation of suspected mumps cases submitted to the German National Reference Centre for Measles, Mumps, and Rubella, 2008 to 2013.

From 2008 to 2013, sample sets from 534 patients displaying clinical symptoms of mumps were submitted to the German Reference Centre for Measles, Mumps and Rubella. Mumps virus infection was confirmed in 216 cases (40%) by PCR and/or serology. Confirmed cases were more frequently seen in male than in female patients (128 vs. 81); the age group predominantly affected was 15 to 29 years old (65%, median age: 26.4 years). The majority of the confirmed cases had a remote history of vaccination with one or two doses of a mumps-containing vaccine (69%). Our results indicate that mumps virus caused two outbreaks in Bavaria in 2008 and 2010/2011 and a third one in Lower Saxony in 2011. Mumps virus genotype G was preponderantly detected from 2008 to 2013. For 107 of the 216 patients with a confirmed mumps infection, we correlated the results from PCR and serology. PCR detected cases during the first week after onset of symptoms (74% positive results). PCR worked best with throat swabs and oral fluids (61% and 60% positive results, respectively). IgM was more reliable with a longer time after onset of symptoms (67%), but indirect IgM serology was of insufficient sensitivity for vaccinated mumps cases (30%); the IgM µ-capture assay detected more cases in this group. Mumps virus is able to initiate an infection in vaccinated patients (secondary vaccine failure, SVF) although it is unclear to what extent. Since SVF does occur in highly vaccinated populations and IgM will not increase to detectable levels in all SVF patients, we strongly recommend using PCR plus serology tests to avoid false-negative diagnoses in vaccinated individuals with clinical signs of mumps.

Multifunctional use of an operating theatre: is floor drainage posing an increased risk of infection?

INTRODUCTION: For transurethral urologic surgery floor drainage is necessary for disposal of large amounts of fluid; for skin incision surgery floor drainage is unnecessary. The presence of floor drainage in an operating theatre may have a negative impact on the surgical site infection (SSI) rate after skin incision surgery due to aerosol contamination. We examined whether multifunctional use of an operating theatre would increase the SSI rate after skin incision surgery. PATIENTS AND METHODS: Patients undergoing skin incision surgery on the kidney or prostate were prospectively divided into two groups with regard to operating theatre equipment. 272 patients were operated on in a theatre with floor drainage and 755 patients were operated on in a theatre without floor drainage. SSIs were categorized using the CDC classification and SSI rates in the two different theatres were determined. RESULTS: No statistically significant difference (p = 0.86) in SSI rates after kidney and prostate surgery was found for operations in theatres with (2.6%) and without floor drainage (2.8%). CONCLUSIONS: Multifunctional use of an operating theatre with floor drainage for transurethral and skin incision surgery does not increase SSI rates. Thus, multifunctional use of theatres with floor drainage might lead to a gain in flexibility in the use of operating theatre capacity.

Hepatitis E virus infection in immunosuppressed patients and its clinical manifestations.

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.

COVID-19 in Patients with Active Cancer: Higher Inflammatory Activity Predicts Poor Outcome.

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.

The protective effect of tumor necrosis factor-alpha inhibitors in COVID-19 in patients with inflammatory rheumatic diseases compared to the general population-A comparison of two German registries.

Objectives: To 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. Methods: 4310 (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. Results: Regarding 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. Conclusion: Inflammatory 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.

Meningitis in a pregnant woman caused by Streptococcus dysgalactiae subspecies equisimilis.

Infection of the central nervous system by streptococci is known to result in severe bacterial meningitis, however some strains have low pathogenic potential and affect the brain only in immunocompromised patients. Here we report the first case of an otherwise healthy non immunocompromised young adult woman who developed meningitis caused by Streptococcus dysgalactiae subspecies equisimilis. The patient was in the 17th week of her 3rd pregnancy. The course of the disease was quickly remittent under antibiotic treatment.

Epidemiological and Clinical Features of Streptococcus dysgalactiae ssp. equisimilis stG62647 and Other emm Types in Germany.

(1) Background: Streptococcus dysgalactiae subspecies equisimilis (SDSE) is an important ß-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.