Incidence and risk factors for HIV-tuberculosis coinfection in the Cologne-Bonn region: a retrospective cohort study.

PURPOSE: The risk of developing active tuberculosis (TB) is considerably increased in people living with HIV/AIDS (PLWH). However, incidence of HIV/TB coinfection is difficult to assess as surveillance data are lacking in many countries. Here, we aimed to perform a quantitative analysis of HIV/TB coinfections within the Cologne/Bonn HIV cohort and to determine risk factors for active TB. METHODS: We systematically evaluated data of patients with HIV/TB coinfection between 2006 and 2017. In this retrospective analysis, we compared HIV/TB-coinfected patients with a cohort of HIV-positive patients. The incidence density rate (IDR) was calculated for active TB cases at different time points. RESULTS: During 2006-2017, 60 out of 4673 PLWH were diagnosed with active TB. Overall IDR was 0.181 cases/100 patient-years and ranged from 0.266 in 2006-2009 to 0.133 in 2014-2017. Patients originating from Sub-Saharan Africa had a significantly (p < 0.001) higher IDR (0.694/100 patient-years of observation, 95% CI [0.435-1.050]) in comparison to patients of German origin (0.053/100 patient-years of observation, 95% CI [0.028-0.091]). In terms of TB-free survival, individuals originating from countries with a TB incidence higher than 10/100,000 exhibited a markedly reduced TB-free survival compared to those originating from regions with lower incidence (p < 0.001). In 22 patients, TB and HIV infection were diagnosed simultaneously. CONCLUSION: Overall, we observed a decline in the incidence density rate (IDR) of HIV/TB coinfections between 2006 and 2017. Patients originating from regions with high incidence bear a higher risk of falling ill with active TB. For PLWH born in Germany, the observed risk of active TB appears to be lower compared to other groups within the cohort. These findings should be considered when developing TB containment and screening strategies for PLWH in low-incidence countries.

Use and effectiveness of remdesivir for the treatment of patients with covid-19 using data from the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS): a multicentre cohort study.

OBJECTIVES: The use of remdesivir (RDV) as the first drug approved for coronavirus disease 2019 (COVID-19) remains controversial. Based on the Lean European Open Survey on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected patients (LEOSS), we aim to contribute timing-focused complementary real-world insights to its evaluation. METHODS: SARS-CoV-2 infected patients between January 2020 and December 2021 treated with RDV were matched 1:1 to controls considering sociodemographics, comorbidities and clinical status. Multiple imputations were used to account for missing data. Effects on fatal outcome were estimated using uni- and multivariable Cox regression models. RESULTS: We included 9,687 patients. For those starting RDV administration in the complicated phase, Cox regression for fatal outcome showed an adjusted hazard ratio (aHR) of 0.59 (95%CI 0.41-0.83). Positive trends could be obtained for further scenarios: an aHR of 0.51 (95%CI 0.16-1.68) when RDV was initiated in uncomplicated and of 0.76 (95% CI 0.55-1.04) in a critical phase of disease. Patients receiving RDV with concomitant steroids exhibited a further reduction in aHR in both, the complicated (aHR 0.50, 95%CI 0.29-0.88) and critical phase (aHR 0.63, 95%CI 0.39-1.02). CONCLUSION: Our study results elucidate that RDV use, in particular when initiated in the complicated phase and accompanied by steroids is associated with improved mortality. However, given the limitations of non-randomized trials in estimating the magnitude of the benefit of an intervention, further randomized trials focusing on the timing of therapy initiation seem warranted.

Specialized palliative care for hospitalized patients with SARS-CoV-2 infection: an analysis of the LEOSS registry.

PURPOSE: Symptom control for patients who were severely ill or dying from COVID-19 was paramount while resources were strained and infection control measures were in place. We aimed to describe the characteristics of SARS-CoV-2 infected patients who received specialized palliative care (SPC) and the type of SPC provided in a larger cohort. METHODS: From the multi-centre cohort study Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS), data of patients hospitalized with SARS-CoV-2 infection documented between July 2020 and October 2021 were analysed. RESULTS: 273/7292 patients (3.7%) received SPC. Those receiving SPC were older and suffered more often from comorbidities, but 59% presented with an estimated life expectancy > 1 year. Main symptoms were dyspnoea, delirium, and excessive tiredness. 224/273 patients (82%) died during the hospital stay compared to 789/7019 (11%) without SPC. Symptom control was provided most common (223/273; 95%), followed by family and psychological support (50% resp. 43%). Personal contact with friends or relatives before or during the dying phase was more often documented in patients receiving SPC compared to patients without SPC (52% vs. 30%). CONCLUSION: In 3.7% of SARS-CoV-2 infected hospitalized patients, the burden of the acute infection triggered palliative care involvement. Besides complex symptom management, SPC professionals also focused on psychosocial and family issues and aimed to enable personal contacts of dying patients with their family. The data underpin the need for further involvement of SPC in SARS-CoV-2 infected patients but also in other severe chronic infectious diseases.

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.

Herding Cats in Pandemic Times - Towards Technological and Organizational Convergence of Heterogeneous Solutions for Investigating and Mastering the Pandemic in University Medical Centers.

To understand and handle the COVID-19 pandemic, digital tools and infrastructures were built in very short timeframes, resulting in stand-alone and non-interoperable solutions. To shape an interoperable, sustainable, and extensible ecosystem to advance biomedical research and healthcare during the pandemic and beyond, a short-term project called "Collaborative Data Exchange and Usage" (CODEX+) was initiated to integrate and connect multiple COVID-19 projects into a common organizational and technical framework. In this paper, we present the conceptual design, provide an overview of the results, and discuss the impact of such a project for the trade-off between innovation and sustainable infrastructures.

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.

Age and Comorbidity Burden of Patients Critically Ill with COVID-19 Affect Both Access to and Outcome of Ventilation Therapy in Intensive Care Units.

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.

Staphylococcus aureus surgical site infection rates in 5 European countries.

OBJECTIVE: To determine the overall and procedure-specific incidence of surgical site infections (SSI) caused by Staphylococcus aureus (S. aureus) as well as risk factors for such across all surgical disciplines in Europe. METHODS: This is a retrospective cohort of patients with surgical procedures performed at 14 European centres in 2016, with a nested case-control analysis. S. aureus SSI were identified by a semi-automated crossmatching bacteriological and electronic health record data. Within each surgical procedure, cases and controls were matched using optimal propensity score matching. RESULTS: A total of 764 of 178 902 patients had S. aureus SSI (0.4%), with 86.0% of these caused by methicillin susceptible and 14% by resistant pathogens. Mean S. aureus SSI incidence was similar for all surgical specialties, while varying by procedure. CONCLUSIONS: This large procedure-independent study of S. aureus SSI proves a low overall infection rate of 0.4% in this cohort. It provides proof of principle for a semi-automated approach to utilize big data in epidemiological studies of healthcare-associated infections. Trials registration The study was registered at clinicaltrials.gov under NCT03353532 (11/2017).

Invasiveness of Ventilation Therapy Is Associated to Prevalence of Secondary Bacterial and Fungal Infections in Critically Ill COVID-19 Patients.

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.

Statistical biases due to anonymization evaluated in an open clinical dataset from COVID-19 patients.

Anonymization has the potential to foster the sharing of medical data. State-of-the-art methods use mathematical models to modify data to reduce privacy risks. However, the degree of protection must be balanced against the impact on statistical properties. We studied an extreme case of this trade-off: the statistical validity of an open medical dataset based on the German National Pandemic Cohort Network (NAPKON), which was prepared for publication using a strong anonymization procedure. Descriptive statistics and results of regression analyses were compared before and after anonymization of multiple variants of the original dataset. Despite significant differences in value distributions, the statistical bias was found to be small in all cases. In the regression analyses, the median absolute deviations of the estimated adjusted odds ratios for different sample sizes ranged from 0.01 [minimum = 0, maximum = 0.58] to 0.52 [minimum = 0.25, maximum = 0.91]. Disproportionate impact on the statistical properties of data is a common argument against the use of anonymization. Our analysis demonstrates that anonymization can actually preserve validity of statistical results in relatively low-dimensional data.