Publications by authors named "Robert Krause"

212 Publications

Humoral immune response to Covid-19 vaccination in diabetes: age-dependent but independent of type of diabetes and glycaemic control - the prospective COVAC-DM cohort study.

Diabetes Obes Metab 2022 Jan 4. Epub 2022 Jan 4.

Interdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Austria.

Aims: Immune response to COVID-19 vaccination and a potential impact of glycaemia on antibody levels in people with diabetes remains unclear. We investigated the seroconversion following first and second COVID-19 vaccination in people with type 1 and type 2 diabetes in relation to glycaemic control prior to vaccination and analysed the response in comparison to individuals without diabetes.

Materials And Methods: This prospective, multicenter cohort study analysed people with type 1 and type 2 diabetes and an HbA1c ≤7.5% (58 mmol/mol) or >7.5% (58 mmol/mol), respectively and healthy controls. Roche's Elecsys anti-SARS-CoV-2 S immunoassay targeting the receptor-binding domain was used to quantify anti-spike protein antibodies 7-14 days after the first and 14-21 days after the second vaccination.

Results: 86 healthy controls and 161 participants with diabetes were enrolled, 150 (75 with type 1 diabetes and 75 with type 2 diabetes) were eligible for the analysis. After the first vaccination, only 52.7% in the type 1 diabetes group and 48.0% in the type 2 diabetes group showed antibody levels above the cut-off for positivity. Antibody levels after the second vaccination were similar in people with type1, type 2 diabetes and healthy controls if adjusted for age, sex and multiple testing (p>0.05). Age (r=-0.45, p<0.001) and glomerular filtration rate (r=0.28, p=0.001) were significantly associated with antibody response.

Conclusions: Anti-SARS-CoV-2 S receptor-binding domain antibody levels after the second vaccination were comparable in healthy controls, people with type 1 and type 2 diabetes, irrespective of glycaemic control. Age and renal function correlated significantly with the extent of antibody levels. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/dom.14643DOI Listing
January 2022

Investigation of Non-invasive Continuous Body Temperature Measurements in a Clinical Setting Using an Adhesive Axillary Thermometer (SteadyTemp®).

Front Digit Health 2021 14;3:794274. Epub 2021 Dec 14.

Department of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria.

Since the human body reacts to a variety of different diseases with elevated body temperature, measurement of body temperature remains relevant in clinical practice. The absolute temperature value for fever definition is still arbitrary and depends on the measuring site, as well as underlying disease and individual factors. Hence, a simple threshold for fever definition is outdated and a definition which relies on the relative changes in the individual seems reasonable as it takes these individual factors into account. In this prospective multicentric study we validate an adhesive axillary thermometer (SteadyTemp®) which allows continuous non-invasive temperature measurements. It consists of a patch to measure temperature and a smartphone application to process and visualize gathered data. This article provides information of the new diagnostic possibilities when using this wearable device and where it could be beneficial. Furthermore, it discusses how to interpret the generated data and when it is not practical to use, based on its characteristics and physiological phenomena.
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http://dx.doi.org/10.3389/fdgth.2021.794274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712449PMC
December 2021

Evaluation of a novel, rapid antigen detection test for the diagnosis of SARS-CoV-2.

PLoS One 2021 29;16(11):e0259527. Epub 2021 Nov 29.

Wiener Gesundheitsverbund, Vienna, Australia.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is currently finally determined in laboratory settings by real-time reverse-transcription polymerase-chain-reaction (rt-PCR). However, simple testing with immediately available results are crucial to gain control over COVID-19. The aim was to evaluate such a point-of-care antigen rapid test (AG-rt) device in its performance compared to laboratory-based rt-PCR testing in COVID-19 suspected, symptomatic patients.

Methods: For this prospective study, two specimens each of 541 symptomatic female (54.7%) and male (45.3%) patients aged between 18 and 95 years tested at five emergency departments (ED, n = 296) and four primary healthcare centres (PHC, n = 245), were compared, using AG-rt (positive/negative/invalid) and rt-PCR (positive/negative and cycle threshold, Ct) to diagnose SARS-CoV-2. Diagnostic accuracy, sensitivity, specificity, positive predictive values (PPV), negative predictive value (NPV), and likelihood ratios (LR+/-) of the AG-rt were assessed.

Results: Differences between ED and PHC were detected regarding gender, age, symptoms, disease prevalence, and diagnostic performance. Overall, 174 (32.2%) were tested positive on AG-rt and 213 (39.4%) on rt-PCR. AG correctly classified 91.7% of all rt-PCR positive cases with a sensitivity of 80.3%, specificity of 99.1%, PPV of 98.3, NPV of 88.6%, LR(+) of 87.8, and LR(-) of 0.20. The highest sensitivities and specificities of AG-rt were detected in PHC (sensitivity: 84.4%, specificity: 100.0%), when using Ct of 30 as cut-off (sensitivity: 92.5%, specificity: 97.8%), and when symptom onset was within the first three days (sensitivity: 82.9%, specificity: 99.6%).

Conclusions: The highest sensitivity was detected with a high viral load. Our findings suggest that AG-rt are comparable to rt-PCR to diagnose SARS-CoV-2 in COVID-19 suspected symptomatic patients presenting both at emergency departments and primary health care centres.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0259527PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8629250PMC
December 2021

ESCMID COVID-19 living guidelines: drug treatment and clinical management.

Clin Microbiol Infect 2021 Nov 22. Epub 2021 Nov 22.

Clinical Unit of Infectious Diseases and Microbiology Virgen Macarena University Hospital and Department of Medicine, University of Seville, Institute of Biomedicine of Seville, Seville, Spain.

Scope: In January 2021, the ESCMID Executive Committee decided to launch a new initiative to develop ESCMID guidelines on several COVID-19-related issues, including treatment of COVID-19.

Methods: An ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search with a third panellist involved in case of inconsistent results. Voting was based on the GRADE approach.

Questions Addressed By The Guideline And Recommendations: A synthesis of the available evidence and recommendations is provided for each of the 15 PICOs, which cover use of hydroxychloroquine, bamlanivimab alone or in combination with etesevimab, casirivimab combined with imdevimab, ivermectin, azithromycin and empirical antibiotics, colchicine, corticosteroids, convalescent plasma, favipiravir, remdesivir, tocilizumab and interferon β-1a, as well as the utility of antifungal prophylaxis and enoxaparin. In general, the panel recommended against the use of hydroxychloroquine, ivermectin, azithromycin, colchicine and interferon β-1a. Conditional recommendations were given for the use of monoclonal antibodies in high-risk outpatients with mild-moderate COVID-19, and remdesivir. There was insufficient evidence to make a recommendation for use of favipiravir and antifungal prophylaxis, and it was recommended that antibiotics should not be routinely prescribed in patients with COVID-19 unless bacterial coinfection or secondary infection is suspected or confirmed. Tocilizumab and corticosteroids were recommended for treatment of severe COVID-19 but not in outpatients with non-severe COVID-19.

Scope: The aim of the present guidance is to provide evidence-based recommendations for management of adults with coronavirus disease 2019 (COVID-19). More specifically, the goal is to aid clinicians managing patients with COVID-19 at various levels of severity including outpatients, hospitalized patients, and those admitted to intensive care unit. Considering the composition of the panel, mostly clinical microbiologists or infectious disease specialists with no pulmonology or intensive care background, we focus only on pharmacological treatment and do not give recommendations on oxygen supplement/support. Similarly, as no paediatricians were included in the panel; the recommendations are only for adult patients with COVID-19. Considering the current literature, no guidance was given for special populations such as the immunocompromised.
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http://dx.doi.org/10.1016/j.cmi.2021.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606314PMC
November 2021

The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.

Drugs 2021 Oct 9;81(15):1703-1729. Epub 2021 Oct 9.

Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, San Diego, CA, USA.

The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug-drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available over the last 2 decades, and only one single new agent from a known antifungal class has been approved in the last decade. Nevertheless, there is hope on the horizon, with a number of new antifungal classes in late-stage clinical development. In this review, we describe the mechanisms of drug resistance employed by fungi and extensively discuss the most promising drugs in development, including fosmanogepix (a novel Gwt1 enzyme inhibitor), ibrexafungerp (a first-in-class triterpenoid), olorofim (a novel dihyroorotate dehydrogenase enzyme inhibitor), opelconazole (a novel triazole optimized for inhalation), and rezafungin (an echinocandin designed to be dosed once weekly). We focus on the mechanism of action and pharmacokinetics, as well as the spectrum of activity and stages of clinical development. We also highlight the potential future role of these drugs and unmet needs.
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http://dx.doi.org/10.1007/s40265-021-01611-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501344PMC
October 2021

HIV status alters disease severity and immune cell responses in Beta variant SARS-CoV-2 infection wave.

Elife 2021 10 5;10. Epub 2021 Oct 5.

Africa Health Research Institute, Durban, South Africa.

There are conflicting reports on the effects of HIV on COVID-19. Here, we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (Beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV-negative participants. Higher disease severity was associated with low CD4 T cell counts and higher neutrophil to lymphocyte ratios (NLR). Yet, CD4 counts recovered and NLR stabilized after SARS-CoV-2 clearance in wave 2 infected PLWH, arguing for an interaction between SARS-CoV-2 and HIV infection leading to low CD4 and high NLR. The first infection wave, where severity in HIV negative and PLWH was similar, still showed some HIV modulation of SARS-CoV-2 immune responses. Therefore, HIV infection can synergize with the SARS-CoV-2 variant to change COVID-19 outcomes.
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http://dx.doi.org/10.7554/eLife.67397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8676326PMC
October 2021

Antifungal prophylaxis for prevention of COVID-19-associated pulmonary aspergillosis in critically ill patients: an observational study.

Crit Care 2021 09 15;25(1):335. Epub 2021 Sep 15.

Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Background: Coronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) emerged as important fungal complications in patients with COVID-19-associated severe acute respiratory failure (ARF). Whether mould active antifungal prophylaxis (MAFP) can prevent CAPA remains elusive so far.

Methods: In this observational study, we included all consecutive patients admitted to intensive care units with COVID-19-associated ARF between September 1, 2020, and May 1, 2021. We compared patients with versus without antifungal prophylaxis with respect to CAPA incidence (primary outcome) and mortality (secondary outcome). Propensity score adjustment was performed to account for any imbalances in baseline characteristics. CAPA cases were classified according to European Confederation of Medical Mycology (ECMM)/International Society of Human and Animal Mycoses (ISHAM) consensus criteria.

Results: We included 132 patients, of whom 75 (57%) received antifungal prophylaxis (98% posaconazole). Ten CAPA cases were diagnosed, after a median of 6 days following ICU admission. Of those, 9 CAPA cases were recorded in the non-prophylaxis group and one in the prophylaxis group, respectively. However, no difference in 30-day ICU mortality could be observed. Thirty-day CAPA incidence estimates were 1.4% (95% CI 0.2-9.7) in the MAFP group and 17.5% (95% CI 9.6-31.4) in the group without MAFP (p = 0.002). The respective subdistributional hazard ratio (sHR) for CAPA incidence comparing the MAFP versus no MAFP group was of 0.08 (95% CI 0.01-0.63; p = 0.017).

Conclusion: In ICU patients with COVID-19 ARF, antifungal prophylaxis was associated with significantly reduced CAPA incidence, but this did not translate into improved survival. Randomized controlled trials are warranted to evaluate the efficacy and safety of MAFP with respect to CAPA incidence and clinical outcomes.
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http://dx.doi.org/10.1186/s13054-021-03753-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441945PMC
September 2021

Implementation of a Dual-Column Liquid Chromatography-Tandem Mass-Spectrometry Method for the Quantification of Isavuconazole in Clinical Practice.

J Lab Physicians 2021 Jun 15;13(2):123-128. Epub 2021 Jun 15.

Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.

 Therapeutic drug monitoring (TDM) of isavuconazole, which is a novel broad-spectrum antimycoticum against invasive fungal infections, ensures an effective exposure of the drug and minimizes the risk of toxicity. This study is aimed at evaluating the analytical performance of a dual-column liquid chromatography-tandem mass-spectrometry (LC-MS/MS) method for isavuconazole quantification.  The method was performed on a Voyager TSQ Quantum triple quadrupole instrument equipped with an Ultimate 3000 chromatography system (Thermo Fisher Scientific, San Jose, California, United States). Analytical and preanalytical requirements of the isavuconazole LC-MS/MS method were evaluated. Sample stability measurements were performed at room temperature (RT) and in serum tubes with separator gel.  The isavuconazole LC-MS/MS method was linear over the concentration range of 0.2 to 12.8 mg/L. The coefficient of determination ( ) always exceeded 0.999. Within- and between-run precision ranged between 1.4 to 2.9% and 1.5 to 3.0%, the recovery between 93.9 and 102.7%. At RT, serum samples were stable for 3 days. Isavuconazole serum concentrations were significantly lower after incubation (18 hours) in serum tubes with separator gel at RT.  The dual-column isavuconazole LC-MS/MS is a reliable tool for the TDM of isavuconazole. Serum samples are stable for at least 3 days and should be collected in tubes without separator gel.
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http://dx.doi.org/10.1055/s-0041-1730755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409122PMC
June 2021

Similar antibody responses against SARS-CoV-2 in HIV uninfected and infected individuals on antiretroviral therapy during the first South African infection wave.

Clin Infect Dis 2021 Sep 2. Epub 2021 Sep 2.

HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa.

Background: There is limited understanding of SARS-CoV-2 pathogenesis in African populations with a high burden of infectious disease comorbidities such as HIV. The kinetics, magnitude and duration of virus-specific antibodies and the underlying B cell responses in people living with HIV (PLWH) in sub-Saharan Africa have not been fully characterized.

Methods: We longitudinally followed SARS-CoV-2 infected individuals in Durban, KwaZulu-Natal, South Africa and characterized SARS-CoV-2 receptor binding domain-specific IgM, IgG and IgA antibodies weekly for a month, and then at 3 months post diagnosis. 7/30 (41.7%) were PLWH, 83% (25/30) of which were on ART and with full HIV suppression. Potency of convalescent plasma neutralization was determined using a live virus neutralization assay and antibody secreting cell population frequencies were determined by flow cytometry.

Results: Similar seroconversion rates, time to peak antibody titer, peak magnitude and durability of anti-SARS-CoV-2 IgM, IgG, IgA, were observed in HIV uninfected and PLWH with complete HIV suppression on ART. In addition, similar neutralization potency against an isolate of SARS-CoV-2, circulating at the time of sampling in the first wave of SARS-CoV-2 infections in South Africa was observed in both groups. Loss of IgA was significantly associated with age (p=0.023) and a previous diagnosis of TB (p=0.018).

Conclusions: Similar antibody response kinetics and neutralization potency in HIV negative and PLWH on stable ART in an African setting suggests that COVID-19 natural infections may confer comparable antibody immunity in these groups. This provides hope that COVID-19 vaccines will be effective in PLWH on stable ART.
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http://dx.doi.org/10.1093/cid/ciab758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522359PMC
September 2021

Sensitivity and specificity of the antigen-based anterior nasal self-testing programme for detecting SARS-CoV-2 infection in schools, Austria, March 2021.

Euro Surveill 2021 08;26(34)

Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria.

This study evaluates the performance of the antigen-based anterior nasal screening programme implemented in all Austrian schools to detect SARS-CoV-2 infections. We combined nationwide antigen-based screening data obtained in March 2021 from 5,370 schools (Grade 1-8) with an RT-qPCR-based prospective cohort study comprising a representative sample of 244 schools. Considering a range of assumptions, only a subset of infected individuals are detected with the programme (low to moderate sensitivity) and non-infected individuals mainly tested negative (very high specificity).
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http://dx.doi.org/10.2807/1560-7917.ES.2021.26.34.2100797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393891PMC
August 2021

Long-lasting immune response to a mild course of PCR-confirmed SARS-CoV-2 infection: A cohort study.

J Infect 2021 11 22;83(5):607-635. Epub 2021 Aug 22.

Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz, Austria; BioTechMed-Graz, Graz, Austria.

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http://dx.doi.org/10.1016/j.jinf.2021.08.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380195PMC
November 2021

Enhanced survival of multi-species biofilms under stress is promoted by low-abundant but antimicrobial-resistant keystone species.

J Hazard Mater 2022 01 8;422:126836. Epub 2021 Aug 8.

Institute of Environmental Biotechnology, Graz University of Technology, Graz, Austria; BioTechMed Graz, Inter-university Cooperation Platform, Graz, Austria; Leibniz Institute for Agricultural Engineering and Bioeconomy (ATB), Potsdam, Germany; Institute for Biochemistry and Biology, University of Postdam, Postdam, Germany. Electronic address:

Multi-species biofilms are more resistant against stress compared to single-species biofilms. However, the mechanisms underlying this common observation remain elusive. Therefore, we studied biofilm formation of well-known opportunistic pathogens (Acinetobacter baumanii, Enterococcus faecium, Escherichia coli, Staphylococcus haemolyticus and Stenotrophomonas maltophilia) in various approaches. Synergistic effects in their multi-species biofilms were observed. Using metatranscriptomics, changes in the gene expression of the involved members became evident, and provided explanations for the improved survivability under nutrient limitation and exposure to disinfectants. Genes encoding proteins for vitamin B6 synthesis and iron uptake were linked to synergism in the multi-species biofilm under nutrient-limited conditions. Our study indicates that sub-lethal concentrations of an alcohol-based disinfectant enhance biofilm yields in multi-species assemblages. A reduction of the dominant taxa in the multi-species biofilm under disinfectant pressure allowed minor taxa to bloom. The findings underline the importance of minor but antimicrobial-resistant species that serve as "protectors" for the whole assemblage due to upregulation of genes involved in defence mechanisms and biofilm formation. This ultimately results in an increase in the total yield of the multi-species biofilm. We conclude that inter-species interactions may be crucial for the survival of opportunistic pathogens; especially under conditions that are typically found under hospital settings.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126836DOI Listing
January 2022

Analysis of COVID-19 outbreaks in 3 long-term care facilities in Graz, Austria.

Am J Infect Control 2021 11 15;49(11):1350-1353. Epub 2021 Aug 15.

Albert Schweitzer Hospital, Geriatric Health Centers of the City of Graz, Graz, Austria.

Background: Nursing homes and long-term care facilities (LTCF) caring for elderly and chronically ill residents are at high risk to experience severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) outbreaks. We report an outbreak of coronavirus disease 2019 (COVID-19) in 3 LTCFs of the Geriatric Health Centres of Graz, Austria lasting from March 22 to April 14, 2020.

Aim: The objectives of our study were: (1) to elucidate contributing factors and transmission pathways of SARS-CoV-2, (2) to analyze symptoms of COVID-19 in the residents and health care workers.

Methods: We carried out a retrospective outbreak analysis.

Findings: Thirty-six of /277 residents of 3 LTCFs were infected with SARS-CoV-2. Only a quarter of COVID-19 cases among residents had fever ≥38.1°C and 19% suffered from cough. Six of 36 residents remained asymptomatic. Hospitalization rate was 58% in residents. Overall, 33% (12/36) residents infected with SARS-CoV-2 died. Nineteen of 214 health care workers were tested positive for SARS-CoV-2. Universal rt-PCR testing for SARS-CoV-2 of all residents and health care workers as well as infection control measures contributed to ending the outbreaks.

Conclusions: Delayed recognition of possible COVID-19 cases due to either mild symptoms or symptoms that were perceived as atypical early in the pandemic contributed to the transmission of SARS-CoV-2 in LTCFs. This emphasizes the importance of low-threshold testing in LTCF residents.
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http://dx.doi.org/10.1016/j.ajic.2021.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364514PMC
November 2021

Prevalence of RT-qPCR-detected SARS-CoV-2 infection at schools: First results from the Austrian School-SARS-CoV-2 prospective cohort study.

Lancet Reg Health Eur 2021 Jun 23;5:100086. Epub 2021 Mar 23.

Centre for Microbiology and Environmental Systems Science, Department of Microbiology and Ecosystem Science, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.

Background: The role of schools in the SARS-CoV-2 pandemic is much debated. We aimed to quantify reliably the prevalence of SARS-CoV-2 infections at schools detected with reverse-transcription quantitative polymerase-chain-reaction (RT-qPCR).

Methods: This nationwide prospective cohort study monitors a representative sample of pupils (grade 1-8) and teachers at Austrian schools throughout the school year 2020/2021. We repeatedly test participants for SARS-CoV-2 infection using a gargling solution and RT-qPCR. We herein report on the first two rounds of examinations. We used mixed-effects logistic regression to estimate odds ratios and robust 95% confidence intervals (95% CI).

Findings: We analysed data on 10,734 participants from 245 schools (9465 pupils, 1269 teachers). Prevalence of SARS-CoV-2 infection increased from 0·39% at round 1 (95% CI 028-0·55%, 28 September-22 October 2020) to 1·39% at round 2 (95% CI 1·04-1·85%, 10-16 November). Odds ratios for SARS-CoV-2 infection were 2·26 (95% CI 1·25-4·12,  = 0·007) in regions with >500 vs. ≤500 inhabitants/km, 1·67 (95% CI 1·42-1·97, <0·001) per two-fold higher regional 7-day community incidence, and 2·78 (95% CI 1·73-4·48, <0·001) in pupils at schools with high/very high vs. low/moderate social deprivation. Associations of regional community incidence and social deprivation persisted in a multivariable adjusted model. Prevalence did not differ by average number of pupils per class nor between age groups, sexes, pupils vs. teachers, or primary (grade 1-4) vs. secondary schools (grade 5-8).

Interpretation: This monitoring study in Austrian schools revealed SARS-CoV-2 infection in 0·39%-1·39% of participants and identified associations of regional community incidence and social deprivation with higher prevalence.

Funding: BMBWF Austria.
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http://dx.doi.org/10.1016/j.lanepe.2021.100086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350968PMC
June 2021

Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology.

Lancet Infect Dis 2021 12 6;21(12):e364-e374. Epub 2021 Aug 6.

Department of Internal Medicine, Hospital Sultanah Bayiyah, Alor Setar, Kedah, Malaysia.

The global burden of the endemic mycoses (blastomycosis, coccidioidomycosis, emergomycosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, and talaromycosis) continues to rise yearly and these infectious diseases remain a leading cause of patient morbidity and mortality worldwide. Management of the associated pathogens requires a thorough understanding of the epidemiology, risk factors, diagnostic methods and performance characteristics in different patient populations, and treatment options unique to each infection. Guidance on the management of these infections has the potential to improve prognosis. The recommendations outlined in this Review are part of the "One World, One Guideline" initiative of the European Confederation of Medical Mycology. Experts from 23 countries contributed to the development of these guidelines. The aim of this Review is to provide an up-to-date consensus and practical guidance in clinical decision making, by engaging physicians and scientists involved in various aspects of clinical management.
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http://dx.doi.org/10.1016/S1473-3099(21)00191-2DOI Listing
December 2021

Explorative assessment of coronavirus-like short sequences from host-associated and environmental metagenomes.

Sci Total Environ 2021 Nov 24;793:148494. Epub 2021 Jun 24.

Graz University of Technology, Institute of Environmental Biotechnology, Graz, Austria; BioTechMed-Graz, Graz, Austria. Electronic address:

The ongoing COVID-19 pandemic has not only globally caused a high number of causalities, but is also an unprecedented challenge for scientists. False-positive virus detection tests not only aggravate the situation in the healthcare sector, but also provide ground for speculations. Previous studies have highlighted the importance of software choice and data interpretation in virome studies. We aimed to further expand theoretical and practical knowledge in bioinformatics-driven virome studies by focusing on short, virus-like DNA sequences in metagenomic data. Analyses of datasets obtained from different sample types (terrestrial, animal and human related samples) and origins showed that coronavirus-like sequences have existed in host-associated and environmental samples before the current COVID-19 pandemic. In the analyzed datasets, various Betacoronavirus-like sequences were detected that also included SARS-CoV-2 matches. Deepening analyses indicated that the detected sequences are not of viral origin and thus should not be considered in virome profiling approaches. Our study confirms the importance of parameter selection, especially in terms of read length, for reliable virome profiling. Natural environments are an important source of coronavirus-like nucleotide sequences that should be taken into account when virome datasets are analyzed and interpreted. We therefore suggest that processing parameters are carefully selected for SARS-CoV-2 profiling in host related as well as environmental samples in order to avoid incorrect identifications.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222970PMC
November 2021

Lewis and ABO histo-blood types and the secretor status of patients hospitalized with COVID-19 implicate a role for ABO antibodies in susceptibility to infection with SARS-CoV-2.

Transfusion 2021 09 26;61(9):2736-2745. Epub 2021 Jun 26.

Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz, Graz, Austria.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets the respiratory and gastric epithelium, causing coronavirus disease 2019 (COVID-19). Tissue antigen expression variations influence host susceptibility to many infections. This study aimed to investigate the closely linked Lewis (FUT3) and ABO histo-blood types, including secretor (FUT2) status, to infections with SARS-CoV-2 and the corresponding severity of COVID-19.

Study Design And Methods: Patients (Caucasians, n = 338) were genotyped for ABO, FUT3, and FUT2, and compared to a reference population of blood donors (n = 250,298). The association between blood types and severity of COVID-19 was addressed by dividing patients into four categories: hospitalized individuals in general wards, patients admitted to the intensive care unit with and without intubation, and deceased patients. Comorbidities were considered in subsequent analyses.

Results: Patients with blood type Lewis (a-b-) or O were significantly less likely to be hospitalized (odds ratio [OR] 0.669, confidence interval [CI] 0.446-0.971, OR 0.710, CI 0.556-0.900, respectively), while type AB was significantly more prevalent in the patient cohort (OR 1.519, CI 1.014-2.203). The proportions of secretors/nonsecretors, and Lewis a+ or Lewis b+ types were consistent between patients and controls. The analyzed blood groups were not associated with the clinical outcome as defined.

Discussion: Blood types Lewis (a-b-) and O were found to be protective factors, whereas the group AB is suggested to be a risk factor for COVID-19. The antigens investigated may not be prognostic for disease severity, but a role for ABO isoagglutinins in SARS-CoV-2 infections is strongly suggested.
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http://dx.doi.org/10.1111/trf.16567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447157PMC
September 2021

Prospective Surveillance of Healthcare-Associated Infections in Residents in Four Long-Term Care Facilities in Graz, Austria.

Antibiotics (Basel) 2021 May 7;10(5). Epub 2021 May 7.

Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.

Healthcare-associated infections (HCAI) are a common cause for residents' mortality and morbidity associated with a significant socio-economic burden. Data on HCAIs in Austrian long-term care facilities are scare. Therefore, we evaluated the incidence rate of HCAIs per 1000 resident days in four LTC facilities in Graz, Austria, characterized the spectrum of HCAIs and the use of antimicrobial substances. We conducted a prospective surveillance study from 1 January to 31 December 2018 in four LTCFs of the Geriatric Health Centre of the City of Graz (total of 388 beds). Nursing staff collected data on HCAIs once a week using an electronic reporting system. During the 12-month surveillance period, 252 infections of 165 residents were recorded. The overall incidence rate of HCAIs was 2.1 per 1000 resident days. Urinary tract infections were the most commonly recorded HCAIs (49%, 124/252, 1.03 per 1000 resident days), followed by skin and soft tissue infections and respiratory tract infections. Beta-lactams (ATC class J01C) were prescribed most frequently (63/212), followed by fluoroquinolones (J01M; 54/212). In conclusion, the overall incidence rate for HCAIs was relatively low at 2.1 per 1000 resident days. Our real-life data can serve as a basis for future antimicrobial stewardship and infection prevention interventions.
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http://dx.doi.org/10.3390/antibiotics10050544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151996PMC
May 2021

Convalescent plasma therapy and mortality in COVID-19 patients admitted to the ICU: a prospective observational study.

Ann Intensive Care 2021 May 12;11(1):73. Epub 2021 May 12.

Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Background: This study aimed to quantify the potential survival benefit of convalescent plasma therapy (CVP) in critically ill patients with acute respiratory failure related to coronavirus disease-2019 (COVID-19).

Methods: This is a single-center prospective observational cohort study in COVID-19 patients with acute respiratory failure. Immediately after intensive care unit (ICU) admission patients were allocated to CVP treatment following pre-specified criteria to rapidly identify those patients potentially susceptible for this treatment. A propensity score adjustment [inverse probability of treatment weighted (IPTW) analysis] was implemented to account rigorously for imbalances in prognostic variables between the treatment groups.

Results: We included 120 patients of whom 48 received CVP. Thirty percent were female with a median age of 66 years [25th-75th percentile 54-75]. Eighty-eight percent of patients presented with severe acute respiratory failure as displayed by a median paO/FiO ratio (Horowitz Index) of 92 [77-150]. All patients required any kind of ventilatory support with more than half of them (52%) receiving invasive ventilation. Thirty-day ICU overall survival (OS) was 69% in the CVP group and 54% in the non-CVP group (log-rank p = 0.049), respectively. After weighing the time-to-event data for the IPTW, the favorable association between CVP and OS became even stronger (log-rank p = 0.035). Moreover, an exploratory analysis showed an overall survival benefit of CVP therapy for patients with non-invasive ventilation (Hazard ratio 0.12 95% CI 0.03-0.57, p = 0.007) CONCLUSION: Administration of CVP in patients with acute respiratory failure related to COVID-19 is associated with improved ICU survival rates.
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http://dx.doi.org/10.1186/s13613-021-00867-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114671PMC
May 2021

Genetic Diversity of in Rodents and Human Patients in Austria, 2012-2019.

Viruses 2021 04 8;13(4). Epub 2021 Apr 8.

Center for Virology, Medical University of Vienna, 1090 Vienna, Austria.

(PUUV) has a wide distribution throughout Europe. Distinctive temporal patterns of spillover into the human population are related to population dynamics of the reservoir host, the bank vole (). As the rodent host is tied to specific habitats with small individual ranges, PUUV genetic diversity is also highly correlated with geographic distance. Using sequenced portions of viral S and M segments, we determined whether geographic clusters were supported. Human cases of PUUV infections are concentrated in southeastern Austria. We detected four distinct genotypes: two genotypes of the Alpe-Adria (ALAD) lineage typically associated with southeast Europe, and two sublineages of the Central Europe (CE) lineage. One cluster of CE genotypes represents a phylogenetically distinct sublineage compared to previously reported CE clades, and extends the boundary of the CE lineage further south than previously reported.
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http://dx.doi.org/10.3390/v13040640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069475PMC
April 2021

SARS-CoV-2 re-infection risk in Austria.

Eur J Clin Invest 2021 Apr 21;51(4):e13520. Epub 2021 Feb 21.

Austrian Agency for Health and Food Safety (AGES), Vienna, Austria.

Background: A key question concerning coronavirus disease 2019 (COVID-19) is how effective and long lasting immunity against this disease is in individuals who were previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to evaluate the risk of SARS-CoV-2 re-infections in the general population in Austria.

Methods: This is a retrospective observational study using national SARS-CoV-2 infection data from the Austrian epidemiological reporting system. As the primary outcome, we aim to compare the odds of SARS-CoV-2 re-infections of COVID-19 survivors of the first wave (February to April 30, 2020) versus the odds of first infections in the remainder general population by tracking polymerase chain reaction (PCR)-confirmed infections of both groups during the second wave from September 1 to November 30, 2020. Re-infection counts are tentative, since it cannot be excluded that the positive PCR in the first and/or second wave might have been a false positive.

Results: We recorded 40 tentative re-infections in 14 840 COVID-19 survivors of the first wave (0.27%) and 253 581 infections in 8 885 640 individuals of the remaining general population (2.85%) translating into an odds ratio (95% confidence interval) of 0.09 (0.07 to 0.13).

Conclusions: We observed a relatively low re-infection rate of SARS-CoV-2 in Austria. Protection against SARS-CoV-2 after natural infection is comparable with the highest available estimates on vaccine efficacies. Further well-designed research on this issue is urgently needed for improving evidence-based decisions on public health measures and vaccination strategies.
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http://dx.doi.org/10.1111/eci.13520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988582PMC
April 2021

Longitudinal Evaluation of Plasma Cytokine Levels in Patients with Invasive Candidiasis.

J Fungi (Basel) 2021 Feb 1;7(2). Epub 2021 Feb 1.

Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.

Interleukin (IL) 17A plays a decisive role in anti- host defense. Previous data demonstrated significantly increased IL-17A values in candidemic patients. We evaluated levels and time courses of IL-17A, and other cytokines suggested to be involved in -specific immunity (IL-6, IL-8, IL-10, IL-17F, IL-22, IL-23, interferon-γ, tumor necrosis factor-α, Pentraxin-related protein 3, transforming growth factor-β) in patients with invasive candidiasis (IC) compared to bacteremic patients (, ) and healthy controls (from previous 4 days up to day 14 relative to the index culture (-4; 14)). IL-17A levels were significantly elevated in all groups compared to healthy controls. In IC, the highest IL-17A values were measured around the date of index sampling (-1; 2), compared to significantly lower levels prior and after sampling the index culture. Candidemic patients showed significantly higher IL-17A values compared to IC other than candidemia at time interval (-1; 2) and (3; 7). No significant differences in IL-17A levels could be observed for IC compared to bacteremic patients. Candidemic patients had higher IL-8, IL-10, IL-22, IFN-γ, PTX3 and TNF-α values compared to non-candidemic. Based on the limited discriminating competence between candidemia and bacteremia, IL-17A has to be considered a biomarker for blood stream infection rather than invasive infection.
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http://dx.doi.org/10.3390/jof7020101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912850PMC
February 2021

Autopsy Proven Pulmonary Mucormycosis Due to in a Critically Ill COVID-19 Patient with Underlying Hematological Malignancy.

J Fungi (Basel) 2021 Jan 27;7(2). Epub 2021 Jan 27.

Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.

Viral infections can cause acute respiratory distress syndrome (ARDS), consequently leading to susceptibility for secondary pulmonary infections. Over the past few weeks, a number of studies have reported on secondary pulmonary aspergillosis complicating severe COVID-19. We report the case of a 53-year old male patient with secondary acute myeloid leukemia (AML) who suffered from COVID-19 ARDS and was diagnosed postmortem with mucormycosis.
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http://dx.doi.org/10.3390/jof7020088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912223PMC
January 2021

Social networks influence farming practices and agrarian sustainability.

PLoS One 2021 7;16(1):e0244619. Epub 2021 Jan 7.

Basque Centre for Climate Change, Leioa, Spain.

The social-ecological effects of agricultural intensification are complex. We explore farmers' perceptions about the impacts of their land management and the impact of social information flows on their management through a case study in a farming community in Navarra, Spain, that is undergoing agricultural intensification due to adoption of large scale irrigation. We found that modern technology adopters are aware that their management practices often have negative social-ecological implications; by contrast, more traditional farmers tend to recognize their positive impacts on non-material benefits such as those linked with traditions and traditional knowledge, and climate regulation. We found that farmers' awareness about nature contributions to people co-production and their land management decisions determine, in part, the structure of the social networks among the farming community. Since modern farmers are at the core of the social network, they are better able to control the information flow within the community. This has important implications, such as the fact that the traditional farmers, who are more aware of their impacts on the environment, rely on information controlled by more intensive modern farmers, potentially jeopardizing sustainable practices in this region. We suggest that this might be counteracted by helping traditional farmers obtain information tailored to their practices from outside the social network.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244619PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790232PMC
May 2021

Implementation of rapid antimicrobial susceptibility testing combined with routine infectious disease bedside consultation in clinical practice (RAST-ID): a prospective single-centre study.

J Antimicrob Chemother 2021 01;76(1):233-238

Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria.

Objectives: Recently, EUCAST released guidelines for rapid antimicrobial susceptibility testing (RAST) directly from positive blood culture bottles. The aim of our prospective single-centre clinical study was to assess the proportion of readable results and errors compared with routine antimicrobial susceptibility testing and the clinical consequences drawn by infectious disease (ID) physicians from RAST results during same-day bedside consultation.

Methods: All positive blood cultures suitable for RAST from January to December 2019 were included and RAST results at 4 and 6 h compared with standard disc diffusion. The real-life impact of RAST on clinical decisions was assessed during same-day ID bedside consultation.

Results: The proportion of readable RAST results was significantly higher after 6 h of incubation compared with after 4 h (881/930 versus 642/847; P < 0.0001). Major and very major errors were rare (17/642 after 4 h and 12/881 after 6 h; P = 0.087). ID consultation was performed in 134 patients after the RAST result. Antimicrobial treatment was changed in 73 patients and 84 additional measures (i.e. imaging studies, surgery, additional resistance testing) were ordered in 62 patients.

Conclusions: RAST according to EUCAST methods was easy to implement with a low number of major and very major errors after 6 h of incubation. ID physicians performing bedside consultations frequently used this information to change antimicrobial treatment and recommended additional measures.
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http://dx.doi.org/10.1093/jac/dkaa380DOI Listing
January 2021

Efficacy of universal preoperative decolonization with Polyhexanide in primary joint arthroplasty on surgical site infections. A multicenter before-and after-study.

Antimicrob Resist Infect Control 2020 11 30;9(1):188. Epub 2020 Nov 30.

Institute of Hygiene and Environmental Medicine, Charité-Universitätsmedizin Berlin, Hindenburgdamm 27, 12203, Berlin, Germany.

Background: Surgical site infections (SSI) are rare but severe complications after total joint arthroplasty (TJA). Decolonization measures prior to elective orthopedic surgeries have shown to reduce the risk of SSI with Staphylococcus aureus (S. aureus).

Objective: To determine the efficacy of universal decolonization with Polyhexanide on SSI rates with a focus on Staphylococcus aureus in patients with TJA.

Methods: Patients scheduled for elective hip or knee TJA in 5 participating certified orthopedic centers were included between 2015 and 2018 into this before and after study. Data on patients, surgeries and infections were prospectively collected. CDC-criteria were used to define and categorize Infections within 90 days after surgery. From January 2017 on, patients received decolonization sets containing Polyhexanide. Patients performed a 5 day decolonization regimen starting 4 days prior to surgery which included wipes, nasal decontamination and oral solution.

Results: Thirteen thousand, three hundred fifteen patients received TJA. During intervention 4437 decolonization sets were distributed among 7175 patients. Overall SSI rates increased from 0.68 /100 surgeries to 0.91/ 100 surgeries after implementation of the intervention (IRR 1.32; 95% CI 0.90-1.96). Time series analysis identified an increasing trend of SSI prior to the intervention. After implementation overall SSI rates plateaued. Regression analysis revealed surgery during intervention period to be an independent risk factor for developing a SSI (OR 1.34; 95%CI 1.18-1.53). Initial SSI rates due to S. aureus were 0.24/100 surgeries and decreased to 0.14/100 surgeries (IRR 0.57; 95% CI 0.25-1.22) after introduction of decolonization. Regression analysis revealed surgery during intervention period to be an independent protective factor for developing a SSI with S. aureus (OR 0.57, 95% CI: 0.33-0.99). Overall deep S. aureus SSI decreased significantly from 0.22/100 surgeries to 0.00/100 surgeries in patients adherent to protocol (IRR 0.00, 95% CI 0.00-.85).

Conclusion: Universal decolonization with Polyhexanide did not reduce overall surgical site infections, but was effective in reducing Staphylococcus aureus - surgical site infections following elective joint arthroplasty. Polyhexanide could extend the list of alternatives to already established decolonization strategies.

Trial Registration: The trial was registered at the German Registry for clinical studies www.drks.de ( DRKS00011505 ).
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http://dx.doi.org/10.1186/s13756-020-00852-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708093PMC
November 2020

Clinical and Radiographic Outcome of Gap Balancing Versus Measured Resection Techniques in Total Knee Arthroplasty.

Arthroplast Today 2020 Dec 5;6(4):835-844. Epub 2020 Oct 5.

Department of Orthopedic Surgery and Traumatology, UZ Brussel, Brussels, Belgium.

Background: There is no consensus regarding superiority between gap balancing (GB) and measured resection (MR) techniques to implant total knee arthroplasties. In a multicenter setup, we compared both techniques using the same prosthesis.

Methods: We included 262 balanSys posterior-stabilized total knee arthroplasties from 4 centers: 3 using the MR (n = 162) and one using the GB technique (n = 100), without navigation.

Results: There was no significant difference in the Knee Society Score or visual analog scale pain at 2- and 7-year follow-up. The visual analog scale for satisfaction was significantly better in the MR group at 2 but not at 7 years. We found a significantly higher average valgus in the GB group, but the overall alignment was within 2° of neutral on the full-leg radiographs. There were no significant differences concerning radiolucency and survival.

Conclusions: We found no significant differences in the functional outcome, pain, alignment, or survival, but a tendency toward better function using MR and better survival with GB.
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http://dx.doi.org/10.1016/j.artd.2020.07.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551640PMC
December 2020
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