Publications by authors named "Christoph D Spinner"

78 Publications

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

Infection 2021 Jul 19. Epub 2021 Jul 19.

Institute for Infectious Diseases and Infection Control, RG Systemsbiology, Jena University Hospital, Kollegiengasse 10, 07743, Jena, Germany.

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.
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http://dx.doi.org/10.1007/s15010-021-01656-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287547PMC
July 2021

The impact of the SARS-CoV-2 pandemic on the prevalence of respiratory tract pathogens in patients with community-acquired pneumonia in Germany.

Emerg Microbes Infect 2021 Jul 16:1-8. Epub 2021 Jul 16.

Institute of Virology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

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http://dx.doi.org/10.1080/22221751.2021.1957402DOI Listing
July 2021

Use of monoclonal antibody therapy for nosocomial SARS-CoV-2 infection in patients at high risk for severe COVID-19: experience from a tertiary-care hospital in Germany.

Infection 2021 Jul 9. Epub 2021 Jul 9.

Department of Internal Medicine II, School of Medicine, University Hospital Rechts der Isar, Technical University of Munich, Munich, Germany.

Additional treatment options for coronavirus disease (COVID-19) are urgently needed, particularly for populations at high risk of severe disease. This cross-sectional, retrospective study characterized the outcomes of 43 patients with nosocomial severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with and without treatment using monoclonal SARS-CoV-2 spike antibodies (bamlanivimab or casirivimab/imdevimab). Our results indicate that treatment with monoclonal antibodies results in a significant decrease in disease progression and mortality when used for asymptomatic patients with early SARS-CoV-2 infection.
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http://dx.doi.org/10.1007/s15010-021-01657-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269399PMC
July 2021

COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma.

Hemasphere 2021 Jul 28;5(7):e603. Epub 2021 Jun 28.

Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Department of Internal Medicine II, Munich, Germany.

The clinical and immunological impact of B-cell depletion in the context of coronavirus disease 2019 (COVID-19) is unclear. We conducted a prospectively planned analysis of COVID-19 in patients who received B-cell depleting anti-CD20 antibodies and chemotherapy for B-cell lymphomas. The control cohort consisted of age- and sex-matched patients without lymphoma who were hospitalized because of COVID-19. We performed detailed clinical analyses, in-depth cellular and molecular immune profiling, and comprehensive virological studies in 12 patients with available biospecimens. B-cell depleted lymphoma patients had more severe and protracted clinical course (median hospitalization 88 versus 17 d). All patients actively receiving immunochemotherapy (n = 5) required ICU support including long-term mechanical ventilation. Neutrophil recovery following granulocyte colony stimulating factor stimulation coincided with hyperinflammation and clinical deterioration in 4 of the 5 patients. Immune cell profiling and gene expression analysis of peripheral blood mononuclear cells revealed early activation of monocytes/macrophages, neutrophils, and the complement system in B-cell depleted lymphoma patients, with subsequent exacerbation of the inflammatory response and dysfunctional interferon signaling at the time of clinical deterioration of COVID-19. Longitudinal immune cell profiling and functional in vitro assays showed SARS-CoV-2-specific CD8 and CD4 T-effector cell responses. Finally, we observed long-term detection of SARS-CoV-2 in respiratory specimens (median 84 versus 12 d) and an inability to mount lasting SARS-CoV-2 antibody responses in B-cell depleted lymphoma patients. In summary, we identified clinically relevant particularities of COVID-19 in lymphoma patients receiving B-cell depleting immunochemotherapies.
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http://dx.doi.org/10.1097/HS9.0000000000000603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240782PMC
July 2021

Key summary of German national treatment guidance for hospitalized COVID-19 patients Key pharmacologic recommendations from a national German living guideline using an Evidence to Decision Framework (last updated 17.05.2021).

Infection 2021 Jul 6. Epub 2021 Jul 6.

Department of Intensive Care, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Purpose: This executive summary of a national living guideline aims to provide rapid evidence based recommendations on the role of drug interventions in the treatment of hospitalized patients with COVID-19.

Methods: The guideline makes use of a systematic assessment and decision process using an evidence to decision framework (GRADE) as recommended standard WHO (2021). Recommendations are consented by an interdisciplinary panel. Evidence analysis and interpretation is supported by the CEOsys project providing extensive literature searches and living (meta-) analyses. For this executive summary, selected key recommendations on drug therapy are presented including the quality of the evidence and rationale for the level of recommendation.

Results: The guideline contains 11 key recommendations for COVID-19 drug therapy, eight of which are based on systematic review and/or meta-analysis, while three recommendations represent consensus expert opinion. Based on current evidence, the panel makes strong recommendations for corticosteroids (WHO scale 5-9) and prophylactic anticoagulation (all hospitalized patients with COVID-19) as standard of care. Intensified anticoagulation may be considered for patients with additional risk factors for venous thromboembolisms (VTE) and a low bleeding risk. The IL-6 antagonist tocilizumab may be added in case of high supplemental oxygen requirement and progressive disease (WHO scale 5-6). Treatment with nMABs may be considered for selected inpatients with an early SARS-CoV-2 infection that are not hospitalized for COVID-19. Convalescent plasma, azithromycin, ivermectin or vitamin D should not be used in COVID-19 routine care.

Conclusion: For COVID-19 drug therapy, there are several options that are sufficiently supported by evidence. The living guidance will be updated as new evidence emerges.
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http://dx.doi.org/10.1007/s15010-021-01645-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259552PMC
July 2021

Assessment of effective mitigation and prediction of the spread of SARS-CoV-2 in Germany using demographic information and spatial resolution.

Math Biosci 2021 Jun 30;339:108648. Epub 2021 Jun 30.

Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology (BRICS), Helmholtz Centre for Infection Research, Braunschweig, Germany. Electronic address:

Non-pharmaceutical interventions (NPIs) are important to mitigate the spread of infectious diseases as long as no vaccination or outstanding medical treatments are available. We assess the effectiveness of the sets of non-pharmaceutical interventions that were in place during the course of the Coronavirus disease 2019 (Covid-19) pandemic in Germany. Our results are based on hybrid models, combining SIR-type models on local scales with spatial resolution. In order to account for the age-dependence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we include realistic prepandemic and recently recorded contact patterns between age groups. The implementation of non-pharmaceutical interventions will occur on changed contact patterns, improved isolation, or reduced infectiousness when, e.g., wearing masks. In order to account for spatial heterogeneity, we use a graph approach and we include high-quality information on commuting activities combined with traveling information from social networks. The remaining uncertainty will be accounted for by a large number of randomized simulation runs. Based on the derived factors for the effectiveness of different non-pharmaceutical interventions over the past months, we provide different forecast scenarios for the upcoming time.
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http://dx.doi.org/10.1016/j.mbs.2021.108648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243656PMC
June 2021

Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial.

Lancet HIV 2021 07;8(7):e397-e407

Technical University of Munich, Munich, Germany.

Background: In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up.

Methods: This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov, number NCT02842086.

Findings: Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07-0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17-0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23-1·26]). Approximately 78-82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p<0·0001).

Interpretation: Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men.

Funding: Gilead Sciences.
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http://dx.doi.org/10.1016/S2352-3018(21)00071-0DOI Listing
July 2021

Hepatitis C virus: Current steps toward elimination in Germany and barriers to reaching the 2030 goal.

Health Sci Rep 2021 Jun 4;4(2):e290. Epub 2021 Jun 4.

First Department of Medicine University Medical Centre of the Johannes Gutenberg-University Mainz Germany.

Hepatitis C virus (HCV) affects over 70 million people globally, with an estimated 399 000 HCV-related deaths in 2016. The World Health Organization (WHO) has set a goal to eliminate HCV by 2030. Despite the availability of direct-acting antivirals-highly effective and well-tolerated therapies for HCV-many patients infected with HCV in Germany have not initiated treatment, including a majority of those who are aware of their positive diagnosis. Barriers to screening, diagnosis, and treatment are major factors taking many countries off track for HCV elimination by 2030. Identifying country-specific barriers and challenges, particularly in at-risk populations such as people who inject drugs or men who have sex with men, has the potential to create tailored programs and strategies to increase access to screening or treatment and engage at-risk populations. This review aims to report the current steps toward HCV elimination in Germany, the country-specific barriers and challenges that will potentially prevent reaching the 2030 HCV elimination goal and describe good practice examples to overcome these barriers.
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http://dx.doi.org/10.1002/hsr2.290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177898PMC
June 2021

Increased extravascular lung water index (EVLWI) reflects rapid non-cardiogenic oedema and mortality in COVID-19 associated ARDS.

Sci Rep 2021 06 1;11(1):11524. Epub 2021 Jun 1.

Department of Internal Medicine II, School of Medicine, University Hospital Rechts Der Isar, Technical University of Munich, Ismaninger Straße 22, 81675, Munich, Germany.

Nearly 5% of patients suffering from COVID-19 develop acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study, we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to COVID-19 negative, ventilated patients with ARDS and whether EVLWI has the potential to monitor disease progression. EVLWI and cardiac function were monitored by transpulmonary thermodilution in 25 patients with COVID-19 ARDS subsequent to intubation and compared to a control group of 49 non-COVID-19 ARDS patients. At intubation, EVLWI was noticeably elevated and significantly higher in COVID-19 patients than in the control group (17 (11-38) vs. 11 (6-26) mL/kg; p < 0.001). High pulmonary vascular permeability index values (2.9 (1.0-5.2) versus 1.9 (1.0-5.2); p = 0.003) suggested a non-cardiogenic pulmonary oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable in both cohorts. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and in-hospital mortality (23.2 ± 6.7% vs. 30.3 ± 6.0%, p = 0.025). Also, EVLWI showed a significant between-subjects (r = - 0.60; p = 0.001) and within-subjects correlation (r = - 0.27; p = 0.028) to Horowitz index. Compared to non COVID-19 ARDS, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. High EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 ARDS and could serve as parameter to monitor ARDS progression on ICU.
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http://dx.doi.org/10.1038/s41598-021-91043-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169693PMC
June 2021

Remdesivir for Early COVID-19 Treatment of High-Risk Individuals Prior to or at Early Disease Onset-Lessons Learned.

Viruses 2021 05 22;13(6). Epub 2021 May 22.

Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Department of Internal Medicine II, 81675 Munich, Germany.

After more than one year of the COVID-19 pandemic, antiviral treatment options against SARS-CoV-2 are still severely limited. High hopes that had initially been placed on antiviral drugs like remdesivir have so far not been fulfilled. While individual case reports provide striking evidence for the clinical efficacy of remdesivir in the right clinical settings, major trials failed to demonstrate this. Here, we highlight and discuss the key findings of these studies and underlying reasons for their failure. We elaborate on how such shortcomings should be prevented in future clinical trials and pandemics. We suggest in conclusion that any novel antiviral agent that enters human trials should first be tested in a post-exposure setting to provide rapid and solid evidence for its clinical efficacy before initiating further time-consuming and costly clinical trials for more advanced disease. In the COVID-19 pandemic this might have established remdesivir early on as an efficient antiviral agent at a more suitable disease stage which would have saved many lives, in particular in large outbreaks within residential care homes.
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http://dx.doi.org/10.3390/v13060963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224666PMC
May 2021

Reconvalescent plasma/camostat mesylate in early SARS-CoV-2 Q-PCR positive high-risk individuals (RES-Q-HR): a structured summary of a study protocol for a randomized controlled trial.

Trials 2021 May 17;22(1):343. Epub 2021 May 17.

Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Duesseldorf, Medical Faculty Heinrich-Heine-University Duesseldorf, Moorenstr. 5, D-40225, Duesseldorf, Germany.

Objectives: Currently, there are no approved treatments for early disease stages of COVID-19 and few strategies to prevent disease progression after infection with SARS-CoV-2. The objective of this study is to evaluate the safety and efficacy of convalescent plasma (CP) or camostat mesylate administered within 72 h of diagnosis of SARS-CoV-2 infection in adult individuals with pre-existing risk factors at higher risk of getting seriously ill with COVID-19. Camostat mesylate acts as an inhibitor of the host cell serine protease TMPRSS2 and prevents the virus from entering the cell. CP represents another antiviral strategy in terms of passive immunization. The working hypothesis to be tested in the RES-Q-HR study is that the early use of CP or camostat mesylate reduces the likelihood of disease progression to (modified) WHO stages 4b-8 in SARS-CoV-2-positive adult patients at high risk of moderate or severe COVID-19 progression.

Trial Design: This study is a 4-arm (parallel group), multicenter, randomized (2:2:1:1 ratio), partly double-blind, controlled trial to evaluate the safety and efficacy of convalescent plasma (CP) or camostat mesylate with control or placebo in adult patients diagnosed with SARS-CoV-2 infection and high risk for progression to moderate/severe COVID-19. Superiority of the intervention arms will be tested.

Participants: The trial is conducted at 10-15 tertiary care centers in Germany. Individuals aged 18 years or above with ability to provide written informed consent with SARS-CoV-2 infection, confirmed by PCR within 3 days or less before enrolment and the presence of at least one SARS-CoV-2 symptom (such as fever, cough, shortness of breath, sore throat, headache, fatigue, smell/and or taste disorder, diarrhea, abdominal symptoms, exanthema) and symptom duration of not more than 3 days. Further inclusion criteria comprise: Presence of at least one of the following criteria indicating increased risk for severe COVID-19: Age > 75 years Chronic obstructive pulmonary disease (COPD) and/or pulmonary fibrosis BMI > 40 kg/m Age > 65 years with at least one other risk factor (BMI > 35 kg/m, coronary artery disease (CAD), chronic kidney disease (CKD) with GFR < 60 ml/min but ≥ 30 ml/min, diabetes mellitus, active tumor disease) BMI > 35 kg/m with at least one other risk factor (CAD, CKD with GFR < 60 ml/min but ≥ 30 ml/min, diabetes mellitus, active tumor disease) Exclusion criteria: 1. Age < 18 years 2. Unable to give informed consent 3. Pregnant women or breastfeeding mothers 4. Previous transfusion reaction or other contraindication to a plasma transfusion 5. Known hypersensitivity to camostat mesylate and/or severe pancreatitis 6. Volume stress due to CP administration would be intolerable 7. Known IgA deficiency 8. Life expectancy < 6 months 9. Duration SARS-CoV-2 typical symptoms > 3 days 10. SARS-CoV-2 PCR detection older than 3 days 11. SARS-CoV-2 associated clinical condition ≥ WHO stage 3 (patients hospitalized for other reasons than COVID-19 may be included if they fulfill all inclusion and none of the exclusion criteria) 12. Previously or currently hospitalized due to SARS-CoV-2 13. Previous antiviral therapy for SARS-CoV-2 14. ALT or AST > 5 x ULN at screening 15. Liver cirrhosis > Child A (patients with Child B/C cirrhosis are excluded from the trial) 16. Chronic kidney disease with GFR < 30 ml/min 17. Concurrent or planned anticancer treatment during trial period 18. Accommodation in an institution due to legal orders (§40(4) AMG). 19. Any psycho-social condition hampering compliance with the study protocol. 20. Evidence of current drug or alcohol abuse 21. Use of other investigational treatment within 5 half-lives of enrolment is prohibited 22. Previous use of convalescent plasma for COVID-19 23. Concomitant proven influenza A infection 24. Patients with organ or bone marrow transplant in the three months prior to screening visit INTERVENTION AND COMPARATOR: Participants will be randomized to the following 4 groups: 1) Convalescent plasma (CP), 2 units at screening/baseline visit (day 0) or day 1; CP is defined by the presence of neutralizing anti-SARS-CoV-2 antibodies with titers ≥ 1:160; individuals with body weight ≥ 150 kg will receive a third unit of plasma on day 3 2) Camostat mesylate (200 mg per capsule, one capsule taken each in the morning, afternoon and evening on days 1-7) 3) Standard of care (SOC, control for CP) 4) Placebo (identical in appearance to camostat mesylate capsules, one capsule taken each morning, afternoon and evening on days 1-7; for camostat mesylate control group) Participants will be monitored after screening/baseline on day 3, day 5, day 8, and day 14. On day 28 and day 56, telephone visits and on day 90, another outpatient visit are scheduled. Adverse events and serious adverse events will be monitored and reported until the end of the study. An independent data safety monitoring committee will review trial progression and safety.

Main Outcomes: The primary endpoint of the study is the cumulative number of individuals who progress to or beyond category 4b on the modified WHO COVID-19 ordinal scale (defined as hospitalization with COVID-19 pneumonia and additional oxygen demand via nasal cannula or mask) within 28 days after randomization.

Randomization: Participants will be randomized using the Alea-Tool ( aleaclinical.com ) in a 2:2:1:1 ratio to the treatment arms (1) CP, (2) camostat mesylate, (3) standard of care (SoC), and (4) placebo matching camostat mesylate. Randomization will be stratified by study center.

Blinding (masking): The camostat mesylate treatment arm and the respective placebo will be blinded for participants, caregivers, and those assessing outcomes. The treatment arms convalescent plasma and standard of care will not be blinded and thus are open-labeled, unblinded.

Numbers To Be Randomized (sample Size): Overall, n = 994 participants will be randomized to the following groups: n = 331 to convalescent plasma (CP), n = 331 to camostat mesylate, n = 166 to standard of care (SoC), and n = 166 to placebo matching camostat mesylate.

Trial Status: The RES-Q-HR protocol (V04F) was approved on the 18 December 2020 by the local ethics committee and by the regulatory institutions PEI/BfARM on the 2 December 2020. The trial was opened for recruitment on 26 December 2020; the first patient was enrolled on 7 January 2021 and randomized on 8 January 2021. Recruitment shall be completed by June 2021. The current protocol version RES-Q HR V05F is from 4 January 2021, which was approved on the 18 January 2021.

Trial Registration: EudraCT Number 2020-004695-18 . Registered on September 29, 2020. ClinicalTrial.gov NCT04681430 . Registered on December 23, 2020, prior to the start of the enrollment (which was opened on December 26, 2020).

Full Protocol: The full protocol (V05F) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).
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http://dx.doi.org/10.1186/s13063-021-05181-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127198PMC
May 2021

Self-sampling versus health care professional-guided swab collection for SARS-CoV-2 testing.

Infection 2021 May 10. Epub 2021 May 10.

Department of Internal Medicine II, School of Medicine, University Hospital Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.

Purpose: To evaluate the diagnostic reliability and practicability of self-collected oropharyngeal swab samples for the detection of SARS-CoV-2 infection as self-sampling could enable broader testing availability and reduce both personal protective equipment and potential exposure.

Methods: Hospitalized SARS-CoV-2-infected patients were asked to collect two oropharyngeal swabs (SC-OPS1/2), and an additional oropharyngeal swab was collected by a health care professional (HCP-OPS). SARS-CoV-2 PCR testing for samples from 58 participants was performed, with a 48-h delay in half of the self-collected samples (SC-OPS2). The sensitivity, probability of concordance, and interrater reliability were calculated. Univariate and multivariate analyses were performed to assess predictive factors. Practicability was evaluated through a questionnaire.

Results: The test sensitivity for HCP-OPS, SC-OPS1, and SC-OPS2 was 88%, 78%, and 77%, respectively. Combining both SC-OPS results increased the estimated sensitivity to 88%. The concordance probability between HCP-OPS and SC-OPS1 was 77.6% and 82.5% between SC-OPS1 and SC-OPS2, respectively. Of the participants, 69% affirmed performing future self-sampling at home, and 34% preferred self-sampling over HCP-guided testing. Participants with both positive HCP-OPS1 and SC-OPS1 indicating no challenges during self-sampling had more differences in viral load levels between HCP-OPS1 and SC-OPS1 than those who indicated challenges. Increasing disease duration and the presence of anti-SARS-CoV-2-IgG correlated with negative test results in self-collected samples of previously confirmed SARS-CoV-2 positive individuals.

Conclusion: Oropharyngeal self-sampling is an applicable testing approach for SARS-CoV-2 diagnostics. Self-sampling tends to be more effective in early versus late infection and symptom onset, and the collection of two distinct samples is recommended to maintain high test sensitivity.
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http://dx.doi.org/10.1007/s15010-021-01614-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107404PMC
May 2021

Rapid clinical evolution for COVID-19 translates into early hospital admission and unfavourable outcome: a preliminary report.

Multidiscip Respir Med 2021 Jan 2;16(1):744. Epub 2021 Apr 2.

Department of Anaesthesiology and Intensive Care Medicine, University hospital rechts der Isar, Technical University of Munich, School of Medicine, Munich.

Background: A wide range of mortality rates has been reported in COVID-19 patients on the intensive care unit. We wanted to describe the clinical course and determine the mortality rate in our institution's intensive care units.

Methods: To this end, we performed a retrospective cohort study of 50 COVID-19 patients admitted to the ICU at a large German tertiary university hospital. Clinical features are reported with a focus on ICU interventions, such as mechanical ventilation, prone positioning and extracorporeal organ support. Outcome is presented using a 7-point ordinal scale on day 28 and 60 following ICU admission.

Results: The median age was 64 years, 78% were male. LDH and D-Dimers were elevated, and patients were low on Vitamin D. ARDS incidence was 75%, and 43/50 patients needed invasive ventilation. 22/50 patients intermittently needed prone positioning, and 7/50 required ECMO. The interval from onset of the first symptoms to admission to the hospital and to the ICU was shorter in non-survivors than in survivors. By day 60 after ICU admission, 52% of the patients had been discharged. 60-day mortality rate was 32%; 37% for ventilated patients, and 42% for those requiring both: ventilation and renal replacement therapy.

Conclusions: Early deterioration might be seen as a warning signal for unfavourable outcome. Lung-protective ventilation including prone positioning remain the mainstay of the treatment.
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http://dx.doi.org/10.4081/mrm.2021.744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056325PMC
January 2021

Health-related quality-of-life in people living with HIV after switching to dual therapy with ritonavir-boosted darunavir + dolutegravir: a DUALIS sub-study.

AIDS Care 2021 Apr 25:1-10. Epub 2021 Apr 25.

Department of Psychosomatic Medicine and Psychotherapy, Klinik Barmelweid AG, Barmelweid, Switzerland.

The DUALIS study demonstrated efficacy and safety of switching to dolutegravir plus ritonavir-boosted darunavir (DRV/r) (2DR) as compared to standard-of-care-therapy with two nucleoside reverse transcriptase inhibitors + DRV/r (3DR) in pretreated people living with HIV (PLWH), 48 weeks after switching. This DUALIS sub-study investigates health-related-quality-of-life (HrQoL) in this study-population. The Hospital Anxiety and Depression Scale (HADS) and the Medical Outcome Survey-HIV (MOS-HIV) were used assessing anxiety and depression symptoms, respectively HrQoL. Data were collected at baseline, 4, 24, and 48 weeks after randomization. Outcome scores were dichotomized and used as criteria in longitudinal models identifying differential developments. Odds ratios (ORs) with 95% confidence intervals (CIs) were computed as main measures of effects. ORs<1 indicate better results for HADS, and worse for MOS-HIV scores in the 2DR compared to 3DR group. In total, 263 subjects were randomized and treated (2DR n=131, 3DR n=132; median age 48 years). Significant different progressions could only be found for HADS-Depression scores (OR=.87, 95% CI: .78, .98, =.02). While HADS-Depression scores decreased in the 2DR group, they increased in 3DR group. This sub-study showed no disadvantages regarding HrQoL in PLWH after switching to DTG+DRV/r. Considering lifelong requirements for antiretroviral medication, close attention to HrQL is required.
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http://dx.doi.org/10.1080/09540121.2021.1916873DOI Listing
April 2021

Retracing the COVID-19 Pandemic in Germany from a Public Perspective using Google Search Queries Related to "coronavirus".

Gesundheitswesen 2021 May 16;83(5):e9-e14. Epub 2021 Apr 16.

Technical University of Munich, School of Medicine, Department of Dermatology and Allergy, Munich, Germany.

Aim Of The Study: During pandemics, the whole population is simultaneously confronted with the same health threat, resulting in enormous public interest. The current COVID-19 pandemic has left the world in a unique state of crisis. The aim of this analysis was to explore whether Google searches can be used to retrospectively retrace the COVID-19 pandemic in Germany and to detect local outbreaks by reflecting public interest in the virus.

Methods: Google Trends was used to explore the relative search volume (RSV) related to "coronavirus" from January 2020 to July 2020 in Germany. The RSV ranging between 0-100 was compared to new SARS-CoV-2 infections per day on a national level and to the cumulative infection numbers on a state level, as well as to important infectiological and political events.

Results: The most striking search peaks occurred after the first reported SARS-CoV-2 infection in Germany (January 27), during a major local outbreak in Heinsberg (February 25), after school closings (March 13) and the largest peak after nationwide contact restrictions (March 22) were announced. On a state level, peaks in RSV were observed after the first reported infection in each respective state. In addition, a higher RSV was recorded in states with higher numbers of infections (r=0,6, p=0,014) such as in Bavaria (RSV=96, 391 infections/100,000 inhabitants) and Baden-Württemberg (RSV=98, 340 infections/100,000 inhabitants). The lowest RSV (n=83) and lowest number of infections (50 infections/100,000 inhabitants) was observed in Mecklenburg-Western Pomerania. Since the end of May, SARS-CoV-2 related RSV remained at low level even when numbers of infections were temporarily rising due to local outbreaks such as the outbreak in Gütersloh, North Rhine-Westphalia.

Conclusion: RSV related to "coronavirus" precisely reflected public interest during the beginning of the COVID-19 pandemic. As public interest has strongly declined, information distribution regarding the newest developments over the entire course of the pandemic will be a major public health challenge.

Ziel Der Studie: Während Pandemien ist die gesamte Gesellschaft zur gleichen Zeit mit derselben Erkrankung konfrontiert, was zu großem öffentlichen Interesse führt. Die aktuelle COVID-19 Pandemie hat die ganze Welt in einen einmaligen Ausnahmezustand versetzt. Ziel dieser Studie war es zu untersuchen ob das Pandemiegeschehen in Deutschland anhand von Google Suchanfragen retrospektiv rekonstruiert werden kann und ob lokale Ausbrüche mithilfe von Google Daten detektiert werden können.

Methodik: Das relative Google Suchvolumen (RSV) zum Thema "Coronavirus" wurde für den Zeitraum von Januar bis Juli 2020 mit Google Trends analysiert. Das RSV, das zwischen 0 und 100 betragen kann, wurde auf Bundesebene mit den täglich neu gemeldeten SARS-CoV-2 Infektionszahlen und auf Länderebene mit den kumulativen Infektionszahlen pro Bundesland sowie wichtigen infektiologischen und politischen Ereignissen verglichen.

Ergebnisse: Höchstwerte im Google Suchvolumen nach der ersten gemeldeten SARS-CoV-2-Infektion in Deutschland (27. Januar), während des lokalen Ausbruchs in Heinsberg (25. Februar), nach den Schulschließungen (13. März) sowie, der absolute Höchstwert, nach Verkündung der bundesweiten Kontaktbeschränkungen (22. März) verzeichnet worden. Auf Bundesländerebene wurde immer dann ein Anstieg im Suchvolumen beobachtet, wenn die erste SARS-CoV-2 Infektion im jeweiligen Bundesland gemeldet wurde. Zudem wurde ein höheres RSV in Bundesländern mit mehr gemeldeten SARS-CoV-2-Infektionen registriert (r=0,6, p=0,014), wie z. B. in Bayern (RSV=96, 391 Infektionen/100 000 Einwohner) und Baden-Württemberg (RSV=98, 340 Infektionen/100 000 Einwohner). Das niedrigste RSV (n=83) und die niedrigste Anzahl an Infektionen (50 Infektionen/100 000 Einwohner) wurde in Mecklenburg-Vorpommern beobachtet. Seit Ende Mai ist das RSV bezüglich SARS-CoV-2 konstant gering, obwohl die Zahl an Neuinfektionen zwischenzeitlich aufgrund lokaler Ausbrüche gestiegen war wie z. B. der lokale Ausbruch in Gütersloh, Nordrhein-Westfalen. SCHLUßFOLGERUNG: Das RSV zum Thema "Coronavirus" bildeten das öffentliche Interesse während der ersten Monate der COVID-19 Pandemie präzise ab. Da das öffentliche Interesse jedoch stark nachgelassen hat, könnte es eine zentrale Herausforderung im weiteren Verlauf der Pandemie darstellen, die Bevölkerung weiterhin über neueste Entwicklungen und Maßnahmen informiert zu halten.
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http://dx.doi.org/10.1055/a-1398-5417DOI Listing
May 2021

An Eschar-like souvenir from a journey to Colombia: Ecthyma gangrenosum as a differential diagnosis of tropical diseases in immunocompromised patients - a case report.

BMC Infect Dis 2021 Apr 12;21(1):344. Epub 2021 Apr 12.

German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.

Background: Ecthyma gangrenosum (EG) is a cutaneous infectious disease characterized by eschar-like skin ulcers typically caused by Pseudomonas aeruginosa. Here, we report a case of relapsing EG in a patient who had returned from a trip to Colombia, thus establishing EG as an important differential diagnosis of tropical diseases, and demonstrating that even long-term antibiotic treatment can result in only partial remission of EG.

Case Presentation: A 77-year-old man with underlying chronic lymphocytic leukemia (CLL) on ibrutinib treatment was admitted because of a superinfected mosquito bite on the left ear and multiple partially necrotic skin lesions disseminated all over the entire body five days after returning from a trip to Colombia. The initial clinical suspicion of a tropical disease (leishmaniosis, systemic mycosis, or others) could not be confirmed. During the diagnostic workup, microbiological cultures of the skin biopsies and bronchoalveolar lavage revealed Pseudomonas aeruginosa, leading to a diagnosis of EG. Initial antibiotic treatment resulted in partial remission. However, the patient had to be re-admitted due to a relapse 3-4 weeks after the first episode. Finally, the patient was successfully treated with a combined approach consisting of antibiotics, recurrent surgical incisions, and administration of immunoglobulins.

Conclusions: In conclusion, EG should be considered as a differential diagnosis in immunosuppressed patients presenting with eschar-like skin ulcers. A combined treatment approach seems to be the best choice to achieve clinical cure and avoid relapse.
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http://dx.doi.org/10.1186/s12879-021-05998-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042936PMC
April 2021

Treatment of intestinal tuberculosis with small bowel perforation: a case report.

J Med Case Rep 2021 Mar 31;15(1):144. Epub 2021 Mar 31.

Department of Internal Medicine II, School of Medicine, University Hospital rechts der Isar, Technical University of Munich, Munich, Germany.

Background: Diagnosis of intestinal tuberculosis poses a dilemma to physicians due to nonspecific symptoms like abdominal pain, fever, nausea, and a change in bowel habit. In particular, the distinction between inflammatory bowel disease and intestinal tuberculosis remains challenging.

Case Presentation: A 27-year-old man from Colombia presented with fever, night sweats, and progressive lower abdominal pain. Computed tomography revealed a thickening of the bowel wall with a mesenterial lymphadenopathy, ascites ,and a pleural tumor mass. Histology of intestinal and pleural biopsy specimens showed a granulomatous inflammation. Although microscopy and polymerase chain reaction (PCR) for Mycobacterium tuberculosis (MTB) were negative, empirical MTB treatment was initiated on suspicion. Due to a massive post-stenotic atrophied intestinal bowel, MTB medications were administered parenterally in the initial phase of treatment to guarantee adequate systemic resorption. The complicated and critical further course included an intra-abdominal abscess and bowel perforation requiring a split stoma, before the patient could be discharged in good condition after 3 months of in-hospital care.

Conclusions: This case highlights the clinical complexity and diagnostic challenges of intestinal MTB infection. A multidisciplinary team of physicians should be sensitized to a timely diagnosis of this disease, which often mimics inflammation similar to inflammatory bowel disease, other infections, or malignancies. In our case, radiological findings, histological results, and migratory background underpinned the suspected diagnosis and allowed early initiation of tuberculostatic treatment.
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http://dx.doi.org/10.1186/s13256-021-02752-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011140PMC
March 2021

Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality.

medRxiv 2021 Mar 12. Epub 2021 Mar 12.

Background: There is considerable variability in COVID-19 outcomes amongst younger adults-and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium.

Method: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors.

Findings: We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2-1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3-1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors.

Interpretation: The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality-and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management.

Funding: Funding was obtained by each of the participating cohorts individually.
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http://dx.doi.org/10.1101/2021.03.07.21252875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987046PMC
March 2021

Invasive pulmonary aspergillosis in critically ill patients with severe COVID-19 pneumonia: Results from the prospective AspCOVID-19 study.

PLoS One 2021 17;16(3):e0238825. Epub 2021 Mar 17.

Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.

Background: Superinfections, including invasive pulmonary aspergillosis (IPA), are well-known complications of critically ill patients with severe viral pneumonia. Aim of this study was to evaluate the incidence, risk factors and outcome of IPA in critically ill patients with severe COVID-19 pneumonia.

Methods: We prospectively screened 32 critically ill patients with severe COVID-19 pneumonia for a time period of 28 days using a standardized study protocol for oberservation of developement of COVID-19 associated invasive pulmonary aspergillosis (CAPA). We collected laboratory, microbiological, virological and clinical parameters at defined timepoints in combination with galactomannan-antigen-detection from nondirected bronchial lavage (NBL). We used logistic regression analyses to assess if COVID-19 was independently associated with IPA and compared it with matched controls.

Findings: CAPA was diagnosed at a median of 4 days after ICU admission in 11/32 (34%) of critically ill patients with severe COVID-19 pneumonia as compared to 8% in the control cohort. In the COVID-19 cohort, mean age, APACHE II score and ICU mortality were higher in patients with CAPA than in patients without CAPA (36% versus 9.5%; p<0.001). ICU stay (21 versus 17 days; p = 0.340) and days of mechanical ventilation (20 versus 15 days; p = 0.570) were not different between both groups. In regression analysis COVID-19 and APACHE II score were independently associated with IPA.

Interpretation: CAPA is highly prevalent and associated with a high mortality rate. COVID-19 is independently associated with invasive pulmonary aspergillosis. A standardized screening and diagnostic approach as presented in our study can help to identify affected patients at an early stage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238825PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968651PMC
March 2021

Mucosal-Associated Invariant T (MAIT) Cells Are Highly Activated and Functionally Impaired in COVID-19 Patients.

Viruses 2021 02 3;13(2). Epub 2021 Feb 3.

Department of Internal Medicine II, University Hospital Rechts der Isar, School of Medicine, Technical University of Munich (TUM), 81675 Munich, Germany.

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprises mild courses of disease as well as progression to severe disease, characterised by lung and other organ failure. The immune system is considered to play a crucial role for the pathogenesis of COVID-19, although especially the contribution of innate-like T cells remains poorly understood. Here, we analysed the phenotype and function of mucosal-associated invariant T (MAIT) cells, innate-like T cells with potent antimicrobial effector function, in patients with mild and severe COVID-19 by multicolour flow cytometry. Our data indicate that MAIT cells are highly activated in patients with COVID-19, irrespective of the course of disease, and express high levels of proinflammatory cytokines such as IL-17A and TNFα ex vivo. Of note, expression of the activation marker HLA-DR positively correlated with SAPS II score, a measure of disease severity. Upon MAIT cell-specific in vitro stimulation, MAIT cells however failed to upregulate expression of the cytokines IL-17A and TNFα, as well as cytolytic proteins, that is, granzyme B and perforin. Thus, our data point towards an altered cytokine expression profile alongside an impaired antibacterial and antiviral function of MAIT cells in COVID-19 and thereby contribute to the understanding of COVID-19 immunopathogenesis.
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http://dx.doi.org/10.3390/v13020241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913667PMC
February 2021

Clinical Practice Guideline: Recommendations on Inpatient Treatment of Patients with COVID-19.

Dtsch Arztebl Int 2021 01 11;118(Forthcoming). Epub 2021 Jan 11.

Background: Since identification of the first cases in December 2019, COVID-19, caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has spread across the world, giving rise to a global pandemic.

Methods: A literature search was carried out in PubMed, using search terms defined by the authors. Questions important for the management of patients with COVID-19 were identified and discussed, and recommendations or statements on these topics were formulated in a structured consensus process.

Results: Determination of the indication for the admission of COVID-19 patients to the hospital should involve consideration of age, comorbidities, respiratory rate, and oxygen saturation. Every patient admitted without a recent PCR test should be tested immediately. It is recommended that any COVID-19 patient with hypoxemia (SpO2 <90%) despite being given oxygen, dyspnea, or a high respiratory rate be admitted to intensive care. In the case of hypoxemic respiratory insufficiency, an attempt at treatment with high-flow oxygen or non-invasive ventilation is suggested, while patients with severe hypoxemia/high respiratory rate should undergo intubation and invasive ventilation. In the presence of additional risk factors (such as obesity, known thrombophilia, intensive care treatment, or elevated D-dimers), intensified prophylaxis against thromboembolism may be indicated. Treatment with dexamethasone decreases the mortality among patients with severe or critical COVID-19. The important personal protection measures are attention to hygiene and the correct wearing of personal protective equipment.

Conclusion: The principal treatment measures are maintenance of adequate oxygenation, pharmacological prevention of thrombosis, and, in severe cases, administration of dexamethasone.
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http://dx.doi.org/10.3238/arztebl.m2021.0110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119662PMC
January 2021

Week 96 subgroup analyses of the phase 3, randomized AMBER and EMERALD trials evaluating the efficacy and safety of the once daily darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) single-tablet regimen in antiretroviral treatment (ART)-naïve and -experienced, virologically-suppressed adults living with HIV-1.

HIV Res Clin Pract 2020 Dec 2;21(6):151-167. Epub 2021 Feb 2.

Janssen Research and Development LLC, Raritan, NJ, USA.

Background: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated in AMBER (treatment-naïve adults; NCT02431247) and EMERALD (treatment-experienced, virologically-suppressed adults; NCT02269917).

Objective: To describe a Week 96 pre-planned subgroup analysis of D/C/F/TAF arms by demographic characteristics (age ≤/>50 years, gender, black/non-black race), and baseline clinical characteristics (AMBER: viral load [VL], CD4 count, WHO clinical stage, HIV-1 subtype and antiretroviral resistance; EMERALD: prior virologic failure [VF], antiretroviral experience, screening boosted protease inhibitor [PI], and boosting agent).

Methods: Patients in D/C/F/TAF and control arms could continue on/switch to D/C/F/TAF in a single-arm, open-label extension phase after Week 48 until Week 96. Efficacy endpoints were percentage cumulative confirmed VL ≥50 copies/mL (virologic rebound; EMERALD), and VL <50 (virologic response), or ≥50 copies/mL (VF) (FDA snapshot; both trials).

Results: D/C/F/TAF demonstrated high Week 96 virologic responses (AMBER: 85% [308/362]; EMERALD: 91% [692/763]) and low VF rates (AMBER: 6% [20/362]; EMERALD: 1% [9/763]). In EMERALD, D/C/F/TAF showed low virologic rebound cumulative through Week 96 (3% [24/763]). Results were consistent across subgroups, including prior antiretroviral experience in EMERALD. No darunavir, primary PI, or tenofovir resistance-associated mutations were observed post-baseline. Study-drug-related serious adverse events (AEs) and AE-related discontinuations were <1% and 2%, respectively (both D/C/F/TAF arms), and similar across subgroups. eGFR and bone mineral density improved or were stable and lipids increased through Week 96 across demographic subgroups, with small changes in total-cholesterol/HDL-cholesterol ratio.

Conclusions: D/C/F/TAF was effective with a high barrier to resistance and bone/renal safety benefits, regardless of demographic or clinical characteristics for treatment-naïve and treatment-experienced, virologically-suppressed adults.
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http://dx.doi.org/10.1080/25787489.2020.1844520DOI Listing
December 2020

[Steroids in infection medicine].

Dtsch Med Wochenschr 2021 Feb 29;146(3):162-166. Epub 2021 Jan 29.

Universitätsklinikum Freiburg, Abteilung Infektiologie, Klinik für Innere Medizin II, Freiburg.

Corticosteroids have been found as useful adjunctive therapy in patients with various infections and hyperinflammation-associated disease. They are recommended in practice guidelines for patients with tuberculous and pneumococcal meningitis and patients with immune reconstitution syndrome associated with antiretroviral therapy. A new indication is severe COVID-19. Evidence from clinical trials is insufficient to allow the routine use of steroids among patients with septic shock, community-acquired pneumonia or tuberculous pericarditis.
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http://dx.doi.org/10.1055/a-1302-3530DOI Listing
February 2021

SARS-CoV-2 infection is associated with a pro-thrombotic platelet phenotype.

Cell Death Dis 2021 01 5;12(1):50. Epub 2021 Jan 5.

Department of Internal Medicine I, School of Medicine, University hospital rechts der Isar, Technical University of Munich, Munich, Germany.

Novel coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state, characterized by abnormal coagulation parameters and by increased incidence of cardiovascular complications. With this study, we aimed to investigate the activation state and the expression of transmembrane proteins in platelets of hospitalized COVID-19 patients. We investigated transmembrane proteins expression with a customized mass cytometry panel of 21 antibodies. Platelets of 8 hospitalized COVID-19 patients not requiring intensive care support and without pre-existing conditions were compared to platelets of healthy controls (11 donors) with and without in vitro stimulation with thrombin receptor-activating peptide (TRAP). Mass cytometry of non-stimulated platelets detected an increased surface expression of activation markers P-Selectin (0.67 vs. 1.87 median signal intensity for controls vs. patients, p = 0.0015) and LAMP-3 (CD63, 0.37 vs. 0.81, p = 0.0004), the GPIIb/IIIa complex (4.58 vs. 5.03, p < 0.0001) and other adhesion molecules involved in platelet activation and platelet-leukocyte interactions. Upon TRAP stimulation, mass cytometry detected a higher expression of P-selectin in COVID-19 samples compared to controls (p < 0.0001). However, we observed a significantly reduced capacity of COVID-19 platelets to increase the expression of activation markers LAMP-3 and P-Selectin upon stimulation with TRAP. We detected a hyperactivated phenotype in platelets during SARS-CoV-2 infection, consisting of highly expressed platelet activation markers, which might contribute to the hypercoagulopathy observed in COVID-19. In addition, several transmembrane proteins were more highly expressed compared to healthy controls. These findings support research projects investigating antithrombotic and antiplatelet treatment regimes in COVID-19 patients, and provide new insights on the phenotypical platelet expression during SARS-CoV-2 infection.
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http://dx.doi.org/10.1038/s41419-020-03333-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790351PMC
January 2021

Immune deficiency is a risk factor for severe COVID-19 in people living with HIV.

HIV Med 2021 05 27;22(5):372-378. Epub 2020 Dec 27.

Gestione Ambulatoriale Politerapie (GAP) Outpatient Clinic, ASST Fatebenefratelli, Sacco University Hospital, Milan, Italy.

Objectives: A prior T cell depletion induced by HIV infection may carry deleterious consequences in the current COVID-19 pandemic. Clinical data on patients co-infected with HIV and SARS-CoV-2 are still scarce.

Methods: This multicentre cohort study evaluated risk factors for morbidity and mortality of COVID-19 in people living with HIV (PLWH), infected with SARS-CoV-2 in three countries in different clinical settings. COVID-19 was clinically classified as to be mild-to-moderate or severe.

Results: Of 175 patients, 49 (28%) had severe COVID-19 and 7 (4%) patients died. Almost all patients were on antiretroviral therapy (ART) and in 94%, HIV RNA was below 50 copies/mL prior to COVID-19 diagnosis. In the univariate analysis, an age 50 years or older, a CD4+ T cell nadir of < 200/µl, current CD4+ T cells < 350/µl and the presence of at least one comorbidity were significantly associated with severity of COVID-19. No significant association was found for gender, ethnicity, obesity, a detectable HIV RNA, a prior AIDS-defining illness, or tenofovir (which was mainly given as alafenamide) or protease inhibitor use in the current ART. In a multivariate analysis, the only factor associated with risk for severe COVID-19 was a current CD4+ T cell count of < 350/µl (adjusted odds ratio 2.85, 95% confidence interval 1.26-6.44, p=0.01). The only factor associated with mortality was a low CD4 T cell nadir.

Conclusions: In PLWH, immune deficiency is a possible risk factor for severe COVID-19, even in the setting of virological suppression. There is no evidence for a protective effect of PIs or tenofovir alafenamide.
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http://dx.doi.org/10.1111/hiv.13037DOI Listing
May 2021

Clinical and Ophthalmological Characteristics of Ocular Syphilis in a Retrospective Tertiary Hospital Cohort.

Sex Transm Dis 2021 06;48(6):436-442

Department of Ophthalmology.

Background: Data on ocular syphilis (OS) and its clinical presentation are currently insufficient. This study aimed to investigate the characteristics of a cohort with a high OS incidence at a university hospital in Germany, focusing on the clinical presentation of OS.

Methods: This single-center cohort study retrospectively analyzed data on 90 patients with 109 episodes of syphilis between 2008 and 2018. Cases of OS were identified and additionally reevaluated through a study-specific secondary assessment by an ophthalmologist specializing in uveitis.

Results: Twenty-three patients (26%) were diagnosed with OS, 16 (70%) of whom were with binocular involvement. Uveitis, especially that of the posterior segment, showed a high prevalence. Lumbar puncture was performed in 20 OS patients (87%), of whom 17 (85% of those with lumbar puncture/74% in total) met the 2018 Centers for Disease Control and Prevention criteria for likely neurosyphilis. Five (22%) of 23 patients had HIV infection, of whom 2 did not receive antiretroviral therapy. The preferred syphilis treatment regimens were benzylpenicillin and ceftriaxone, which yielded favorable serological, clinical, and ophthalmological outcomes.

Conclusions: A high incidence of OS was identified, and physicians should be aware of uveitis as a manifestation of syphilis. Most patients presented with uveitis and syphilis in an early or late latent stage and showed central nervous system involvement.
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http://dx.doi.org/10.1097/OLQ.0000000000001329DOI Listing
June 2021

Rates of bacterial co-infections and antimicrobial use in COVID-19 patients: a retrospective cohort study in light of antibiotic stewardship.

Eur J Clin Microbiol Infect Dis 2021 Apr 2;40(4):859-869. Epub 2020 Nov 2.

Department of Internal Medicine II, Technical University of Munich, School of Medicine, Munich, Germany.

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.
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http://dx.doi.org/10.1007/s10096-020-04063-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605734PMC
April 2021

[Erratum to: ].

Notf Rett Med 2020 Oct 20. Epub 2020 Oct 20.

Fakultät für Medizin, Klinik und Poliklinik für Innere Medizin II (Infektiologie), Klinikum rechts der Isar, Technische Universität München, München, Deutschland.

[This corrects the article DOI: 10.1007/s10049-020-00759-8.].
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http://dx.doi.org/10.1007/s10049-020-00797-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574395PMC
October 2020

A diagnostic algorithm for detection of urinary tract infections in hospitalized patients with bacteriuria: The "Triple F" approach supported by Procalcitonin and paired blood and urine cultures.

PLoS One 2020 22;15(10):e0240981. Epub 2020 Oct 22.

Department of Internal Medicine II, School of Medicine, Technical University of Munich, Munich, Germany.

For acute medicine physicians, distinguishing between asymptomatic bacteriuria (ABU) and clinically relevant urinary tract infections (UTI) is challenging, resulting in overtreatment of ABU and under-recognition of urinary-source bacteraemia without genitourinary symptoms (USB). We conducted a retrospective analysis of ED encounters in a university hospital between October 2013 and September 2018 who met the following inclusion criteria: Suspected UTI with simultaneous collection of paired urinary cultures and blood cultures (PUB) and determination of Procalcitonin (PCT). We sought to develop a simple algorithm based on clinical signs and PCT for the management of suspected UTI. Individual patient presentations were retrospectively evaluated by a clinical "triple F" algorithm (F1 ="fever", F2 ="failure", F3 ="focus") supported by PCT and PUB. We identified 183 ED patients meeting the inclusion criteria. We introduced the term UTI with systemic involvement (SUTI) with three degrees of diagnostic certainty: bacteremic UTI (24.0%; 44/183), probable SUTI (14.2%; 26/183) and possible SUTI (27.9%; 51/183). In bacteremic UTI, half of patients (54.5%; 24/44) presented without genitourinary symptoms. Discordant bacteraemia was diagnosed in 16 patients (24.6% of all bacteremic patients). An alternative focus was identified in 67 patients, five patients presented with S. aureus bacteremia. 62 patients were diagnosed with possible UTI (n = 20) or ABU (n = 42). Using the proposed "triple F" algorithm, dichotomised PCT of < 0.25 pg/ml had a negative predictive value of 88.7% and 96.2% for bacteraemia und accordant bacteraemia respectively. The application of the algorithm to our cohort could have resulted in 33.3% reduction of BCs. Using the diagnostic categories "possible" or "probable" SUTI as a trigger for initiation of antimicrobial treatment would have reduced or streamlined antimicrobial use in 30.6% and 58.5% of cases, respectively. In conclusion, the "3F" algorithm supported by PCT and PUB is a promising diagnostic and antimicrobial stewardship tool.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240981PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580978PMC
December 2020

DGI recommendations for COVID-19 pharmacotherapy.

Infection 2021 04 19;49(2):369-370. Epub 2020 Oct 19.

Department of Internal Medicine II, School of Medicine, University Hospital Rechts der Isar, Technical University of Munich, Munich, Germany.

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http://dx.doi.org/10.1007/s15010-020-01519-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569361PMC
April 2021
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