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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.
Background: Peritonitis is responsible for thousands of deaths annually in Germany alone. Even source control (SC) and antibiotic treatment often fail to prevent severe sepsis or septic shock, and this situation has hardly improved in the past two decades. Most experimental immunomodulatory therapeutics for sepsis have been aimed at blocking or dampening a specific pro-inflammatory immunological mediator. However, the patient collective is large and heterogeneous. There are therefore grounds for investigating the possibility of developing personalized therapies by classifying patients into groups according to biomarkers. This study aims to combine an assessment of the efficacy of treatment with a preparation of human immunoglobulins G, A, and M (IgGAM) with individual status of various biomarkers (immunoglobulin level, procalcitonin, interleukin 6, antigen D-related human leucocyte antigen (HLA-DR), transcription factor NF-κB1, adrenomedullin, and pathogen spectrum).
Methods/design: A total of 200 patients with sepsis or septic shock will receive standard-of-care treatment (SoC). Of these, 133 patients (selected by 1:2 randomization) will in addition receive infusions of IgGAM for 5 days. All patients will be followed for approximately 90 days and assessed by the multiple-organ failure (MOF) score, by the EQ QLQ 5D quality-of-life scale, and by measurement of vital signs, biomarkers (as above), and survival.
Discussion: This study is intended to provide further information on the efficacy and safety of treatment with IgGAM and to offer the possibility of correlating these with the biomarkers to be studied. Specifically, it will test (at a descriptive level) the hypothesis that patients receiving IgGAM who have higher inflammation status (IL-6) and poorer immune status (low HLA-DR, low immunoglobulin levels) have a better outcome than patients who do not receive IgGAM. It is expected to provide information that will help to close the knowledge gap concerning the association between the effect of IgGAM and the presence of various biomarkers, thus possibly opening the way to a personalized medicine.
Trial registration: EudraCT, 2016–001788-34; ClinicalTrials.gov, NCT03334006. Registered on 17 Nov 2017.
Trial sponsor: RWTH Aachen University, represented by the Center for Translational & Clinical Research Aachen (contact Dr. S. Isfort).
To assess the scope of infection control measures for multidrug-resistant bacteria in high-risk settings, a survey among university hospitals was conducted. Fourteen professionals from 8 sites participated. Reported policies varied largely with respect to the types of wards conducting screening, sample types used for screening and implementation of contact precautions. This variability among sites highlights the need for an evidence-based consensus of current infection control policies.
Background: Pulmonary nocardiosis (PN) is an uncommon but potentially life-threatening infection. Most of our knowledge is derived from case reports or smaller case series. Recently, increasing PN incidence rates have been reported. We aim to describe the clinical course of and risk factors for PN in four Western European countries and to estimate population-based annual hospitalization rates.
Methods: Retrospective evaluation (1995 to 2011) of the clinical course of and risk factors for PN in patients from 11 hospitals in four European countries (Germany, Austria, Switzerland and The Netherlands). Calculation of population-based estimates of hospitalization rates of PN in Germany (2005 to 2011) using official German nationwide diagnosis-related groups (DRG) hospital statistics.
Results: Forty-three patients fulfilled stringent criteria for proven (n = 8) and probable (n = 35) PN; seven with extrapulmonary dissemination. Within the 43 patients, major PN risk factors were immunocompromising (83.7%) and/or pulmonary (58.1%; in 27.9% as only comorbidity) comorbidities. Median duration of PN targeted therapy was 12 weeks. Distinguished patterns of resistance were observed (imipenem susceptibility: N. farcinica 33.3%; N. asteroides 66.7%). Overall mortality rate was 18.9%; in disseminated PN 50%. Over time, annual PN hospitalization rates remained unchanged at around 0.04/100′000 with the highest rate among men aged 75–84 years (0.24/100′000).
Conclusion: PN is rare, but potentially life-threatening, and mainly affects immunocompromised elder males. Overall annual hospitalization rates remained stable between 2005 and 2011.
Recently, a 15-valent (PCV15) and a 20-valent pneumococcal conjugate vaccine (PCV20) have been licensed by the US Food and Drug Administration and are under evaluation by the European Medicines Agency. PCV15 contains all serotypes of the 13-valent conjugate vaccine (PCV13) plus serotype 22F and 33F and PCV20 includes PCV13 serotypes plus serotypes 8, 10A, 11A, 12F, 15B, 22F, 33F. We investigated pneumococcal serotype distribution, secular trends and proportion of pneumonia caused by serotypes included in PCV13, PCV15, PCV20, and the 23-valent pneumococcal polysaccharide vaccine (PPV23) among adult patients with all-cause community-acquired pneumonia (CAP) between 2013 and 2019. We applied logistic mixed regression modelling to assess annual trends. Urine samples from adult patients with CAP treated in the community or hospital in Germany and included in the CAPNETZ study, a prospective multi-centre cohort study, were analysed by two serotype-specific multiplex urinary antigen detection assays (UAD1/UAD2) at Pfizer’s Vaccines Research and Development Laboratory. UAD1 detects serotypes in PCV13, UAD2 detects additional serotypes in PCV20 plus serotypes 2, 9N, 17F and 20. Out of 1,831 patients screened, urine samples with a valid UAD test result were available for 1,343 patients (73.3%). Among those patients, 829 patients (61.7%) were male, 792 patients (59.0%) were aged ≥60 years, 1038 patients (77.3%) had at least one comorbidity and 1,204 patients (89.7%) were treated in the hospital. The overall proportion of vaccine-type pneumonia among all-cause CAP for PCV13, PCV15, PCV20 and PPV23 was 7.7% (n=103), 9.1% (n=122), 12.3% (n=165) and 13.3% (n=178). Over the entire observation period, we did not observe evidence for significant annual trends in pneumococcal vaccine serotype coverage against pneumonia in adults (PCV13: OR 0.94, 95% CI 0.83-1.05; PCV15: OR 0.93, 95% CI 0.84-1.03; PCV20: OR 0.95, 95% CI 0.86-1.04; PPV23: OR 0.99, 95% CI 0.90-1.08). In conclusion, our data show that i) the infant vaccination program of PCV13, which started in Germany 2010 did not result in a relevant and sustained decrease of PCV13 serotypes in pneumonia in adults and ii) that the gap in the coverage between PCV20 and PPV23 was small and did not increase over the entire observation time.
Introduction: Despite improvements in medical science and public health, mortality of community-acquired pneumonia (CAP) has barely changed throughout the last 15 years. The current SARS-CoV-2 pandemic has once again highlighted the central importance of acute respiratory infections to human health. The “network of excellence on Community Acquired Pneumonia” (CAPNETZ) hosts the most comprehensive CAP database worldwide including more than 12,000 patients. CAPNETZ connects physicians, microbiologists, virologists, epidemiologists, and computer scientists throughout Europe. Our aim was to summarize the current situation in CAP research and identify the most pressing unmet needs in CAP research.
Methods: To identify areas of future CAP research, CAPNETZ followed a multiple-step procedure. First, research members of CAPNETZ were individually asked to identify unmet needs. Second, the top 100 experts in the field of CAP research were asked for their insights about the unmet needs in CAP (Delphi approach). Third, internal and external experts discussed unmet needs in CAP at a scientific retreat.
Results: Eleven topics for future CAP research were identified: detection of causative pathogens, next generation sequencing for antimicrobial treatment guidance, imaging diagnostics, biomarkers, risk stratification, antiviral and antibiotic treatment, adjunctive therapy, vaccines and prevention, systemic and local immune response, comorbidities, and long-term cardio-vascular complications.
Conclusion: Pneumonia is a complex disease where the interplay between pathogens, immune system and comorbidities not only impose an immediate risk of mortality but also affect the patients’ risk of developing comorbidities as well as mortality for up to a decade after pneumonia has resolved. Our review of unmet needs in CAP research has shown that there are still major shortcomings in our knowledge of CAP.
Recently, a 15-valent (PCV15) and a 20-valent pneumococcal conjugate vaccine (PCV20) have been licensed by the US Food and Drug Administration and are under evaluation by the European Medicines Agency. PCV15 contains all serotypes of the 13-valent conjugate vaccine (PCV13) plus serotype 22F and 33F and PCV20 includes PCV13 serotypes plus serotypes 8, 10A, 11A, 12F, 15B, 22F, 33F. We investigated pneumococcal serotype distribution, secular trends and proportion of pneumonia caused by serotypes included in PCV13, PCV15, PCV20, and the 23-valent pneumococcal polysaccharide vaccine (PPV23) among adult patients with all-cause community-acquired pneumonia (CAP) between 2013 and 2019. We applied logistic mixed regression modelling to assess annual trends. Urine samples from adult patients with CAP treated in the community or hospital in Germany and included in the CAPNETZ study, a prospective multi-centre cohort study, were analysed by two serotype-specific multiplex urinary antigen detection assays (UAD1/UAD2) at Pfizer’s Vaccines Research and Development Laboratory. UAD1 detects serotypes in PCV13, UAD2 detects additional serotypes in PCV20 plus serotypes 2, 9N, 17F and 20. Out of 1,831 patients screened, urine samples with a valid UAD test result were available for 1,343 patients (73.3%). Among those patients, 829 patients (61.7%) were male, 792 patients (59.0%) were aged ≥60 years, 1038 patients (77.3%) had at least one comorbidity and 1,204 patients (89.7%) were treated in the hospital. The overall proportion of vaccine-type pneumonia among all-cause CAP for PCV13, PCV15, PCV20 and PPV23 was 7.7% (n=103), 9.1% (n=122), 12.3% (n=165) and 13.3% (n=178). Over the entire observation period, we did not observe evidence for significant annual trends in pneumococcal vaccine serotype coverage against pneumonia in adults (PCV13: OR 0.94, 95% CI 0.83-1.05; PCV15: OR 0.93, 95% CI 0.84-1.03; PCV20: OR 0.95, 95% CI 0.86-1.04; PPV23: OR 0.99, 95% CI 0.90-1.08). In conclusion, our data show i) no decline of PCV13 serotypes in all-cause CAP between 2013-2019 mainly due to a persistently high proportion of serotype 3 suggesting no meaningful effect of childhood PCV13 vaccination on PCV13 coverage in pneumonia in adults during this time period and ii) that the gap in the coverage between PCV20 and PPV23 was small and did not increase over the entire observation time.
We show a shift in the prevalence of respiratory viral pathogens in community-acquired pneumonia patients during the COVID-19 pandemic. Our data support the efficiency of non-pharmaceutical interventions on virus circulation except for rhinoviruses. The consequences of an altered circulation on subsequent winter seasons remain unclear and support the importance of systematic virological surveillance.