Unmet needs in pneumonia research: a comprehensive approach by the CAPNETZ study group

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

Early post‑discharge mortality in CAP: frequency, risk factors and a prediction tool

There are few data on mortality after discharge with community-acquired pneumonia (CAP). Therefore, we evaluated risk factors for 30-day post-discharge mortality after CAP. We included all patients of the prospective multi-national CAPNETZ study between 2002 and 2018 with (1) hospitalized CAP, (2) survival until discharge, and (3) complete follow-up data. The study endpoint was death within 30 days after discharge. We evaluated risk factors including demographics, comorbidities, admission CAP severity, and laboratory values and treatment-related factors in uni- and multivariable analyses. A total of 126 (1.6%) of 7882 included patients died until day 30 after discharge, corresponding to 26% of all 476 deaths. After multivariable analysis, we identified 10 independent risk factors: higher age, lower BMI, presence of diabetes mellitus, chronic renal or chronic neurological disease (other than cerebrovascular diseases), low body temperature or higher thrombocytes on admission, extended length of hospitalization, oxygen therapy during hospitalization, and post-obstructive pneumonia. By addition these factors, we calculated a risk score with an AUC of 0.831 (95%CI 0.822–0.839, p < 0.001) for prediction of post-discharge mortality. Early post-discharge deaths account for ¼ of all CAP-associated deaths and are associated with patient- and CAP-severity-related risk factors. Additional studies are necessary to replicate our findings in independent cohorts. Study registration: NCT 02139163

A longitudinal analysis of pneumococcal vaccine serotypes in pneumonia patients in Germany

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

A longitudinal analysis of pneumococcal vaccine serotypes in pneumonia patients in Germany

In Germany, the recently approved 20-valent pneumococcal conjugate vaccine had a substantially higher coverage against pneumonia in adults than the 13-valent vaccine, while the coverage gap compared to the 23-valent polysaccharide vaccine was small https://bit.ly/3q4sko

PedCAPNETZ – prospective observational study on community acquired pneumonia in children and adolescents

Background: Pediatric community acquired pneumonia (pedCAP) is one of the leading causes for childhood morbidity accounting for up to 20% of pediatric hospital admissions in high income countries. In spite of its high morbidity, updated epidemiological and pathogen data after introduction of preventive vaccination and novel pathogen screening strategies are limited. Moreover, there is a need for validated recommendations on diagnostic and treatment regimens in pedCAP. Through collection of patient data and analysis of pathogen and host factors in a large sample of unselected pedCAP patients in Germany, we aim to address and substantially improve this situation. Methods: pedCAPNETZ is an observational, multi-center study on pedCAP. Thus far, nine study centers in hospitals, outpatient clinics and practices have been initiated and more than 400 patients with radiologically confirmed pneumonia have been enrolled, aiming at a total of 1000 study participants. Employing an online data base, information on disease course, treatment as well as demographical and socioeconomical data is recorded. Patients are followed up until day 90 after enrollment; Comprehensive biosample collection and a central pedCAPNETZ biobank allow for in-depth analyses of pathogen and host factors. Standardized workflows to assure sample logistics and data management in more than fifteen future study centers have been established. Discussion: Through comprehensive epidemiological, clinical and biological analyses, pedCAPNETZ fills an important gap in pediatric and infection research. To secure dissemination of the registry, we will raise clinical and scientific awareness at all levels. We aim at participating in decision making processes for guidelines and prevention strategies. Ultimately, we hope the results of the pedCAPNETZ registry will help to improve care and quality of life in pedCAP patients in the future

Pathogen spectra in hospitalised and nonhospitalised children with community-acquired pneumonia

Background Paediatric community-acquired pneumonia (CAP) is a leading cause of paediatric morbidity. However, particularly for outpatients with paediatric CAP, data on aetiology and management are scarce. Methods The prospective pedCAPNETZ study multicentrically enrols children and adolescents with outpatient-treated or hospitalised paediatric CAP in Germany. Blood and respiratory specimens were collected systematically, and comprehensive analyses of pathogen spectra were conducted. Follow-up evaluations were performed until day 90 after enrolment. Results Between December 2014 and August 2020, we enrolled 486 children with paediatric CAP at eight study sites, 437 (89.9%) of whom had radiographic evidence of paediatric CAP. Median (interquartile range) age was 4.5 (1.6–6.6) years, and 345 (78.9%) children were hospitalised. The most prevalent symptoms at enrolment were cough (91.8%), fever (89.2%) and tachypnoea (62.0%). Outpatients were significantly older, displayed significantly lower C-reactive protein levels and were significantly more likely to be symptom-free at follow-up days 14 and 90. Pathogens were detected in 90.3% of all patients (one or more viral pathogens in 68.1%; one or more bacterial strains in 18.7%; combined bacterial/viral pathogens in 4.1%). Parainfluenza virus and Mycoplasma pneumoniae were significantly more frequent in outpatients. The proportion of patients with antibiotic therapy was comparably high in both groups (92.4% of outpatients versus 86.2% of hospitalised patients). Conclusion We present first data on paediatric CAP with comprehensive analyses in outpatients and hospitalised cases and demonstrate high detection rates of viral pathogens in both groups. Particularly in young paediatric CAP patients with outpatient care, antibiotic therapy needs to be critically debated

Psychometric Validation of the German Translation of the Quality of Life Questionnaire-Bronchiectasis (QOL-B)&mdash;Data from the German Bronchiectasis Registry PROGNOSIS

Patients with bronchiectasis feature considerable symptom burden and reduced health-related quality of life (QOL). We provide the psychometric validation of the German translation of the disease-specific Quality of Life Questionnaire-Bronchiectasis (QOL-B), version 3.1, using baseline data of adults consecutively enrolled into the prospective German bronchiectasis registry PROGNOSIS. Overall, 904 patients with evaluable QOL-B scores were included. We observed no relevant floor or ceiling effects. Internal consistency was good to excellent (Cronbach&rsquo;s &alpha; &ge;0.73 for each scale). QOL-B scales discriminated between patients based on prior pulmonary exacerbations and hospitalizations, breathlessness, bronchiectasis severity index, lung function, sputum volume, Pseudomonas aeruginosa status and the need for regular pharmacotherapy, except for Social Functioning, Vitality and Emotional Functioning scales. We observed moderate to strong convergence between several measures of disease severity and QOL-B scales, except for Social and Emotional Functioning. Two-week test-retest reliability was good, with intraclass correlation coefficients &ge;0.84 for each scale. Minimal clinical important difference ranged between 8.5 for the Respiratory Symptoms and 14.1 points for the Social Functioning scale. Overall, the German translation of the QOL-B, version 3.1, has good validity and test-retest reliability among a nationally representative adult bronchiectasis cohort. However, responsiveness of QOL-B scales require further investigation during registry follow-up