The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation.

Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action is unknown, and many patients deteriorate or die despite timely treatment initiation. Here, we identify dexamethasone treatment-induced cellular and molecular changes associated with improved survival in COVID-19 patients. We observed a reversal of transcriptional hallmark signatures in monocytes associated with severe COVID-19 and the induction of a monocyte substate characterized by the expression of glucocorticoid-response genes. These molecular responses to dexamethasone were detected in circulating and pulmonary monocytes, and they were directly linked to survival. Monocyte single-cell RNA sequencing (scRNA-seq)-derived signatures were enriched in whole blood transcriptomes of patients with fatal outcome in two independent cohorts, highlighting the potential for identifying non-responders refractory to dexamethasone. Our findings link the effects of dexamethasone to specific immunomodulation and reversal of monocyte dysregulation, and they highlight the potential of single-cell omics for monitoring in vivo target engagement of immunomodulatory drugs and for patient stratification for precision medicine approaches.

Alpha-1-antitrypsin-deficiency is associated with lower cardiovascular risk: an approach based on federated learning.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory multisystemic disease caused by environmental exposures and/or genetic factors. Inherited alpha-1-antitrypsin deficiency (AATD) is one of the best recognized genetic factors increasing the risk for an early onset COPD with emphysema. The aim of this study was to gain a better understanding of the associations between comorbidities and specific biomarkers in COPD patients with and without AATD to enable future investigations aimed, for example, at identifying risk factors or improving care. METHODS: We focused on cardiovascular comorbidities, blood high sensitivity troponin (hs-troponin) and lipid profiles in COPD patients with and without AATD. We used clinical data from six German University Medical Centres of the MIRACUM (Medical Informatics Initiative in Research and Medicine) consortium. The codes for the international classification of diseases (ICD) were used for COPD as a main diagnosis and for comorbidities and blood laboratory data were obtained. Data analyses were based on the DataSHIELD framework. RESULTS: Out of 112,852 visits complete information was available for 43,057 COPD patients. According to our findings, 746 patients with AATD (1.73%) showed significantly lower total blood cholesterol levels and less cardiovascular comorbidities than non-AATD COPD patients. Moreover, after adjusting for the confounder factors, such as age, gender, and nicotine abuse, we confirmed that hs-troponin is a suitable predictor of overall mortality in COPD patients. The comorbidities associated with AATD in the current study differ from other studies, which may reflect geographic and population-based differences as well as the heterogeneous characteristics of AATD. CONCLUSION: The concept of MIRACUM is suitable for the analysis of a large healthcare database. This study provided evidence that COPD patients with AATD have a lower cardiovascular risk and revealed that hs-troponin is a predictor for hospital mortality in individuals with COPD.

RSV vaccination strategies for high-risk patients 2023: a collaborative position paper by leading German medical societies and organizations.

Respiratory syncytial virus (RSV) inflicts severe illness and courses of infections not only in neonates, infants, and young children, but also causes significant morbidity and mortality in older adults and in people with immunosuppression, hemato-oncologic disease, chronic lung disease, or cardiovascular disease. In June and August 2023, effective vaccines against RSV were approved for the first time by the European Medicines Agency (EMA) for the EU. The respective pivotal studies showed a very high efficacy of the vaccine in preventing severe RSV-associated respiratory infections. At this point, use of the respective vaccines is restricted to persons aged 60 years or older, according to the registration studies. We therefore recommend use of the vaccination in persons aged 60 years or older. In addition, we recommend use of the vaccination in adults of any age with severe pulmonary or cardiovascular pre-existing conditions, as well as in adults with significant immune compromise, after individual consultation with the treating physician. Cost coverage can be applied for individually with the responsible health insurance company.

Pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH) in the German CAPNETZ-Cohort.

OBJECTIVES: The objective of this study was to identify the pathogen spectrum of community acquired pneumonia in people living with HIV (PLWH), and to compare it with a matched HIV negative group in order to reassess therapeutic strategies for PLWH. METHODS: Seventy-three (n = 73) PLWH (median CD4 3-6 months before CAP: 515/µl; SD 309) with community acquired pneumonia (CAP) were matched with 218 HIV-negative CAP controls in a prospective study design. Pathogen identifications used blood culture, samples from the upper and lower respiratory tract (culture and multiplex PCR) and urinary pneumococcal and legionella antigen test. RESULTS: Although the vaccination rate among PLWH with CAP was significantly higher (pneumococcal vaccination: 27.4 vs. 8.3%, p < 0.001; influenza vaccination: 34.2 vs. 17.4%, p = 0.009), pneumococci were found most frequently as pathogen among both PLWH (n = 19/21.3%) and controls (n = 34/17.2%; p = 0.410), followed by Haemophilus influenzae (PLWH, n = 12/13.5%, vs. controls, n = 25 / 12.6%; p = 0.850). Staphylococcus aureus was found equally in 20.2 and 19.2% in PLWH and controls, but infection or colonization could not be distinguished. Mortality during 6-month follow-up was significantly higher for PLWH (5/73, or 6.8%) versus controls (3/218, or 1.4%), however with lower case numbers than previously reported. Typical HIV-associated pathogens such as Pneumocystis jirovecii were found only exceptionally. CONCLUSIONS: Our study underscores the persistent clinical burden of CAP for PLWH. From pathogen perspective, empirical antibiotic treatment for CAP in PLWH on antiretroviral therapy should cover pneumococci and Haemophilus influenzae and may be adopted from valid common recommendations.

Comparison of clinical outcomes in hospitalized patients with COVID-19 or non-COVID-19 community-acquired pneumonia in a prospective observational cohort study.

PURPOSE: Coronavirus disease 2019 (COVID-19) and non-COVID-19 community-acquired pneumonia (NC-CAP) often result in hospitalization with considerable risks of mortality, ICU treatment, and long-term morbidity. A comparative analysis of clinical outcomes in COVID-19 CAP (C-CAP) and NC-CAP may improve clinical management. METHODS: Using prospectively collected CAPNETZ study data (January 2017 to June 2021, 35 study centers), we conducted a comprehensive analysis of clinical outcomes including in-hospital death, ICU treatment, length of hospital stay (LOHS), 180-day survival, and post-discharge re-hospitalization rate. Logistic regression models were used to examine group differences between C-CAP and NC-CAP patients and associations with patient demography, recruitment period, comorbidity, and treatment. RESULTS: Among 1368 patients (C-CAP: n = 344; NC-CAP: n = 1024), C-CAP showed elevated adjusted probabilities for in-hospital death (aOR 4.48 [95% CI 2.38-8.53]) and ICU treatment (aOR 8.08 [95% CI 5.31-12.52]) compared to NC-CAP. C-CAP patients were at increased risk of LOHS over seven days (aOR 1.88 [95% CI 1.47-2.42]). Although ICU patients had similar in-hospital mortality risk, C-CAP was associated with length of ICU stay over seven days (aOR 3.59 [95% CI 1.65-8.38]). Recruitment period influenced outcomes in C-CAP but not in NC-CAP. During follow-up, C-CAP was linked to a reduced risk of re-hospitalization and mortality post-discharge (aOR 0.43 [95% CI 0.27-0.70]). CONCLUSION: Distinct clinical trajectories of C-CAP and NC-CAP underscore the need for adapted management to avoid acute and long-term morbidity and mortality amid the evolving landscape of CAP pathogens.

Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON).

PURPOSE: The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score. METHODS: The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L). RESULTS: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001). CONCLUSION: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities. TRAIL REGISTRATION NUMBER: The cohort is registered at www. CLINICALTRIALS: gov under NCT04768998.

Comorbidity defines asthmatic patients' risk of COVID-19 hospitalization: A global perspective.

BACKGROUND: The global epidemiology of asthma among patients with coronavirus disease 2019 (COVID-19) presents striking geographic differences, defining prevalence zones of high and low co-occurrence of asthma and COVID-19. OBJECTIVE: We aimed to compare asthma prevalence among hospitalized patients with COVID-19 in major global hubs across the world by applying common inclusion criteria and definitions. METHODS: We built a network of 6 academic hospitals in Stanford (Stanford University)/the United States; Frankfurt (Goethe University), Giessen (Justus Liebig University), and Marburg (Philipps University)/Germany; and Moscow (Clinical Hospital 52 in collaboration with Sechenov University)/Russia. We collected clinical and laboratory data for patients hospitalized due to COVID-19. RESULTS: Asthmatic individuals were overrepresented among hospitalized patients with COVID-19 in Stanford and underrepresented in Moscow and Germany as compared with their prevalence among adults in the local community. Asthma prevalence was similar among patients hospitalized in an intensive care unit and patients hospitalized in other than an intensive care unit, which implied that the risk for development of severe COVID-19 was not higher among asthmatic patients. The numbers of males and comorbidities were higher among patients with COVID-19 in the Stanford cohort, and the most frequent comorbidities among these patients with asthma were other chronic inflammatory airway disorders such as chronic obstructive pulmonary disease. CONCLUSION: The observed disparity in COVID-19-associated risk among asthmatic patients across countries and continents is connected to the varying prevalence of underlying comorbidities, particularly chronic obstructive pulmonary disease.

Pathogenetic mechanisms and therapeutic approaches of acute-to-chronic liver failure.

Liver cirrhosis is the end stage of all chronic liver diseases and contributes significantly to overall mortality of 2% globally. The age-standardized mortality from liver cirrhosis in Europe is between 10 and 20% and can be explained by not only the development of liver cancer but also the acute deterioration in the patient's overall condition. The development of complications including accumulation of fluid in the abdomen (ascites), bleeding in the gastrointestinal tract (variceal bleeding), bacterial infections, or a decrease in brain function (hepatic encephalopathy) define an acute decompensation that requires therapy and often leads to acute-on-chronic liver failure (ACLF) by different precipitating events. However, due to its complexity and organ-spanning nature, the pathogenesis of ACLF is poorly understood, and the common underlying mechanisms leading to the development of organ dysfunction or failure in ACLF are still elusive. Apart from general intensive care interventions, there are no specific therapy options for ACLF. Liver transplantation is often not possible in these patients due to contraindications and a lack of prioritization. In this review, we describe the framework of the ACLF-I project consortium funded by the Hessian Ministry of Higher Education, Research and the Arts (HMWK) based on existing findings and will provide answers to these open questions.

Pulmonary impairment independently determines mortality in critically ill patients with acute-on-chronic liver failure.

BACKGROUND & AIMS: In ACLF patients, an adequate risk stratification is essential, especially for liver transplant allocation, since ACLF is associated with high short-term mortality. The CLIF-C ACLF score is the best prognostic model to predict outcome in ACLF patients. While lung failure is generally regarded as signum malum in ICU care, this study aims to evaluate and quantify the role of pulmonary impairment on outcome in ACLF patients. METHODS: In this retrospective study, 498 patients with liver cirrhosis and admission to IMC/ICU were included. ACLF was defined according to EASL-CLIF criteria. Pulmonary impairment was classified into three groups: unimpaired ventilation, need for mechanical ventilation and defined pulmonary failure. These factors were analysed in different cohorts, including a propensity score-matched ACLF cohort. RESULTS: Mechanical ventilation and pulmonary failure were identified as independent risk factors for increased short-term mortality. In matched ACLF patients, the presence of pulmonary failure showed the highest 28-day mortality (83.7%), whereas mortality rates in ACLF with mechanical ventilation (67.3%) and ACLF without pulmonary impairment (38.8%) were considerably lower (p < .001). Especially in patients with pulmonary impairment, the CLIF-C ACLF score showed poor predictive accuracy. Adjusting the CLIF-C ACLF score for the grade of pulmonary impairment improved the prediction significantly. CONCLUSIONS: This study highlights that not only pulmonary failure but also mechanical ventilation is associated with worse prognosis in ACLF patients. The grade of pulmonary impairment should be considered in the risk assessment in ACLF patients. The new score may be useful in the selection of patients for liver transplantation.

The ratio of neutrophil-to-lymphocyte and platelet-to-lymphocyte and association with mortality in community-acquired pneumonia: a derivation-validation cohort study.

RATIONALE: The ratio of neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR) and platelet-to-lymphocyte (PLR) are biomarkers that have shown potential for predicting mortality in several diseases. For patients hospitalized with community-acquired pneumonia (CAP), the prognostic capabilities of these biomarkers are unknown. OBJECTIVE: Investigate whether NLR, MLR or PLR were associated with 90-day mortality in CAP. Further, investigate whether the prediction rule CURB-65 could be improved by adding these biomarkers. METHODS: A derivation-validation study using a Danish multicentre retrospective cohort as the derivation cohort (N = 831) and a European multicentre prospective cohort as the validation cohort (N = 2463). Associations between biomarkers and mortality were assessed using Cox proportional hazard models with adjustments for sex, CURB-65 and comorbidities. A cut-off value for biomarkers was determined using Youden's J Statistics. The performance of CURB-65 with added biomarkers was evaluated using receiver-operating characteristics. RESULTS: In both cohorts increasing NLR and PLR were associated with 90-day mortality. In the derivation cohort, the hazard ratios for NLR and PLR were 1.016 (95% confidence interval (CI) 1.001-1.032, P = 0.038) and 1.001 (95% CI 1.000-1.001, P = 0.035), respectively. Adding these biomarkers to CURB-65 did not improve its performance. CONCLUSIONS: NLR and PLR were associated with 90-day mortality in CAP, but did not improve CURB-65.

Evolution of treatment patterns and survival outcomes in patients with advanced non-small cell lung cancer treated at Frankfurt University Hospital in 2012-2018.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved outcomes for patients with advanced non-small cell lung cancer (NSCLC) versus chemotherapy in clinical trials. In Germany, ICIs have been used clinically since 2015 for patients with advanced/metastatic NSCLC without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) aberrations. As part of I-O Optimise, a multinational research program utilizing real-world data on thoracic malignancies, we describe real-world treatment patterns and survival following reimbursement of ICIs for advanced NSCLC in Germany. METHODS: This retrospective cohort study included patients with locally advanced/metastatic NSCLC without known EGFR/ALK aberrations who received a first line of therapy at Frankfurt University Hospital between January 2012 and December 2018, with follow-up to December 2019 or death, whichever occurred first. Using electronic medical records, treatment patterns and survival outcomes were described by histology (squamous cell [SQ]; non-squamous cell [NSQ]/other) and time period (pre- and post-ICI approval). RESULTS: Among eligible patients who started first-line treatment, 136 (pre-ICI) and 126 (post-ICI) had NSQ/other histology, and 32 (pre-ICI) and 38 (post-ICI) had SQ histology. Use of an ICI in the NSQ/other cohort increased from 5.9% (all second- or third-line) in the pre-ICI period to 57.1% (22.2% in first-line, including 13.5% as monotherapy and 8.7% combined with chemotherapy) in the post-ICI period. This was paralleled by a significant (P < 0.0001) prolongation of median (95% CI) OS from 9.4 (7.1-11.1) to 14.8 (12.7-20.5) months between the pre-ICI and post-ICI periods. A similar increase in the uptake of ICI was observed for the SQ cohort (from 3.1% pre-ICI [fourth-line] to 52.6% post-ICI [28.9% as first-line, including 15.8% as monotherapy and 13.2% combined with chemotherapy]); however, analysis of survival outcomes was limited by small group sizes. CONCLUSION: These real-world data complement clinical trial evidence on the effectiveness of ICIs in patients with advanced NSCLC and NSQ/other histology in Germany.

[Measures and Recommendations for Ensuring Adequate Inpatient Care Capacities for Pandemic Management within a Region: Results of a Hybrid Delphi Method]. / Maßnahmen und Empfehlungen für die Sicherstellung adäquater stationärer Versorgungskapazitäten für das Pandemiemanagement innerhalb einer Region ­ Ergebnisse eines hybriden Delphi-Verfahrens.

INTRODUCTION: Since the beginning of the pandemic in spring 2020, inpatient healthcare has been under enormous burden, which is reflected especially in overworked staff, imprecise bed planning and/or data transfer. According to the recommendation of the Science Council, university clinics should play a controlling role in regional healthcare and act in conjunction with surrounding hospitals and practices. METHODS: In September 2021, 31 representatives from 18 university hospitals were invited to a hybrid Delphi study with a total of 4 survey rounds to discuss criteria for effective inpatient care in a pandemic situation, which were extracted from previous expert interviews. Criteria that were classified as very important/relevant by≥75% of the participants in the first round of the survey (consensus definition) were then further summarized in 4 different small groups. In a third Delphi round, all participants came together again to discuss the results of the small group discussions. Subsequently, these were prioritized as Optional ("can"), Desirable ("should") or Necessary ("must") recommendations. RESULTS: Of the invited clinical experts, 21 (67.7%) participated in at least one Delphi round. In an online survey (1st Delphi round), 233 criteria were agreed upon and reduced to 84 criteria for future pandemic management in four thematic small group discussions (2nd Delphi round) and divided into the small groups as follows: "Crisis Management and Crisis Plans" (n=20), "Human Resources Management and Internal Communication" (n=16), "Regional Integration and External Communication" (n=24) and "Capacity Management and Case & Care" (n=24). In the following group discussion (3rd Delphi round), the criteria were further modified and agreed upon by the experts, so that in the end result, there were 23 essential requirements and recommendations for effective inpatient care in a pandemic situation. CONCLUSION: The results draw attention to key demands of clinical representatives, for example, comprehensive digitization, standardization of processes and better (supra) regional networking in order to be able to guarantee needs-based care even under pandemic conditions. The present consensus recommendations can serve as guidelines for future pandemic management in the inpatient care sector.

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 » 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: NCT02139163.

A scoping review of mHealth monitoring of pediatric bronchial asthma before and during COVID-19 pandemic.

Mobile (m) Health technology is well-suited for Remote Patient Monitoring (RPM) in a patient's habitual environment. In recent years there have been fast-paced developments in mHealth-enabled pediatric RPM, especially during the COVID-19 pandemic, necessitating evidence synthesis. To this end, we conducted a scoping review of clinical trials that had utilized mHealth-enabled RPM of pediatric asthma. MEDLINE, Embase and Web of Science were searched from September 1, 2016 through August 31, 2021. Our scoping review identified 25 publications that utilized synchronous and asynchronous mHealth-enabled RPM in pediatric asthma, either involving mobile applications or via individual devices. The last three years has seen the development of evidence-based, multidisciplinary, and participatory mHealth interventions. The quality of the studies has been improving, such that 40% of included study reports were randomized controlled trials. In conclusion, there exists high-quality evidence on mHealth-enabled RPM in pediatric asthma, warranting future systematic reviews and/or meta-analyses of the benefits of such RPM.

[Patients with lung disease caused by non-tuberculous mycobacteria in Germany: a trans-sectoral patient-oriented care concept]. / Versorgung von Patienten/innen mit einer durch nichttuberkulöse Mykobakterien verursachten Lungenerkrankung in Deutschland ­ ein transsektorales patientenorientiertes Versorgungskonzept.

INTRODUCTION: Management of patients with lung disease caused by non-tuberculous mycobacteria (NTM-LD) in Germany is currently characterized by delayed diagnosis, frequently poor prognosis and high follow-up costs. Mainly due to an increased number of hospitalizations, the SHI-relevant direct costs (€ 9,093.20 patient/year) are higher compared to typical underlying diseases (e.g. asthma: € 706.00 patient/year). This less than optimal NTM care is mainly caused by lack of awareness of the disease at primary care and out-patient specialist care level, largely absent structured referral structures and limited communication between specialists out of hospital with specialized NTM clinics. Lack of incentives to support these communication pathways is part of the problem. Sufficient, appropriate and economically sustainable care is hampered by poor adherence to treatment recommendations. METHODS: For the development of the NTM care concept, relevant professional societies and patient organizations were interviewed about the care situation. Thereafter, 20 NTM-LD patients, 5 residential pulmonologists and 8 experts were interviewed in an explorative qualitative interview to determine the current patient pathway. Based on the findings, the NTM care concept was developed in an advisory board by the authors. RESULTS: Regional management centers should concentrate specific expertise and ensure quality of care through routine consultation and involvement in diagnosis, decision-making on treatment necessity, initiation of therapy, follow-up examinations, and determination of the therapy success, as well as adequate follow-up of patients. The referring pulmonologist should continue to provide case-specific therapy support close to the patient's home in preferred shared-care concept. The establishment of clear referral structures and case identification criteria will help residential physicians to include patients at risk in the NTM-care system early. Patients and pulmonologists without specific expertise need to be made aware of the care pathway and severity of NTM-LD. CONCLUSION: The increased morbidity and mortality of NTM-LD patients must be addressed with patient-oriented, interdisciplinary and trans-sectoral care concept. An NTM care system with clear treatment procedures and referral structures is proposed for a nationwide pilot project.

Analysis of Humoral Immune Responses in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a pandemic with tens of millions of cases and hundreds of thousands of deaths. The infection causes coronavirus disease 2019 (COVID-19), a disease of the respiratory system of divergent severity. In the current study, humoral immune responses were characterized in a cohort of 143 patients with COVID-19 from the University Hospital Frankfurt am Main, Germany. METHODS: SARS-CoV-2-specific-antibodies were detected by enzyme-linked immunosorbent assay (ELISA). SARS-CoV-2 and human coronavirus NL63 neutralization activity was analyzed with pseudotyped lentiviral vectors. RESULTS: The severity of COVID-19 increased with age, and male patients encountered more serious symptoms than female patients. Disease severity was correlated with the amount of SARS-CoV-2-specific immunoglobulin (Ig) G and IgA and the neutralization activity of the antibodies. The amount of SARS-CoV-2-specific IgG antibodies decreased with time after polymerase chain reaction conformation of the infection, and antibodies directed against the nucleoprotein waned faster than spike protein-directed antibodies. In contrast, for the common flu coronavirus NL63, COVID-19 disease severity seemed to be correlated with low NL63-neutralizing activities, suggesting the possibility of cross-reactive protection. CONCLUSION: The results describe the humoral immune responses against SARS-CoV-2 and might aid the identification of correlates of protection needed for vaccine development.

Evaluation of a multiplex PCR screening approach to identify community-acquired bacterial co-infections in COVID-19: a multicenter prospective cohort study of the German competence network of community-acquired pneumonia (CAPNETZ).

PURPOSE: Thorough knowledge of the nature and frequency of co-infections is essential to optimize treatment strategies and risk assessment in cases of coronavirus disease 2019 (COVID-19). This study aimed to evaluate the multiplex polymerase chain reaction (PCR) screening approach for community-acquired bacterial pathogens (CABPs) at hospital admission, which could facilitate identification of bacterial co-infections in hospitalized COVID-19 patients. METHODS: Clinical data and biomaterials from 200 hospitalized COVID-19 patients from the observational cohort of the Competence Network for community-acquired pneumonia (CAPNETZ) prospectively recruited between March 17, 2020, and March 12, 2021 in 12 centers in Germany and Switzerland, were included in this study. Nasopharyngeal swab samples were analyzed on hospital admission using multiplex real-time reverse transcription (RT)-PCR for a broad range of CABPs. RESULTS: In total of 200 patients Staphylococcus aureus (27.0%), Haemophilus influenzae (13.5%), Streptococcus pneumoniae (5.5%), Moraxella catarrhalis (2.5%), and Legionella pneumophila (1.5%) were the most frequently detected bacterial pathogens. PCR detection of bacterial pathogens correlated with purulent sputum, and showed no correlation with ICU admission, mortality, and inflammation markers. Although patients who received antimicrobial treatment were more often admitted to the ICU and had a higher mortality rate, PCR pathogen detection was not significantly related to antimicrobial treatment. CONCLUSION: General CABP screening using multiplex PCR with nasopharyngeal swabs may not facilitate prediction or identification of bacterial co-infections in the early phase of COVID-19-related hospitalization. Most patients with positive PCR results appear to be colonized rather than infected at that time, questioning the value of routine antibiotic treatment on admission in COVID-19 patients.

Technical Innovations in Pneumology: E-Health, Screening, Diagnostics, and Therapy.

At the 2020 "Luftschlösser" (castles in the air) conference, experts from a wide range of pneumological fields discussed technical innovations in pneumology, which can be seen in many different areas of the field, including e-health, screening, diagnostics, and therapy. They contribute to substantial advancements ranging from the innovative use of diagnostic tools to novel treatments for chronic lung diseases. Artificial intelligence enables broader screening, which can be expected to have beneficial effects on disease progression and overall prognosis. There is still a high demand for clinical trials to investigate the usefulness and risk-benefit ratio. Open questions remain especially about the quality and utility of medical apps in an inadequately regulated market. This article weighs the pros and cons of technical innovations in specific subspecialties of pneumology based on the lively exchange of ideas among various pneumological experts.

No SARS-CoV-2 detection in the German CAPNETZ cohort of community acquired pneumonia before COVID-19 peak in March 2020.

PURPOSE: The first SARS-CoV-2 cases in Europe were reported in January 2020. Recently, concern arose on unrecognized infections before this date. For a better understanding of the pandemic, we retrospectively analyzed patient samples for SARS-CoV-2 from the prospective CAPNETZ study cohort. METHODS: We used nasopharyngeal swab samples from a cohort of well characterized patients with community acquired pneumonia of the CAPNETZ study group, recruited from different geographic regions across Germany, Austria, the Netherlands, and Switzerland between 02nd December 2019 and 28th April 2020. Multiplex real-time RT-PCR for a broad range of respiratory pathogens and SARS-CoV-2 real-time RT-PCR were performed on all samples. RESULTS: In our cohort, respiratory pathogens other than SARS-CoV-2 were detected in 21.5% (42/195) of patients with rhinovirus as the most frequently detected pathogen. The detection rate increased to 29.7% (58/195) when SARS-CoV-2 was included. No SARS-CoV-2 positive sample was detected before end of March 2020. CONCLUSIONS: Respiratory viral pathogens accounted for a considerable number of positive results but no SARS-CoV-2 case was identified before the end of March 2020.