Antibody evasion properties of SARS-CoV-2 Omicron sublineages.

The identification of the Omicron (B.1.1.529.1 or BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Botswana in November 20211 immediately caused concern owing to the number of alterations in the spike glycoprotein that could lead to antibody evasion. We2 and others3-6 recently reported results confirming such a concern. Continuing surveillance of the evolution of Omicron has since revealed the rise in prevalence of two sublineages, BA.1 with an R346K alteration (BA.1+R346K, also known as BA.1.1) and B.1.1.529.2 (BA.2), with the latter containing 8 unique spike alterations and lacking 13 spike alterations found in BA.1. Here we extended our studies to include antigenic characterization of these new sublineages. Polyclonal sera from patients infected by wild-type SARS-CoV-2 or recipients of current mRNA vaccines showed a substantial loss in neutralizing activity against both BA.1+R346K and BA.2, with drops comparable to that already reported for BA.1 (refs. 2,3,5,6). These findings indicate that these three sublineages of Omicron are antigenically equidistant from the wild-type SARS-CoV-2 and thus similarly threaten the efficacies of current vaccines. BA.2 also exhibited marked resistance to 17 of 19 neutralizing monoclonal antibodies tested, including S309 (sotrovimab)7, which had retained appreciable activity against BA.1 and BA.1+R346K (refs. 2-4,6). This finding shows that no authorized monoclonal antibody therapy could adequately cover all sublineages of the Omicron variant, except for the recently authorized LY-CoV1404 (bebtelovimab).

Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2.

The B.1.1.529/Omicron variant of SARS-CoV-2 was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally1. It is expected to become dominant in the coming weeks2, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations3 that pose a threat to the efficacy of current COVID-19 vaccines and antibody therapies4. This concern is amplified by the findings of our study. Here we found that B.1.1.529 is markedly resistant to neutralization by serum not only from patients who recovered from COVID-19, but also from individuals who were vaccinated with one of the four widely used COVID-19 vaccines. Even serum from individuals who were vaccinated and received a booster dose of mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies against all known epitope clusters on the spike protein, we noted that the activity of 17 out of the 19 antibodies tested were either abolished or impaired, including ones that are currently authorized or approved for use in patients. Moreover, we also identified four new spike mutations (S371L, N440K, G446S and Q493R) that confer greater antibody resistance on B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.

[Guideline for the Diagnosis and Treatment of Asthma - Addendum 2020 - Guideline of the German Respiratory Society and the German Atemwegsliga in Cooperation with the Paediatric Respiratory Society and the Austrian Society of Pneumology]. / S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma ­ Addendum 2020.

The present addendum of the guideline for the diagnosis and treatment of asthma (2017) complements new insights into the diagnosis and management of asthma as well as for the newly approved drugs for the treatment of asthma. Current, evidence-based recommendations on diagnostic and therapeutic approaches are presented for children and adolescents as well as for adults with asthma.

Discovery of the FDA-approved drugs bexarotene, cetilistat, diiodohydroxyquinoline, and abiraterone as potential COVID-19 treatments with a robust two-tier screening system.

Coronavirus Disease 2019 (COVID-19) caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a crude case fatality rate of about 0.5-10 % depending on locality. A few clinically approved drugs, such as remdesivir, chloroquine, hydroxychloroquine, nafamostat, camostat, and ivermectin, exhibited anti-SARS-CoV-2 activity in vitro and/or in a small number of patients. However, their clinical use may be limited by anti-SARS-CoV-2 50 % maximal effective concentrations (EC50) that exceeded their achievable peak serum concentrations (Cmax), side effects, and/or availability. To find more immediately available COVID-19 antivirals, we established a two-tier drug screening system that combines SARS-CoV-2 enzyme-linked immunosorbent assay and cell viability assay, and applied it to screen a library consisting 1528 FDA-approved drugs. Cetilistat (anti-pancreatic lipase), diiodohydroxyquinoline (anti-parasitic), abiraterone acetate (synthetic androstane steroid), and bexarotene (antineoplastic retinoid) exhibited potent in vitro anti-SARS-CoV-2 activity (EC50 1.13-2.01 µM). Bexarotene demonstrated the highest Cmax:EC50 ratio (1.69) which was higher than those of chloroquine, hydroxychloroquine, and ivermectin. These results demonstrated the efficacy of the two-tier screening system and identified potential COVID-19 treatments which can achieve effective levels if given by inhalation or systemically depending on their pharmacokinetics.

[Guideline for Long-Term Oxygen Therapy - S2k-Guideline Published by the German Respiratory Society]. / Leitlinie zur Langzeit-Sauerstofftherapie.

Long-term oxygen therapy is of great importance both for reducing mortality and for improving performance in patients with chronic lung diseases. The prerequisites for Long-term oxygen therapy are adequate diagnostics and clearly defined indication. A causal distinction into chronic hypoxaemic and hypercapnic respiratory failure is reasonable, from which the differential indication for non-invasive ventilation results.The revised guideline covers the diagnostics and indication of chronic lung and heart diseases, the role of oxygen in terminal illness and gives a detailed description of available oxygen devices. The guideline is intended to help avoid undersupply, oversupply and false prescriptions. Furthermore, the chapter "Postacute Oxygen Therapy" discusses the procedure, relevant in everyday life, but not yet clearly defined, for prescribing oxygen therapy for the home at the end of an inpatient stay. Another important point, the correct prescription of mobile oxygen systems, is also presented in the guideline. This document is a revised version of the guideline for longterm oxygen therapy and replaces the version of 2008.

[Exercise Training in Patients with Pulmonary Hypertension: A Systematic Review and Meta-analysis]. / Körperliches Training bei pulmonaler Hypertonie ­ ein systematisches Review mit Metaanalyse.

BACKGROUND: Pulmonary hypertension (PH) is defined as an elevation of mean pulmonary-arterial pressure by > 20 mmHg at rest, which may lead to right heart failure. Physical exercise has not been regularly recommended for PH patients for fear of symptom deterioration or occurrence of exercise-induced adverse events. METHODS: Three electronic databases were searched for randomized, controlled trials investigating exercise training in PH patients using the following keywords: "pulmonary hypertension" OR "pulmonary arterial hypertension" AND "exercise" OR "pulmonary rehabilitation" AND "randomized". RESULTS: Five studies involving 187 PH patients were included in this systematic review. Exercise programs lasted for 3 - 12 weeks (e. g. endurance training for 10 - 45 minutes; 60 - 80 % of the peak heart rate). PH patients significantly improved exercise capacity compared to controls in 6-minute walk distance (+ 45 m; 95 % CI: 26 m - 64 m) or peak oxygen consumption (+ 2.3 ml/kg/min; 95 % CI: 1.8 - 2.9 ml/kg/min), both p < 0.001. Also, physical and mental quality of life improved significantly by exercise training. No exercise-induced adverse events were observed. CONCLUSION: Supervised exercise training can safely and significantly improve physical performance and quality of life in clinically stable PH patients with optimal drug treatment. However, larger studies including a wider range of PH are mandatory.

[Guideline for the Diagnosis and Treatment of COPD Patients - Issued by the German Respiratory Society and the German Atemwegsliga in Cooperation with the Austrian Society of Pneumology]. / Leitlinie zur Diagnostik und Therapie von Patienten mit chronisch obstruktiver Bronchitis und Lungenemphysem (COPD).

This document is a revision of the guideline for diagnosis and treatment of COPD that replaces the version from 2007. A multitude of recent reports regarding risk factors, diagnosis, assessment, prevention and pharmacological as well as non-pharmacological treatment options made a major revision mandatory. The new guideline is based on the GOLD document taking into account specifics in Germany and Austria.

[In Exchange with COPD Patients: Towards a Patient-Oriented Communication]. / Im Gespräch mit COPD-Patienten: patientenzentriert kommunizieren.

The quality of life can be severely impaired in patients with COPD. In addition to physical restraints, they often suffer from psychological comorbidities (e. g. anxiety, depression). Psychological comorbidities are often associated with dysfunctional beliefs about the illness and its treatment. Such dysfunctional beliefs, in turn, are likely to negatively affect patients' quality of life as well as their communication with physicians and their illness behavior in general. It is therefore important for physicians to adapt their communication to account for patients' dysfunctional beliefs. This paper will review the role of dysfunctional beliefs and psychological comorbidities in COPD. It will also elaborate on potential ways to adjust communication between physicians and patients accordingly.

[Guideline for the Diagnosis and Treatment of Asthma - Guideline of the German Respiratory Society and the German Atemwegsliga in Cooperation with the Paediatric Respiratory Society and the Austrian Society of Pneumology]. / S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma.

The present guideline is a new version and an update of the guideline for the diagnosis and treatment of asthma, which replaces the previous version for german speaking countries from the year 2006. The wealth of new data on the pathophysiology and the phenotypes of asthma, and the expanded spectrum of diagnostic and therapeutic options necessitated a new version and an update. This guideline presents the current, evidence-based recommendations for the diagnosis and treatment of asthma, for children and adolescents as well as for adults with asthma.

[Long-term oxygen therapy (LTOT)--what should physicians, homecare-providers and health insurance companies know?]. / Die Langzeit-Sauerstoff-Therapie (LTOT) - Was sollten Arzt, Versorger und Krankenkasse wissen?

Long-term oxygen treatment (LTOT) has been demonstrated to improve prognosis in patients with chronic respiratory insufficiency. In terms of pathogenesis, improved oxygenation, reduction of pulmonary artery pressure as well as reduction of respiratory work are important. Since there are considerable differences between the LTOT systems, individually tailored therapy is needed. In particular, the mobility aspects of the patients must be taken into consideration. It is important to distinguish between stationary/mobile devices with a liquid oxygen system and stationary/mobile devices with oxygen concentrator. Oxygen titration should be performed in relation to rest and activity phases (e. g. 6 minute walk test) as well as in relation to the sleep phase. Employing devices with demand-controlled valves should be critically examined. This can be undertaken only under physician orders and requires continuous monitoring.

Pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis--a review.

Among the various types of interstitial lung diseases, idiopathic pulmonary fibrosis (IPF) is the most common disorder and has a poor prognosis and a limited response to pharmacological treatment. In patients with IPF, functional exercise tolerance and quality of life have been shown to be significantly decreased. Current IPF guidelines suggest only a weak recommendation for pulmonary rehabilitation (PR). However, PR is regarded as a reasonable choice for the majority of patients with IPF. This review will summarize all of the available studies that have investigated the effects of PR in patients with IPF so far. Although only a small number of studies have been published to date, most studies have found significant short-term improvements in functional exercise capacity, quality of life, and level of perceived dyspnea. Long-term improvements or maintenance strategies of PR in IPF patients have not been adequately investigated yet. Up to now there is still no sufficient evidence for the recommendation of PR in IPF. However, physical training seems to be the major component of all PR programs. The current review will discuss potential exercise training regimens for patients with IPF and suggest additional useful modalities of a specific multidisciplinary PR program for IPF patients. Based on the current literature and our own experience, this article will try to highlight the importance of PR as an additional, beneficial therapeutic option for patients with IPF.

[COPD-specific anxiety and depressive symptoms in COPD patients]. / Krankheitsbezogene Ängste und Depressivität bei COPD-Patienten.

The aim of the present study was to analyze the associations between COPD-specific anxiety and depressive symptoms in COPD patients. Anxiety, as well as depression, is a prevalent comorbid complication in COPD. Either can have a negative impact on patients' experience and the course of disease. So far, assessment in studies has exclusively focused on anxiety in general and not on disease-related fears. The present study comprised a sample of ninety-six patients suffering from COPD (GOLD III/IV). Results of the MANOVA showed higher COPD-specific anxiety in patients with depressive symptoms than in patients without depressive symptoms. Depressive patients showed a higher fear of social isolation, dyspnea related fear, fear of movement and fear of progression of disease. There were no differences between the two groups with regard to functional parameters (FEV 1 % pred.; 6-minute-walk-test). Overall, our study shows the necessity of the assessment of COPD-specific fears related to depression to guarantee an adequate treatment.

[Fear of progression and end-of-life fear in COPD patients]. / Progredienzangst und End-of-Life-Ängste bei COPD-Patienten.

Anxiety and depression are prevalent comorbid conditions in COPD. Furthermore, diseases related anxieties (fear of progression, end-of-life fear) occur very often. Anxiety can have a negative impact on patients' quality of life and is sometimes even considered as a risk factor for re-hospitalisation. There are only a few studies that focus on disease related anxieties in COPD. The aim of our study was to investigate the associations between disease related anxieties (fear of progression, end-of-life fear), psychological health status and quality of life in COPD patients. 132 patients with COPD (GOLD II-IV) participated in the study. Results of a MANOVA showed no differences between diseases related anxieties among patients with different disease severity (GOLD II-IV). Furthermore, the results showed significant associations between end-of-life fear, fear of progression, depression and quality of life. Further analyses showed that there is a need for managing end-of-life fears and improving end-of-life care. Overall, our study showed, that health disease related anxieties play an important role in COPD and still do not receive enough attention.

Detection and Establishment of Aedes notoscriptus (Diptera: Culicidae) Mosquitoes in Southern California, United States.

Aedes notoscriptus (Skuse), the Australian backyard mosquito, is a pestiferous daytime-biting species native to Australia and the surrounding southwestern Pacific region. It is suspected to play a role in the transmission of several arboviruses and is considered a competent vector of dog heartworm, Dirofilaria immitis (Leidy). This highly adaptable mosquito thrives in natural and artificial water-holding containers in both forested and urbanized areas, from tropical to temperate climates, and has benefitted from a close association with humans, increasing in abundance within its native range. It invaded and successfully established in New Zealand as well as in previously unoccupied temperate and arid regions of Australia. Ae. notoscriptus was discovered in Los Angeles County, CA, in 2014, marking the first time this species had been found outside the southwestern Pacific region. By the end of 2019, immature and adult mosquitoes had been collected from 364 unique locations within 44 cities spanning three southern California counties. The discovery, establishment, and rapid spread of this species in urban areas may signal the global movement and advent of a new invasive container-inhabiting species. The biting nuisance, public health, and veterinary health implications associated with the invasion of southern California by this mosquito are discussed.

Vocal cord dysfunction: what do we know?

Vocal cord dysfunction (VCD) is a disorder caused by episodic unintentional paradoxical adduction of the vocal cords, which may induce acute severe dyspnoea attacks not responsive to conventional asthma therapy. The aetiology of VCD is complex and often multifactorial. The essential pathophysiology is that of a hyperfunctional laryngeal reflex to protect the lower airway as a result of any combination of post-nasal drip, gastro-oesophageal reflux, laryngopharyngeal reflux and/or psychological conditions. Laryngoscopic demonstration of the paradoxical motion while wheezing or stridorous is considered the diagnostic gold standard. Speech therapy, including the use of special relaxed-throat breathing patterns is effective for VCD that is purely of the functional nature. Knowledge of the clinical features of VCD and identifying factors that may be contributing to the development of VCD can provide adequate clues to the correct diagnosis and management.

[Pulmonary rehabilitation before and after lung transplantation]. / Pneumologische Rehabilitation vor und nach Lungentransplantation.

Pulmonary rehabilitation of patients with advanced lung diseases especially with COPD patients has become more important over past years. For patients in which lung transplantation is indicated major studies concerning pre- and postoperative rehabilitation are still missing. Nevertheless, growing evidence suggests that training therapy and other components of comprehensive rehabilitation should be an essential part of the whole concept in order to augment the therapeutic success of LTx. The time prior to LTx may be used as "bridging to transplant" by improving strength, endurance and mobility. Intensive motivation and knowledge transfer can prepare patients as good candidates. The rehabilitation after LTx aims at regaining physical abilities and health related quality of life using the increased breathing capacities. The manuscript presents the importance, aims and specific features of rehabilitation prior to and following LTx. Finally the therapeutic concept will be discussed with regard to the economic burden and the limited resources in lung transplantation.

[Special training therapy to reduce inflammation in Anti-Jo-1 syndrome]. / Spezielle Trainingstherapie zur Reduktion der Inflammation bei Anti-Jo-1-Syndrom.

A 46-year-old patient was frequently seen with a medically treated Anti-Jo-1 syndrome. The patient had already been treated with azathioprine and oral corticosteroids on account of decreasing lung function, dyspnoea, fatigue, and beginning signs of myositis. Although high doses of steroids and azathioprine were administered, the muscleskeletal syndromes increased steadily. The patient used to be an active long-distance runner (20 km), but now was unable to perform that kind of physical exercise. It was decided to start a treatment with the GalileoTM training device for active muscle training of the lower extremities. Before and after three months of training the following assessment was performed: measurement of health-related quality of life (St. Georges respiratory questionnaire, SGRQ), ultrasound measurement of the cross-sectional area of the quadriceps muscle, 6 minute walk test (6 MWT), lung function testing, and assessment of serum markers of inflammation (TNF-alpha, interleukin-8, CRP, CK, myoglobin). After only two months, training with the GalileoTM five times a week has improved the patient's conditions dramatically. The training will be continued.