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1.
Nature ; 604(7906): 553-556, 2022 04.
Article in English | MEDLINE | ID: mdl-35240676

ABSTRACT

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).


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , Antibodies, Viral , Humans , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
2.
Nature ; 602(7898): 676-681, 2022 02.
Article in English | MEDLINE | ID: mdl-35016198

ABSTRACT

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.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , Immune Evasion/immunology , SARS-CoV-2/immunology , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/blood , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Cell Line , Convalescence , Evolution, Molecular , Humans , Immune Sera/immunology , Inhibitory Concentration 50 , Models, Molecular , Mutation , Neutralization Tests , SARS-CoV-2/chemistry , SARS-CoV-2/classification , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
3.
J Med Entomol ; 59(1): 67-77, 2022 01 12.
Article in English | MEDLINE | ID: mdl-34617571

ABSTRACT

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.


Subject(s)
Aedes , Animal Distribution , Introduced Species , Mosquito Vectors , Animals , California , Dirofilaria immitis/physiology , Dirofilariasis/transmission , Female , Male
4.
Preprint in English | bioRxiv | ID: ppbiorxiv-463665

ABSTRACT

Extrapulmonary complications of different organ systems have been increasingly recognized in patients with severe or chronic Coronavirus Disease 2019 (COVID-19). However, limited information on the skeletal complications of COVID-19 is known, even though inflammatory diseases of the respiratory tract have been known to perturb bone metabolism and cause pathological bone loss. In this study, we characterized the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on bone metabolism in an established golden Syrian hamster model for COVID-19. SARS-CoV-2 causes significant multifocal loss of bone trabeculae in the long bones and lumbar vertebrae of all infected hamsters. The bone loss progressively worsens from the acute phase to the post-recovery phase. Mechanistically, the bone loss was associated with SARS-CoV-2-induced cytokine dysregulation which upregulates osteoclastic differentiation of monocyte-macrophage lineage. The pro-inflammatory cytokines further trigger a second wave of cytokine storm in the skeletal tissues to augment their pro-osteoclastogenesis effect. Our findings in this established hamster model suggest that pathological bone loss may be a neglected complication which warrants more extensive investigations during the long-term follow-up of COVID-19 patients. The benefits of potential prophylactic and therapeutic interventions against pathological bone loss should be further evaluated. O_FIG O_LINKSMALLFIG WIDTH=188 HEIGHT=200 SRC="FIGDIR/small/463665v1_ufig1.gif" ALT="Figure 1"> View larger version (81K): org.highwire.dtl.DTLVardef@ada9b8org.highwire.dtl.DTLVardef@1617fcaorg.highwire.dtl.DTLVardef@cdcd3org.highwire.dtl.DTLVardef@75a0ab_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphical abstractSARS-CoV-2 infection causes pathological bone loss in golden Syrian hamsters through induction of cytokine storm and inflammation-induced osteoclastogenesis.

5.
Pneumologie ; 75(3): 191-200, 2021 Mar.
Article in German | MEDLINE | ID: mdl-33728628

ABSTRACT

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.


Subject(s)
Asthma , Pulmonary Medicine , Adolescent , Adult , Asthma/diagnosis , Asthma/drug therapy , Asthma/epidemiology , Austria , Child , Humans , Societies, Medical
7.
Pneumologie ; 74(12): 813-841, 2020 Dec.
Article in German | MEDLINE | ID: mdl-33291162

ABSTRACT

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.


Subject(s)
Lung Diseases , Noninvasive Ventilation , Oxygen Inhalation Therapy/standards , Practice Guidelines as Topic , Pulmonary Disease, Chronic Obstructive/therapy , Respiratory Insufficiency , Societies, Medical/standards , Germany , Humans , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/therapy , Time Factors
8.
Pharmacol Res ; 159: 104960, 2020 09.
Article in English | MEDLINE | ID: mdl-32473310

ABSTRACT

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.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus , Coronavirus Infections/drug therapy , Drug Evaluation, Preclinical/methods , Pneumonia, Viral/drug therapy , Androstenes/pharmacology , Animals , Benzoxazines/pharmacology , Betacoronavirus/drug effects , Betacoronavirus/physiology , Bexarotene/pharmacology , COVID-19 , Caco-2 Cells , Cell Survival/drug effects , Chlorocebus aethiops , Coronavirus Infections/virology , Cytopathogenic Effect, Viral/drug effects , Databases, Pharmaceutical , Drug Approval , Drug Repositioning , Enzyme-Linked Immunosorbent Assay , Humans , Iodoquinol/pharmacology , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , United States , United States Food and Drug Administration , Vero Cells , Viral Load/drug effects , Virus Replication/drug effects , COVID-19 Drug Treatment
9.
ACS Infect Dis ; 6(7): 1745-1758, 2020 07 10.
Article in English | MEDLINE | ID: mdl-32329611

ABSTRACT

Zika virus (ZIKV) is an emerging flavivirus that may be associated with congenital anomalies in infected fetuses and severe neurological and genital tract complications in infected adults. Currently, antiviral treatments to revert these ZIKV-induced complications are lacking. ZIKV infection has recently been suggested to upregulate the host unfolded protein response, which may contribute to the congenital neurological anomalies. As an extension from these findings, we thoroughly investigated the ZIKV-induced unfolded protein response using a combination of the neuronal cell line, induced pluripotent stem cell-derived human neuronal stem and progenitor cells, and an interferon receptor-deficient A129 mouse model. Our results revealed a critical contribution of the inositol-requiring enzyme-1 (IRE1) arm of the unfolded protein response to ZIKV-induced neurological and testicular complications. Importantly, the inhibition of the IRE1 signaling pathway activation with KIRA6 (kinase-inhibiting RNAse attenuator 6), a selective small molecule IRE1 inhibitor that promotes cell survival, potently reverted the ZIKV-induced perturbations of the key gene expressions associated with neurogenesis and spermatogenesis in vitro and in vivo, highlighting the potential of IRE1 inhibition as a novel host-targeting antiviral strategy in combating against ZIKV-induced neurological and testicular pathologies.


Subject(s)
Zika Virus Infection , Zika Virus , Humans , Imidazoles , Inositol , Naphthalenes , Neurogenesis , Protein Serine-Threonine Kinases , Pyrazines , Spermatogenesis , Zika Virus Infection/drug therapy
10.
Pneumologie ; 73(11): 677-685, 2019 Nov.
Article in German | MEDLINE | ID: mdl-31715636

ABSTRACT

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.


Subject(s)
Exercise Therapy/methods , Exercise Tolerance , Exercise , Hypertension, Pulmonary/therapy , Randomized Controlled Trials as Topic , Humans , Hypertension, Pulmonary/psychology , Physical Fitness , Quality of Life/psychology , Treatment Outcome
11.
MMW Fortschr Med ; 161(Suppl 1): 20, 2019 Mar.
Article in German | MEDLINE | ID: mdl-30912068
12.
Pneumologie ; 72(4): 253-308, 2018 Apr.
Article in German | MEDLINE | ID: mdl-29523017

ABSTRACT

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.


Subject(s)
Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Medicine/standards , Societies, Medical , Austria , Evidence-Based Medicine , Germany , Humans
13.
J Am Mosq Control Assoc ; 34(2): 93-98, 2018 06.
Article in English | MEDLINE | ID: mdl-31442161

ABSTRACT

Since Aedes albopictus was discovered in 2011 in the San Gabriel Valley it has become widespread despite the "harsh" environmental conditions and intense efforts to control or eliminate it. Species introduced into a new area may survive, thrive, or disappear depending on whether its new environment is suitable. The San Gabriel Valley Mosquito and Vector Control District expended considerable resources from 2011 to 2015 to eradicate this invasive species or, at a minimum, control and manage its spread. Despite the intense effort, the distribution of Ae. albopictus steadily expanded. Over those 5 years this increase shifted from a geometric to exponential pattern. What enabled Ae. albopictus to survive initially, become established, and then expand their distribution when ecological conditions in southern California were considered hostile for this invasive species? This study explores several biological characteristics including skip oviposition, installment egg hatching, and variable larval development that may have helped Ae. albopictus flourish in its new environment.


Subject(s)
Animal Distribution , Anopheles/physiology , Life History Traits , Mosquito Vectors/physiology , Animals , California , Introduced Species , Population Dynamics
14.
Pneumologie ; 71(12): 849-919, 2017 12.
Article in German | MEDLINE | ID: mdl-29216678

ABSTRACT

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.


Subject(s)
Asthma/diagnosis , Asthma/therapy , Asthma/classification , Asthma/etiology , Austria , Germany , Humans , Prognosis , Risk Factors , Societies, Medical
15.
Pneumologie ; 71(12): 837-842, 2017 Dec.
Article in German | MEDLINE | ID: mdl-28982206

ABSTRACT

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.


Subject(s)
Communication , Patient-Centered Care/methods , Physician-Patient Relations , Pulmonary Disease, Chronic Obstructive/psychology , Adaptation, Psychological , Anxiety/diagnosis , Anxiety/psychology , Anxiety/therapy , Communication Barriers , Comorbidity , Culture , Depression/diagnosis , Depression/psychology , Depression/therapy , Humans , Illness Behavior , Long-Term Care/psychology , Oxygen Inhalation Therapy/psychology , Patient Compliance/psychology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/therapy , Quality of Life/psychology , Terminal Care/psychology
18.
Respir Med ; 113: 8-14, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27021574

ABSTRACT

BACKGROUND: The response of patients in a pulmonary rehabilitation (PR) is essentially good. However, not all patients benefit from PR to the same extent. In this analysis we wanted to identify the impact of gender and other factors on PR outcomes in patients with chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD). METHODS: Patients suffering from COPD (n = 1492) or ILD (n = 599), treated during an inpatient PR between 1997 and 2015, were analysed according to the effects of PR on exercise capacity and quality of life with regard to the impact of gender or other predictors by univariate and multivariate analyzes. RESULTS: In the group of COPD patients, 30% did not achieve the expected physical performance during the 6-min walk test (28% of female and 32% of male patients). However, the non-responders initially have had a higher 6-min walking distance (6-MWD) (p < 0.001) and both male and female showed a significant lower BODE index (p = 0.025) in the multivariate analysis. In the ILD-group, 37% females and 43% males were classified as non-responders with regard to the 6-MWD. Also in this group, the non-responders initially have had a higher 6-MWD (p < 0.001). All other variables (age, BMI, lung function, blood gases, C-reactive Protein, Haemoglobin or rehabilitation duration) had no influence on the outcome. CONCLUSION: Our study supports the positive effects of PR in COPD and ILD patients. In both groups, patients with the biggest limitations benefit most from PR. However, relevant gender differences or other predictors could not be found.


Subject(s)
Exercise Tolerance , Lung Diseases, Interstitial/rehabilitation , Pulmonary Disease, Chronic Obstructive/rehabilitation , Aged , Female , Humans , Inpatients , Lung Diseases, Interstitial/physiopathology , Male , Middle Aged , Predictive Value of Tests , Pulmonary Disease, Chronic Obstructive/physiopathology , Quality of Life , Retrospective Studies , Risk Factors , Sex Factors , Treatment Outcome
19.
Pneumologie ; 68(3): 193-8, 2014 Mar.
Article in German | MEDLINE | ID: mdl-24595853

ABSTRACT

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.


Subject(s)
Oxygen Inhalation Therapy/instrumentation , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency/therapy , Equipment Design , Equipment Failure Analysis , Evidence-Based Medicine , Home Care Services , Humans
20.
Respiration ; 86(2): 89-99, 2013.
Article in English | MEDLINE | ID: mdl-23942353

ABSTRACT

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.


Subject(s)
Exercise Therapy/methods , Exercise Tolerance/physiology , Idiopathic Pulmonary Fibrosis/rehabilitation , Quality of Life , Humans , Idiopathic Pulmonary Fibrosis/physiopathology
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