Search

Bronchiolitis obliterans syndrome (BOS), the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group), and 26 samples at or after BOS diagnosis (diagnosis group). An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group). We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 (POU2AF1), T-cell leukemia/lymphoma protein 1A (TCL1A), and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p

Background Immersive virtual reality (iVR)-based digital therapeutics are gaining clinical attention in the field of pain management. Based on known analogies between pain and dyspnoea, we investigated the effects of visual respiratory feedback on persistent dyspnoea in patients recovering from coronavirus disease 2019 (COVID-19) pneumonia. Methods We performed a controlled, randomised, single-blind, crossover proof-of-concept study (feasibility and initial clinical efficacy) to evaluate an iVR-based intervention to alleviate dyspnoea in patients recovering from COVID-19 pneumonia. Included patients reported persistent dyspnoea (≥5 on a 10-point scale) and preserved cognitive function (Montreal Cognitive Assessment score >24). Assignment was random and concealed. Patients received synchronous (intervention) or asynchronous (control) feedback of their breathing, embodied via a gender-matched virtual body. The virtual body flashed in a waxing and waning visual effect that could be synchronous or asynchronous to the patient's respiratory movements. Outcomes were assessed using questionnaires and breathing recordings. Results Study enrolment was open between November 2020 and April 2021. 26 patients were enrolled (27% women; median age 55 years, interquartile range (IQR) 18 years). Data were available for 24 of 26 patients. The median rating on a 7-point Likert scale of breathing comfort improved from 1 (IQR 2) at baseline to 2 (IQR 1) for synchronous feedback, but remained unchanged at 1 (IQR 1.5) for asynchronous feedback (p

IntroductionThe type of donation may affect how susceptible a donor kidney is to injury from pre-existing alloimmunity. Many centers are, therefore, reluctant to perform donor specific antibody (DSA) positive transplantations in the setting of donation after circulatory death (DCD). There are, however, no large studies comparing the impact of pre-transplant DSA stratified on donation type in a cohort with a complete virtual cross-match and long-term follow-up of transplant outcome.MethodsWe investigated the effect of pre-transplant DSA on the risk of rejection, graft loss, and the rate of eGFR decline in 1282 donation after brain death (DBD) transplants and compared it to 130 (DCD) and 803 living donor (LD) transplants.ResultsThere was a significant worse outcome associated with pre-transplant DSA in all of the studied donation types. DSA directed against Class II HLA antigens as well as a high cumulative mean fluorescent intensity (MFI) of the detected DSA showed the strongest association with worse transplant outcome. We could not detect a significant additive negative effect of DSA in DCD transplantations in our cohort. Conversely, DSA positive DCD transplants appeared to have a slightly better outcome, possibly in part due to the lower mean fluorescent intensity (MFI) of the pre-transplant DSA. Indeed when DCD transplants were compared to DBD transplants with similar MFI (

Healthcare workers have potentially been among the most exposed to SARS-CoV-2 infection as well as the deleterious toll of the pandemic. This study has the objective to differentiate the pandemic toll from post-acute sequelae of SARS-CoV-2 infection in healthcare workers compared to the general population.The study was conducted between April and July 2021 at the Geneva University Hospitals, Switzerland. Eligible participants were all tested staff, and outpatient individuals tested for SARS-CoV-2 at the same hospital. The primary outcome was the prevalence of symptoms in healthcare workers compared to the general population, with measures of COVID-related symptoms and functional impairment, using prevalence estimates and multivariable logistic regression models.Healthcare workers (n = 3083) suffered mostly from fatigue (25.5 %), headache (10.0 %), difficulty concentrating (7.9 %), exhaustion/burnout (7.1 %), insomnia (6.2 %), myalgia (6.7 %) and arthralgia (6.3 %). Regardless of SARS-CoV-2 infection, all symptoms were significantly higher in healthcare workers than the general population (n = 3556). SARS-CoV-2 infection in healthcare workers was associated with loss or change in smell, loss or change in taste, palpitations, dyspnea, difficulty concentrating, fatigue, and headache. Functional impairment was more significant in healthcare workers compared to the general population (aOR 2.28; 1.76–2.96), with a positive association with SARS-CoV-2 infection (aOR 3.81; 2.59–5.60).Symptoms and functional impairment in healthcare workers were increased compared to the general population, and potentially related to the pandemic toll as well as post-acute sequelae of SARS-CoV-2 infection. These findings are of concern, considering the essential role of healthcare workers in caring for all patients including and beyond COVID-19.

BackgroundPre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM).MethodsWe investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls.ResultsPre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR.ConclusionOur results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA.

Background and Objectives: Community-acquired respiratory virus (CARV) infections pose a serious risk for lung transplant recipients (LTR) as they are prone to severe complications. When the COVID-19 pandemic hit Switzerland in 2020, the government implemented hygiene measures for the general population. We investigated the impact of these measures on the transmission of CARV in lung transplant recipients in Switzerland. Materials and Methods: In this multicenter, retrospective study of lung transplant recipients, we investigated two time periods: the year before the COVID-19 pandemic (1 March 2019–29 February 2020) and the first year of the pandemic (1 March 2020–28 February 2021). Data were mainly collected from the Swiss Transplant Cohort Study (STCS) database. Descriptive statistics were used to analyze the results. Results: Data from 221 Swiss lung transplant cohort patients were evaluated. In the year before the COVID-19 pandemic, 157 infections were diagnosed compared to 71 infections in the first year of the pandemic (decline of 54%, p < 0.001). Influenza virus infections alone showed a remarkable decrease from 17 infections before COVID-19 to 2 infections after the beginning of the pandemic. No significant difference was found in testing behavior; 803 vs. 925 tests were obtained by two of the three centers during the respective periods. Conclusions: We observed a significant decline in CARV infections in the Swiss lung transplant cohort during the first year of the COVID-19 pandemic. These results suggest a relevant impact of hygiene measures when implemented in the population due to the COVID-19 pandemic on the incidence of CARV infections.

Immunocompromised patients (ICPs) have a higher risk of developing severe forms of COVID-19 and experience a higher burden of complications and mortality than the general population. However, recent studies have suggested that the antibody response to SARS-CoV-2 mRNA vaccines could be highly variable among different ICPs. Using a collaborative, monocentric, prospective cohort study, we assessed anti-SARS-CoV-2 spike protein antibody titers following two and three doses of mRNA vaccines in four groups of ICPs (cancer [n = 232]: hematopoietic stem cell transplant [HSCT; n = 126] patients; people living with HIV [PLWH; n = 131]; and lung transplant [LT; n = 39] recipients) treated at Geneva University Hospitals; and healthy individuals (n = 49). After primo-vaccination, the highest anti-S antibody geometric mean titer (IU/mL) was observed in healthy individuals (2417 IU/mL [95% CI: 2327–2500]), the PLWH group (2024 IU/mL [95% CI:1854–2209]) and patients with cancer (840 IU/mL [95% CI: 625–1129]), whereas patients in the HSCT and LT groups had weaker antibody responses (198 IU/mL [95% CI: 108–361] and 7.3 IU/mL [95% CI: 2.5–22]). The booster dose conferred a high antibody response after 1 month in both PLWH (2500 IU/mL) and cancer patients (2386 IU/mL [95% CI: 2182–2500]), a moderate response in HSCT patients (521 IU/mL [95% CI: 306–885]) and a poor response in LT recipients (84 IU/mL [95% CI: 18–389]). Contemporary treatment with immunosuppressive drugs used in transplantation or chemotherapy was associated with a poor response to vaccination. Our findings confirmed the heterogeneity of the humoral response after mRNA vaccines among different ICPs and the need for personalized recommendations for each of these different groups.

A Hemiplegia Alternante da Infância é um distúrbio neurológico grave e uma doença rara (1 em cada 100.000 recém-nascidos), caracterizado por ataques repetidos transitórios de hemiplegia episódica ou tetraplegia que podem durar minutos a horas, acompanhados por outros sintomas paroxísticos como anormalidades oculomotoras e autonômicas, distúrbios do movimento como ataxia, comprometimento cognitivo progressivo, convulsões, distonia e coreia. Os tratamentos atuais são amplamente sintomáticos. Neste relato de caso, apresentamos paciente do sexo feminino, 18 anos, na qual aos 10 meses apresentou o primeiro episódio aparente de crise convulsiva com versão ocular. O eletroencefalograma e tomografia computadorizada não revelaram anormalidades e foram administradas diversas medicações como fenobarbital, carbamazepina, valproato de sódio, topiramato, dicloridrato de flunarizina, clonazepam, cipro-heptadina e pizotifeno, todos sem resultado. Devidos aos sintomas extrapiramidais, paciente passou a utilizar biperideno, apresentando não só melhora da distonia, mas também no número de crises hemiplégicas. Aos 13 anos, ela foi diagnosticada com Hemiplegia Alternante da Infância na mutação patogênica missense de novo c.2415CG (p.Asp805Glu) no gene ATP1A3 apresentando boa resposta ao tratamento com cloridrato de biperideno.

Background: Lung ultrasound (LUS) has a good performance with a high sensitivity and specificity for the diagnosis of pneumonia compared with chest X-ray, and it has been extensively used to assess patients during the COVID-19 pandemic. This study aims to evaluate the potential advantages of the regular use of LUS for the assessment of the severity and prognosis of COVID-19 pneumonia and to propose an adapted protocol with its inclusion in current local validated and published guidelines.Methods: This is a single-center prospective study conducted during the first (April–May 2020) and second (October 2020–January 2021) waves of the SARS-CoV2 pandemic in Switzerland. All adult patients presenting to dedicated test centers with a suspicion of mild-to-moderate COVID-19 pneumonia and not requiring hospitalization at the time of diagnosis were included. Patients with confirmed COVID-19 pneumonia were referred to an ambulatory follow-up unit at our institution for reassessment, with the inclusion of the use of LUS in a random selection. Descriptive statistics were calculated for demographics using percentages, means, and standard deviations according to the distribution of variables.Results: Eighty-eight ambulatory patients with a confirmed COVID-19 pneumonia were included (men = 57 [59%]; mean age, 52.1 ± 13.5 years). Among these, 19 (21%) were hospitalized and none died. Twenty-five lung assessments by ultrasound were performed during the follow-up consultation. All were consistent with the clinical examination and confirmed the clinician's opinion.Conclusion: The use of a standardized pleuro-pulmonary ultrasound protocol for ambulatory patients with COVID-19 could help to reduce the use of chest X-rays and improve overall management at the time of referral and eventual follow-up. However, a specific study including LUS in a systematic approach should be performed to evaluate the outcome of patients according to findings.

Obesity has complex links to respiratory health. Mendelian randomization (MR) enables assessment of causality of body mass index (BMI) effects on airflow obstruction and mid-expiratory flow. In the adult SAPALDIA cohort, recruiting 9,651 population-representative samples aged 18–60 years at baseline (female 51%), BMI and the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) as well as forced mid-expiratory flow (FEF25–75%) were measured three times over 20 follow-up years. The causal effects of BMI in childhood and adulthood on FEV1/FVC and FEF25–75% were assessed in predictive (BMI averaged over 1st and 2nd, lung function (LF) averaged over 2nd and 3rd follow-up; N = 2,850) and long-term cross-sectional models (BMI and LF averaged over all follow-ups; N = 2,728) by Mendelian Randomization analyses with the use of weighted BMI allele score as an instrument variable and two-stage least squares (2SLS) method. Three different BMI allele scores were applied to specifically capture the part of BMI in adulthood that likely reflects tracking of genetically determined BMI in childhood. The main causal effects were derived from models containing BMI (instrumented by BMI genetic score), age, sex, height, and packyears smoked as covariates. BMI interactions were instrumented by the product of the instrument (BMI genetic score) and the relevant concomitant variable. Causal effects of BMI on FEV1/FVC and FEF25–75% were observed in both the predictive and long-term cross-sectional models. The causal BMI- LF effects were negative and attenuated with increasing age, and stronger if instrumented by gene scores associated with childhood BMI. This non-standard MR approach interrogating causal effects of multiplicative interaction suggests that the genetically rooted part of BMI patterns in childhood may be of particular relevance for the level of small airway function and airflow obstruction later in life. The methodological relevance of the results is first to point to the importance of a life course perspective in studies on the etiological role of BMI in respiratory health, and second to point out novel methodological aspects to be considered in future MR studies on the causal effects of obesity related phenotypes.

Rationale and objectives Prone positioning as a complement to oxygen therapy to treat hypoxaemia in coronavirus disease 2019 (COVID-19) pneumonia in spontaneously breathing patients has been widely adopted, despite a lack of evidence for its benefit. We tested the hypothesis that a simple incentive to self-prone for a maximum of 12 h per day would decrease oxygen needs in patients admitted to the ward for COVID-19 pneumonia on low-flow oxygen therapy. Methods 27 patients with confirmed COVID-19 pneumonia admitted to Geneva University Hospitals were included in the study. 10 patients were randomised to self-prone positioning and 17 to usual care. Measurements and main results Oxygen needs assessed by oxygen flow on nasal cannula at inclusion were similar between groups. 24 h after starting the intervention, the median (interquartile range (IQR)) oxygen flow was 1.0 (0.1–2.9) L·min−1 in the prone position group and 2.0 (0.5–3.0) L·min−1 in the control group (p=0.507). Median (IQR) oxygen saturation/fraction of inspired oxygen ratio was 390 (300–432) in the prone position group and 336 (294–422) in the control group (p=0.633). One patient from the intervention group who did not self-prone was transferred to the high-dependency unit. Self-prone positioning was easy to implement. The intervention was well tolerated and only mild side-effects were reported. Conclusions Self-prone positioning in patients with COVID-19 pneumonia requiring low-flow oxygen therapy resulted in a clinically meaningful reduction of oxygen flow, but without reaching statistical significance.

Previous research has shown that the built environment plays a crucial role for health-related quality of life (HRQoL) and health care utilization. But, there is limited evidence on the independence of this association from lifestyle and social environment. The objective of this cross-sectional study was to investigate these associations, independent of the social environment, physical activity and body mass index (BMI). We used data from the third follow-up of the Swiss study on Air Pollution and Lung and Heart diseases In Adults (SAPALDIA), a population based cohort with associated biobank. Covariate adjusted multiple quantile and polytomous logistic regressions were performed to test associations of variables describing the perceived built environment with HRQoL and health care utilization. Higher HRQoL and less health care utilization were associated with less reported transportation noise annoyance. Higher HRQoL was also associated with greater satisfaction with the living environment and more perceived access to greenspaces. These results were independent of the social environment (living alone and social engagement) and lifestyle (physical activity level and BMI). This study provides further evidence that the built environment should be designed to integrate living and green spaces but separate living and traffic spaces in order to improve health and wellbeing and potentially save health care costs.

BackgroundThe symptomatic response to continuous positive airway pressure (CPAP) therapy in COPD-obstructive sleep apnea overlap syndrome (OVS) compared to OSA syndrome (OSA) alone has not been well studied so far. The aim of this study is to explore main differences in the clinical response to CPAP treatment in OVS compared to OSA alone.Study design and methodsUsing prospective data from the French National Sleep Apnea Registry, we conducted an observational study among 6320 patients with moderate-to-severe OSA, available spirometry, and at least one follow-up visit under CPAP therapy.ResultsCPAP efficacy measured on the residual apnea-hypopnea index and median adherence were similar between OVS and OSA patients. In both groups, the overall burden of symptoms related to sleep apnea improved with CPAP treatment. In a multivariable model adjusted for age, gender, body mass index, adherence to treatment and residual apnea-hypopnea index, OVS was associated with higher odds for persistent morning headaches (OR: 1.37 [95% CI; 1.04; 1.79]; P = 0.02), morning tiredness (OR: 1.33 [95% CI: 1.12; 1.59]; PInterpretationCPAP therapy was effective in normalizing the apnea-hypopnea index and significantly improved OSA-related symptoms, regardless of COPD status. CPAP should be offered to patients with OVS on a trial basis as a significant improvement in OSA-related symptoms can be expected, although the range of response may be less dramatic than in OSA alone.

BACKGROUND:Barriers and motives towards physical activity (PA) in lung transplant (LTx) recipients with cystic fibrosis (CF) are largely unknown. We aimed to explore perceptions towards PA in LTx recipients with CF to better understand individuals' needs and preferences. METHODS:Participants completed an online survey at two Swiss LTx and one follow-up shared care centre between June and December 2018. RESULTS:One hundred and eleven individuals completed the survey (87.4% response rate). Overall, survey participants perceive PA as important for their daily life and health. Perceived motives of PA were improving muscle strength, endurance and quality of life (QoL), to feel better, fun, to achieve personal goals and having more energy for everyday life. Fatigue was the most common perceived barrier to PA and associated with poorer QoL (r = -0.43, p

BackgroundMore advanced knowledge is needed on how COPD alters the clinical presentation of obstructive sleep apnea (OSA) and how the association of both diseases, known as 'overlap syndrome' (OVS), impacts on cardiovascular health.ObjectiveTo investigate differences between patients with OVS and those with moderate-to-severe OSA alone.MethodsA cross-sectional study conducted in the French National Sleep Apnea Registry between January 1997 and January 2017. Univariable and multivariable logistic regression models were used to compare OVS versus OSA alone on symptoms and cardiovascular health.Results46,786 patients had moderate-to-severe OSA. Valid spirometry was available for 16,466 patients: 14,368 (87%) had moderate-to-severe OSA alone and 2098 (13%) had OVS. A lower proportion of OVS patients complained of snoring, morning headaches and excessive daytime sleepiness compared to OSA alone (median Epworth Sleepiness Scale score: 9 [interquartile range (IQR) 6-13] versus 10 (IQR 6-13), respectively; P ConclusionsIn adults with moderate-to-severe OSA, OVS was minimally symptomatic, but exhibited higher odds for prevalent coronary heart disease, heart failure and peripheral arteriopathy.

AIM Various scoring systems aim to assess the quality of organs donated for transplantation on the basis of patient characteristics, clinical examination and laboratory results. How well such scoring systems reflect the practice in lung transplantation in Switzerland has never been studied. Therefore, we evaluated two scoring systems for their ability to predict whether or not donor lungs are accepted by the two Swiss lung transplant centres. METHODS We retrospectively analysed patient data of adult deceased organ donors in Switzerland between 1 July 2007 and 30 June 2014. Included were all donors from whom at least one organ was transplanted. We evaluated two lung donor quality scores, the multicentre-developed Eurotransplant donor score (EDS), and the single-centre-developed Zurich donor score (ZDS). Both scores were slightly adapted to be applicable to Swiss deceased organ donor data. We evaluated whether these scores can predict whether lungs were transplanted or refused by Swiss transplant centres, using univariate logistic regression. We further assessed their discriminative power by calculating the area under the receiver operating characteristic curve (AUC). RESULTS Of the 635 donors included in our analysis, 295 (46%) were accepted as lung donors by one of the two lung transplant centres in Switzerland. Our analysis showed that both scores can predict whether or not a donor lung is likely to be accepted for transplantation in Switzerland. As the score value of a donor increases, the odds of the lung being transplanted significantly decreases (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.51–0.65 for the adapted EDS; OR 0.35, 95% CI 0.28–0.43 for the adapted ZDS). This effect is slightly more pronounced in the adapted ZDS than in the adapted EDS. The discriminatory power of the scores from the AUC was 0.719 (95% CI 0.680–0.758) for the adapted EDS, and 0.723 (95% CI 0.681–0.760) for the adapted ZDS, which for both was deemed fair discrimination. CONCLUSIONS Both scoring systems are able to predict whether or not donor lungs are accepted by the two Swiss lung transplant centres. As an alternative to adapting an established scoring system, a national lung quality score could be derived de novo. This could be based on a logistic regression analysis including the most relevant donor characteristics. However, such a new score would need to be validated on an independent sample and ideally tested for its predictive value in terms of post-transplantation outcome.

Foram avaliados os efeitos de um programa de intervenção com reeducação postural global (RPG) e um período sem tratamento (8 semanas) pela análise cinemática e avaliação do equilíbrio estático e dinâmico de um adulto com Paralisia Cerebral (PC). Foram realizadas avaliações do equilíbrio por meio da Escala de Equilíbrio de Berg e avaliações cinemáticas da marcha, nas quais foram analisadas variáveis espaçotemporais e angulares. Essas avaliações foram feitas no início e no final de cada período de intervenção. Para a caracterização dos parâmetros analisados foi utilizada a estatística descritiva (média e desvio padrão). O sujeito estudado apresentou melhora do equilíbrio após o período de intervenção e, em relação às variáveis angulares, foi verificada diminuição da extensão de quadril e menor inclinação de tronco. Com a melhora do equilíbrio, da extensão do quadril e do alinhamento do tronco do paciente tratado, sugere-se que a intervenção com o método RPG pode ser eficaz como conduta fisioterapêutica para a PC, porém resultados mais eficazes podem estar associados com o tratamento contínuo por esse método, uma vez que durante os intervalos da intervenção, observou-se diminuição do equilíbrio.

Dual-energy computed tomography (DECT) angiography of the chest provides a combined morphological and functional analysis of the lung, usually obtained in a single acquisition without extra radiation or injection of extra intravenous iodine contrast. The parenchymal iodine maps generated by DECT are well correlated with scintigraphy, and are becoming an essential tool for evaluating patients with pulmonary vascular diseases. With a single DECT acquisition, complete imaging of pulmonary hypertension is now available, displaying vascular anatomy, parenchymal morphology and functional assessment. Triangular pulmonary perfusion defects in chronic thromboembolic pulmonary hypertension may be clearly analysed even in the presence of distal arterial occlusion. Perfusion heterogeneities seen in patients with pulmonary arterial hypertension reflect mosaic perfusion and may be helpful for the diagnosis, severity assessment and prognosis of the disease. Vascular or parenchymal abnormalities can also be analysed with perfusion defects to determine their aetiology. Pulmonary arterial hypertension due to congenital heart disease can be assessed with a single DECT, even in the neonatal population. Furthermore, new applications are emerging with ventilation imaging or myocardial perfusion imaging obtained by DECT and should be considered. In conclusion, DECT of the thorax enables the simultaneous and noninvasive assessment of vascular anatomy, parenchymal morphology and functional pulmonary imaging in various groups of PH.

Polygenic obesity in Solid Organ Transplant (SOT) populations is considered a risk factor for the development of metabolic abnormalities and graft survival. Few studies to date have studied the genetics of weight gain in SOT recipients. We aimed to determine whether weighted genetic risk scores (w-GRS) integrating genetic polymorphisms from GWAS studies (SNP group#1 and SNP group#2) and from Candidate Gene studies (SNP group#3) influence BMI in SOT populations and if they predict ≥10% weight gain (WG) one year after transplantation. To do so, two samples (nA = 995, nB = 156) were obtained from naturalistic studies and three w-GRS were constructed and tested for association with BMI over time. Prediction of 10% WG at one year after transplantation was assessed with models containing genetic and clinical factors.w-GRS were associated with BMI in sample A and B combined (BMI increased by 0.14 and 0.11 units per additional risk allele in SNP group#1 and #2, respectively, p-values

Rhinoviruses and enteroviruses are leading causes of respiratory infections. To evaluate genotypic diversity and identify forces shaping picornavirus evolution, we screened persons with respiratory illnesses by using rhinovirus-specific or generic real-time PCR assays. We then sequenced the 5′ untranslated region, capsid protein VP1, and protease precursor 3CD regions of virus-positive samples. Subsequent phylogenetic analysis identified the large genotypic diversity of rhinoviruses circulating in humans. We identified and completed the genome sequence of a new enterovirus genotype associated with respiratory symptoms and acute otitis media, confirming the close relationship between rhinoviruses and enteroviruses and the need to detect both viruses in respiratory specimens. Finally, we identified recombinants among circulating rhinoviruses and mapped their recombination sites, thereby demonstrating that rhinoviruses can recombine in their natural host. This study clarifies the diversity and explains the reasons for evolution of these viruses.

Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response. Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections. Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type. In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month. Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5'UTR polypyrimidine tract and the VP2 immunogenic site 2. These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers.