Publications of Julien GUIOT
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See detailAge-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality.
Nakanishi, Tomoko; Pigazzini, Sara; Degenhardt, Frauke et al

in Journal of Clinical Investigation (2021), Online ahead of print.

BACKGROUND: There is considerable variability in COVID-19 outcomes amongst younger adults-and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the ... [more ▼]

BACKGROUND: There is considerable variability in COVID-19 outcomes amongst younger adults-and some of this variation may be due to genetic predisposition. We characterized the clinical implications of the major genetic risk factor for COVID-19 severity, and its age-dependent effect, using individual-level data in a large international multi-centre consortium. METHOD: The major common COVID-19 genetic risk factor is a chromosome 3 locus, tagged by the marker rs10490770. We combined individual level data for 13,424 COVID-19 positive patients (N=6,689 hospitalized) from 17 cohorts in nine countries to assess the association of this genetic marker with mortality, COVID-19-related complications and laboratory values. We next examined if the magnitude of these associations varied by age and were independent from known clinical COVID-19 risk factors. FINDINGS: We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (hazard ratio [HR] 1·4, 95% confidence interval [CI] 1·2-1·6) and COVID-19 related mortality (HR 1·5, 95%CI 1·3-1·8). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (odds ratio [OR] 2·0, 95%CI 1·6-2·6), venous thromboembolism (OR 1·7, 95%CI 1·2-2·4), and hepatic injury (OR 1·6, 95%CI 1·2-2·0). Risk allele carriers ≤ 60 years had higher odds of death or severe respiratory failure (OR 2·6, 95%CI 1·8-3·9) compared to those > 60 years OR 1·5 (95%CI 1·3-1·9, interaction p-value=0·04). Amongst individuals ≤ 60 years who died or experienced severe respiratory COVID-19 outcome, we found that 31·8% (95%CI 27·6-36·2) were risk variant carriers, compared to 13·9% (95%CI 12·6-15·2%) of those not experiencing these outcomes. Prediction of death or severe respiratory failure among those ≤ 60 years improved when including the risk allele (AUC 0·82 vs 0·84, p=0·016) and the prediction ability of rs10490770 risk allele was similar to, or better than, most established clinical risk factors. INTERPRETATION: The major common COVID-19 risk locus on chromosome 3 is associated with increased risks of morbidity and mortality-and these are more pronounced amongst individuals ≤ 60 years. The effect on COVID-19 severity was similar to, or larger than most established risk factors, suggesting potential implications for clinical risk management. FUNDING: Funding was obtained by each of the participating cohorts individually. [less ▲]

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See detailClinical experience in anti-synthetase syndrome: a monocentric retrospective analytical study.
Maloir, Quentin ULiege; SEIDEL, Laurence ULiege; VON FRENCKELL, Christian ULiege et al

in Acta Clinica Belgica (2021)

OBJECTIVES: Anti-synthetase syndrome (ASS) is a rare autoimmune disorder combining autoantibodies and specific clinical manifestations. One of the particularities of ASS is the pleiomorphic radiological ... [more ▼]

OBJECTIVES: Anti-synthetase syndrome (ASS) is a rare autoimmune disorder combining autoantibodies and specific clinical manifestations. One of the particularities of ASS is the pleiomorphic radiological presentation seen at the initial work-up. Evaluating treatment response can also be challenging and requires specific clinical, functional, biological and radiological monitoring. For these reasons, it is fundamental to identify specific radiological and clinical features of ASS for improved diagnosis and therapeutic approaches.METHODS: We retrospectively studied all patients suffering from ASS in the CHU of Liège from 2008 to 2019. We analysed the clinical features, pulmonary function tests (PFTs), computed tomography (CT), and longitudinal evolution with regard to patient treatment.RESULTS: In the whole cohort of 30 patients, we identified 19 with anti-JO1 antibodies, 5 with anti-PL12 antibodies and 6 with anti-PL7 antibodies. The sex ratio was slightly in favour of males. Interestingly, PL-12 syndrome was more likely to be present in younger patients than those associated with other antibodies. Overall, 77% of the overall cohort exhibited specific pulmonary involvement without any significant difference with regard to the severity assessed by PFT at diagnosis. In contrast, the radiological presentation was pleomorphic for anti-JO1 syndrome, and anti-PL12 syndrome exhibited mainly ground-glass opacities (GGOs) and reticular abnormalities, while those with anti-PL7 antibodies showed reticulations and bronchiectasis. Longitudinal CT analysis mainly showed a reduction in consolidations and GGOs with specific therapies.CONCLUSION: In our single-centre retrospective study, we found different profiles for different autoantibodies according to age and radiological appearance. [less ▲]

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See detailSputum IL-25, IL-33 and TSLP, IL-23 and IL-36 in airway obstructive diseases. Reduced levels of IL-36 in eosinophilic phenotype.
Moermans, Catherine ULiege; Damas, K.; Guiot, Julien ULiege et al

in Cytokine (2021), 140

INTRODUCTION: Alarmins ((IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)) are known to promote Th2 inflammation and could be associated with eosinophilic airway infiltration. They may also play a ... [more ▼]

INTRODUCTION: Alarmins ((IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)) are known to promote Th2 inflammation and could be associated with eosinophilic airway infiltration. They may also play a role in airway remodeling in chronic airway obstructive diseases such as asthma and chronic obstructive pulmonary disease (COPD). IL-23 and IL-36 were shown to mediate the neutrophilic airway inflammation as seen in chronic airway obstructive diseases. OBJECTIVES: The purpose of this project was to determine the expression and the production of these cytokines from induced sputum (IS) in patients with chronic airway obstructive diseases including asthmatics and COPD. The relationship of the mediators with sputum inflammatory cellular profile and the severity of airway obstruction was assessed. METHODS: The alarmins (IL-25, IL-33 and TSLP) as well as IL-23 and IL-36 concentrations were measured in IS from 24 asthmatics and 20 COPD patients compared to 25 healthy volunteers. The cytokines were assessed by ELISA in the IS supernatant and by RT-qPCR in the IS cells. RESULTS: At protein level, no difference was observed between controls and patients suffering from airway obstructive diseases regarding the different mediators. IL-36 protein level was negatively correlated with sputum eosinophil and appeared significantly decreased in patients with an eosinophilic airway inflammation compared to those with a neutrophilic profile and controls. At gene level, only IL-36, IL-23 and TSLP were measurable but none differed between controls and patients with airway obstructive diseases. IL-36 and IL-23 were significantly increased in patients with an neutrophilic inflammatory profile compared to those with an eosinophilic inflammation and were correlated with sputum neutrophil proportions. None of the mediators were linked to airway obstruction. CONCLUSIONS: The main finding of our study is that patients with eosinophilic airway inflammation exhibited a reduced IL-36 level which could make them more susceptible to airway infections as IL-36 is implicated in antimicrobial defense. This study showed also an implication of IL-36 and IL-23 in airway neutrophilic inflammation in chronic airway obstructive diseases. [less ▲]

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See detailBreathomics to diagnose systemic sclerosis using thermal desorption and comprehensive two-dimensional gas chromatography high-resolution time-of-flight mass spectrometry
Zanella, Delphine ULiege; GUIOT, Julien ULiege; Stefanuto, Pierre-Hugues ULiege et al

in Analytical and Bioanalytical Chemistry (2021)

Systemic sclerosis is a rare autoimmune disease associated with rapidly evolving interstitial lung disease, responsible for the disease severity and mortality. Specific biomarkers enabling the early ... [more ▼]

Systemic sclerosis is a rare autoimmune disease associated with rapidly evolving interstitial lung disease, responsible for the disease severity and mortality. Specific biomarkers enabling the early diagnosis and prognosis associated with the disease progression are highly needed. Volatile organic compounds in exhaled breath are widely available and non-invasive and have the potential to reflect metabolic processes occurring within the body. Comprehensive two-dimensional gas chromatography coupled to high-resolution mass spectrometry was used to investigate the potential of exhaled breath to diagnose systemic sclerosis. The exhaled breath of 32 patients and 30 healthy subjects was analyzed. The high resolving power of this approach enabled the detection of 356 compounds in the breath of systemic sclerosis patients, which was characterized by an increase of mainly terpenoids and hydrocarbons. In addition, the use of 4 complementary statistical approaches (two-tailed equal variance ttest, fold change, partial least squares discriminant analysis, and random forest) resulted in the identification of 16 compounds that can be used to discriminate systemic sclerosis patients from healthy subjects. Receiver operating curves were generated that provided an accuracy of 90%, a sensitivity of 92%, and a specificity of 89%. The chemical identification of eight compounds predictive of systemic sclerosis was validated using commercially available standards. The analytical variations together with the volatile composition of room air were carefully monitored during the timeframe of the study to ensure the robustness of the technique. This study represents the first reported evaluation of exhaled breath analysis for systemic sclerosis diagnosis and provides surrogate markers for such disease. [less ▲]

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See detailCirculating Nucleosomes as Potential Markers to Monitor COVID-19 Disease Progression.
Cavalier, Etienne ULiege; Guiot, Julien ULiege; Lechner, Katharina et al

in Frontiers in molecular biosciences (2021), 8

The severity of coronavirus disease 2019 (COVID-19) varies significantly with cases spanning from asymptomatic to lethal with a subset of individuals developing Severe Acute Respiratory Syndrome (SARS ... [more ▼]

The severity of coronavirus disease 2019 (COVID-19) varies significantly with cases spanning from asymptomatic to lethal with a subset of individuals developing Severe Acute Respiratory Syndrome (SARS) and death from respiratory failure. To determine whether global nucleosome and citrullinated nucleosome levels were elevated in COVID-19 patients, we tested two independent cohorts of COVID-19 positive patients with quantitative nucleosome immunoassays and found that nucleosomes were highly elevated in plasma of COVID-19 patients with a severe course of the disease relative to healthy controls and that both histone 3.1 variant and citrullinated nucleosomes increase with disease severity. Elevated citrullination of circulating nucleosomes is indicative of neutrophil extracellular trap formation, neutrophil activation and NETosis in severely affected individuals. Importantly, using hospital setting (outpatient, inpatient or ICU) as a proxy for disease severity, nucleosome levels increased with disease severity and may serve as a guiding biomarker for treatment. Owing to the limited availability of mechanical ventilators and extracorporal membrane oxygenation (ECMO) equipment, there is an urgent need for effective tools to rapidly assess disease severity and guide treatment selection. Based on our studies of two independent cohorts of COVID-19 patients from Belgium and Germany, we suggest further investigation of circulating nucleosomes and citrullination as biomarkers for clinical triage, treatment allocation and clinical drug discovery. [less ▲]

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See detailYKL-40 as a new promising prognostic marker of severity in COVID infection.
Schoneveld, Lauranne ULiege; LADANG, Aurélie ULiege; HENKET, Monique ULiege et al

in Critical care (London, England) (2021), 25(1), 66

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See detailLa fibrose pulmonaire : des biomarqueurs à de nouveaux horizons thérapeutiques.
Guiot, Julien ULiege; HENKET, Monique ULiege; NJOCK, Makon-Sébastien ULiege et al

in Revue medicale de Liege (2021), 76(3), 166-172

Pulmonary fibrosis is a pathological entity still too little understood today, burdened with significant morbidity and mortality. Idiopathic pulmonary fibrosis is a complex diagnostic disease requiring a ... [more ▼]

Pulmonary fibrosis is a pathological entity still too little understood today, burdened with significant morbidity and mortality. Idiopathic pulmonary fibrosis is a complex diagnostic disease requiring a multidisciplinary approach and in some cases the performance of a lung biopsy. In addition, the early identification of the pathology remains the key in order to preserve lung function as much as possible. In this context and in view of the diagnostic difficulty, it seems essential to identify new biomarkers to help with the differential diagnosis, the evaluation of the prognosis and the response to treatment. In addition, the evolution of the pathology remaining inexorable despite anti-fibrotic treatments, it appears critical to be able to identify new potential therapeutic routes. [less ▲]

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See detailDoes Facemask Impact Diagnostic During Pulmonary Auscultation?
Uyttendaele, Vincent ULiege; GUIOT, Julien ULiege; Chase, J. Geoffrey et al

in IFAC-PapersOnLine (2021), 54(15), 1-580

Facemasks have been widely used in hospitals, especially since the emergence of the coronavirus 2019 (COVID-19) pandemic, often severely affecting respiratory functions. Masks protect patients from ... [more ▼]

Facemasks have been widely used in hospitals, especially since the emergence of the coronavirus 2019 (COVID-19) pandemic, often severely affecting respiratory functions. Masks protect patients from contagious airborne transmission, and are thus more specifically important for chronic respiratory disease (CRD) patients. However, masks also increase air resistance and thus work of breathing, which may impact pulmonary auscultation and diagnostic acuity, the primary respiratory examination. This study is the first to assess the impact of facemasks on clinical auscultation diagnostic. Lung sounds from 29 patients were digitally recorded using an electronic stethoscope. For each patient, one recording was taken wearing a surgical mask and one without. Recorded signals were segmented in breath cycles using an autocorrelation algorithm. In total, 87 breath cycles were identified from sounds with mask, and 82 without mask. Time-frequency analysis of the signals was used to extract comparison features such as peak frequency, median frequency, band power, or spectral integration. All the features extracted in frequency content, its evolution, or power did not significantly differ between respiratory cycles with or without mask. This early stage study thus suggests minor impact on clinical diagnostic outcomes in pulmonary auscultation. However, further analysis is necessary such as on adventitious sounds characteristics differences with or without mask, to determine if facemask could lead to no discernible diagnostic outcome in clinical practice. [less ▲]

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See detailA Blood Exosomal miRNA Signature in Acute Respiratory Distress Syndrome.
Parzibut, Gilles ULiege; Henket, Monique ULiege; Moermans, Catherine ULiege et al

in Frontiers in Molecular Biosciences (2021), 8

Acute respiratory distress syndrome (ARDS) is a diffuse, acute, inflammatory lung disease characterized by a severe respiratory failure. Recognizing and promptly treating ARDS is critical to combat the ... [more ▼]

Acute respiratory distress syndrome (ARDS) is a diffuse, acute, inflammatory lung disease characterized by a severe respiratory failure. Recognizing and promptly treating ARDS is critical to combat the high mortality associated with the disease. Despite a significant progress in the treatment of ARDS, our ability to identify early patients and predict outcomes remains limited. The development of novel biomarkers is crucial. In this study, we profiled microRNA (miRNA) expression of plasma-derived exosomes in ARDS disease by small RNA sequencing. Sequencing of 8 ARDS patients and 10 healthy subjects (HSs) allowed to identify 12 differentially expressed exosomal miRNAs (adjusted p < 0.05). Pathway analysis of their predicted targets revealed enrichment in several biological processes in agreement with ARDS pathophysiology, such as inflammation, immune cell activation, and fibrosis. By quantitative RT-PCR, we validated the alteration of nine exosomal miRNAs in an independent cohort of 15 ARDS patients and 20 HSs, among which seven present high capability in discriminating ARDS patients from HSs (area under the curve > 0.8) (miR-130a-3p, miR-221-3p, miR-24-3p, miR-98-3p, Let-7d-3p, miR-1273a, and miR-193a-5p). These findings highlight exosomal miRNA dysregulation in the plasma of ARDS patients which provide promising diagnostic biomarkers and open new perspectives for the development of therapeutics. [less ▲]

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See detailLong-term clinical follow-up of patients suffering from moderate-to-severe COVID-19 infection: a monocentric prospective observational cohort study.
Darcis, Gilles ULiege; Bouquegneau, Antoine ULiege; Maes, Nathalie ULiege et al

in International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases (2021), 109

OBJECTIVES: Various symptoms and considerable organ dysfunction persist following infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Uncertainty remains about the potential mid ... [more ▼]

OBJECTIVES: Various symptoms and considerable organ dysfunction persist following infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Uncertainty remains about the potential mid- and long-term health sequelae. This prospective study of patients hospitalized with coronavirus disease 2019 (COVID-19) in Liège University Hospital, Belgium aimed to determine the persistent consequences of COVID-19. METHODS: Patients admitted to the University Hospital of Liège with moderate-to-severe confirmed COVID-19, discharged between 2 March and 1 October 2020, were recruited prospectively. Follow-up at 3 and 6 months after hospital discharge included demographic and clinical data, biological data, pulmonary function tests (PFTs) and high-resolution computed tomography (CT) scans of the chest. RESULTS: In total, 199 individuals were included in the analysis. Most patients received oxygen supplementation (80.4%). Six months after discharge, 47% and 32% of patients still had exertional dyspnoea and fatigue. PFTs at 3-month follow-up revealed a reduced diffusion capacity of carbon monoxide (mean 71.6 ± 18.6%), and this increased significantly at 6-month follow-up (P<0.0001). Chest CT scans showed a high prevalence (68.9% of the cohort) of persistent abnormalities, mainly ground glass opacities. Duration of hospitalization, intensive care unit admission and mechanical ventilation were not associated with the persistence of symptoms 3 months after discharge. CONCLUSION: The prevalence of persistent symptoms following hospitalization with COVID-19 is high and stable for up to 6 months after discharge. However, biological, functional and iconographic abnormalities improved significantly over time. [less ▲]

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See detailA review in radiomics: Making personalized medicine a reality via routine imaging.
Guiot, Julien ULiege; Vaidyanathan, Akshayaa; DEPREZ, Louis ULiege et al

in Medicinal Research Reviews (2021)

Radiomics is the quantitative analysis of standard-of-care medical imaging; the information obtained can be applied within clinical decision support systems to create diagnostic, prognostic, and/or ... [more ▼]

Radiomics is the quantitative analysis of standard-of-care medical imaging; the information obtained can be applied within clinical decision support systems to create diagnostic, prognostic, and/or predictive models. Radiomics analysis can be performed by extracting hand-crafted radiomics features or via deep learning algorithms. Radiomics has evolved tremendously in the last decade, becoming a bridge between imaging and precision medicine. Radiomics exploits sophisticated image analysis tools coupled with statistical elaboration to extract the wealth of information hidden inside medical images, such as computed tomography (CT), magnetic resonance (MR), and/or Positron emission tomography (PET) scans, routinely performed in the everyday clinical practice. Many efforts have been devoted in recent years to the standardization and validation of radiomics approaches, to demonstrate their usefulness and robustness beyond any reasonable doubts. However, the booming of publications and commercial applications of radiomics approaches warrant caution and proper understanding of all the factors involved to avoid "scientific pollution" and overly enthusiastic claims by researchers and clinicians alike. For these reasons the present review aims to be a guidebook of sorts, describing the process of radiomics, its pitfalls, challenges, and opportunities, along with its ability to improve clinical decision-making, from oncology and respiratory medicine to pharmacological and genotyping studies. [less ▲]

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See detailAsthma and COPD Are Not Risk Factors for ICU Stay and Death in Case of SARS-CoV2 Infection
CALMES, Doriane ULiege; Graff, Sophie ULiege; MAES, Nathalie ULiege et al

in Journal of Allergy and Clinical Immunology: In Practice (2021), 9(1), 160-169

BACKGROUND: Asthmatics and patients with chronic obstructive pulmonary disease (COPD) have more severe outcomes with viral infections than people without obstructive disease. OBJECTIVE: To evaluate if ... [more ▼]

BACKGROUND: Asthmatics and patients with chronic obstructive pulmonary disease (COPD) have more severe outcomes with viral infections than people without obstructive disease. OBJECTIVE: To evaluate if obstructive diseases are risk factors for intensive care unit (ICU) stay and death due to coronavirus disease 2019 (COVID19). METHODS: We collected data from the electronic medical record from 596 adult patients hospitalized in University Hospital of Liege between March 18 and April 17, 2020, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We classified patients into 3 groups according to the underlying respiratory disease, present before the COVID19 pandemic. RESULTS: Among patients requiring hospitalization for COVID19, asthma and COPD accounted for 9.6% and 7.7%, respectively. The proportions of asthmatics, patients with COPD, and patients without obstructive airway disease hospitalized in the ICU were 17.5%, 19.6%, and 14%, respectively. One-third of patients with COPD died during hospitalization, whereas only 7.0% of asthmatics and 13.6% of patients without airway obstruction died due to SARS-CoV2. The multivariate analysis showed that asthma, COPD, inhaled corticosteroid treatment, and oral corticosteroid treatment were not independent risk factors for ICU admission or death. Male gender (odds ratio [OR]: 1.9; 95% confidence interval [CI]: 1.1-3.2) and obesity (OR: 8.5; 95% CI: 5.1-14.1) were predictors of ICU admission, whereas male gender (OR 1.9; 95% CI: 1.1-3.2), older age (OR: 1.9; 95% CI: 1.6-2.3), cardiopathy (OR: 1.8; 95% CI: 1.1-3.1), and immunosuppressive diseases (OR: 3.6; 95% CI: 1.5-8.4) were independent predictors of death. CONCLUSION: Asthma and COPD are not risk factors for ICU admission and death related to SARS-CoV2 infection. [less ▲]

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See detailCan predicting COVID-19 mortality in a European cohort using only demographic and comorbidity data surpass age-based prediction: An externally validated study.
Chatterjee, Avishek; Wu, Guangyao; Primakov, Sergey et al

in PLoS ONE (2021), 16(4), 0249920

OBJECTIVE: To establish whether one can build a mortality prediction model for COVID-19 patients based solely on demographics and comorbidity data that outperforms age alone. Such a model could be a ... [more ▼]

OBJECTIVE: To establish whether one can build a mortality prediction model for COVID-19 patients based solely on demographics and comorbidity data that outperforms age alone. Such a model could be a precursor to implementing smart lockdowns and vaccine distribution strategies. METHODS: The training cohort comprised 2337 COVID-19 inpatients from nine hospitals in The Netherlands. The clinical outcome was death within 21 days of being discharged. The features were derived from electronic health records collected during admission. Three feature selection methods were used: LASSO, univariate using a novel metric, and pairwise (age being half of each pair). 478 patients from Belgium were used to test the model. All modeling attempts were compared against an age-only model. RESULTS: In the training cohort, the mortality group's median age was 77 years (interquartile range = 70-83), higher than the non-mortality group (median = 65, IQR = 55-75). The incidence of former/active smokers, male gender, hypertension, diabetes, dementia, cancer, chronic obstructive pulmonary disease, chronic cardiac disease, chronic neurological disease, and chronic kidney disease was higher in the mortality group. All stated differences were statistically significant after Bonferroni correction. LASSO selected eight features, novel univariate chose five, and pairwise chose none. No model was able to surpass an age-only model in the external validation set, where age had an AUC of 0.85 and a balanced accuracy of 0.77. CONCLUSION: When applied to an external validation set, we found that an age-only mortality model outperformed all modeling attempts (curated on www.covid19risk.ai) using three feature selection methods on 22 demographic and comorbid features. [less ▲]

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See detailMapping the human genetic architecture of COVID-19 by worldwide meta-analysis
The COVID-19 Host Genetics Initiative; Gazon, Hélène; JUSZCZAK, Danusia ULiege et al

in Nature (2021)

The genetic makeup of an individual contributes to susceptibility and response to viral infection. While environmental, clinical and social factors play a role in exposure to SARS-CoV-2 and COVID-19 ... [more ▼]

The genetic makeup of an individual contributes to susceptibility and response to viral infection. While environmental, clinical and social factors play a role in exposure to SARS-CoV-2 and COVID-19 disease severity, host genetics may also be important. Identifying host-specific genetic factors indicate biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-COV-2 infection and COVID-19 severity. We describe the results of three genome-wide association meta-analyses comprising 49,562 COVID-19 patients from 46 studies across 19 countries worldwide. We reported 15 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases. They also represent potentially actionable mechanisms in response to infection. We further identified smoking and body mass index as causal risk factors for severe COVID-19. The identification of novel host genetic factors associated with COVID-19, with unprecedented speed, was enabled by prioritization of shared resources and analytical frameworks. This working model of international collaboration a blue-print for future genetic discoveries in the event of pandemics or for any complex human disease. [less ▲]

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See detailGC×GC-HRTOFMS for untargeted screening of exhaled breath
Stefanuto, Pierre-Hugues ULiege; Zanella, Delphine ULiege; Franchina, Flavio ULiege et al

Conference (2020, November)

In the galaxy of Omics Science, breathomics (i.e., exhaled breath analysis) knows an exponential growth. The full characterization of the breath composition and the understanding of the origin of these ... [more ▼]

In the galaxy of Omics Science, breathomics (i.e., exhaled breath analysis) knows an exponential growth. The full characterization of the breath composition and the understanding of the origin of these chemicals could have a gigantic impact for clinical research. Indeed, the potential of using non-invasive breath testing for patient status evaluation could be a game changer in disease monitoring and personalized medicine. Following that goal, there are numerous applications under development from cancer detection to diet adjustment. However, the complete characterization of the exhaled breath composition represents a complex analytical quest. From the exhaustive and reliable sampling, through robust untargeted analysis, to validated markers identification, the playground is large and require the development of new analytical workflows. To ensure the robustness of the entire process, every step must be carefully optimized and controlled with a robust QA/QC system. In order to resolve the complex composition of such samples, a powerful analytical technique is required. To obtain an untargeted screening of exhaled breath sample comprehensive two-dimensional gas chromatography coupled to mass spectrometry (GC×GC-MS) is a go to analytical solution. GC×GC-MS provides high separation resolution and orthogonal compounds identification metrics. Indeed, the retention times combined to the MS fragmentogram and potentially to the high-resolution MS provide strong identification confidence, which can reach level 2 MSI (metabolomics standard initiative) classification in a single analysis. The organic and biological analytical chemistry group (OBiAChem) from Liège University has been dedicating a lot of effort to tackle the challenges on the road of robust breath test. In this webinar, we will cover the different technological aspects of exhaled breath research including sampling, analysis, data processing, and QA/QC. In addition, we will cover some clinical applications and discuss the transferability of breath testing for large scale population screening. [less ▲]

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See detailNeutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19
Radermecker, Coraline ULiege; Detrembleur, Nancy ULiege; Guiot, Julien ULiege et al

in Journal of Experimental Medicine (2020), 217(12),

Infection with SARS-CoV-2 is causing a deadly and pandemic disease called coronavirus disease-19 (COVID-19). While SARS-CoV-2-triggered hyperinflammatory tissue-damaging and immunothrombotic responses are ... [more ▼]

Infection with SARS-CoV-2 is causing a deadly and pandemic disease called coronavirus disease-19 (COVID-19). While SARS-CoV-2-triggered hyperinflammatory tissue-damaging and immunothrombotic responses are thought to be major causes of respiratory failure and death, how they relate to lung immunopathological changes remains unclear. Neutrophil extracellular traps (NETs) can contribute to inflammation-associated lung damage, thrombosis, and fibrosis. However, whether NETs infiltrate particular compartments in severe COVID-19 lungs remains to be clarified. Here we analyzed postmortem lung specimens from four patients who succumbed to COVID-19 and four patients who died from a COVID-19-unrelated cause. We report the presence of NETs in the lungs of each COVID-19 patient. NETs were found in the airway compartment and neutrophil-rich inflammatory areas of the interstitium, while NET-prone primed neutrophils were present in arteriolar microthrombi. Our results support the hypothesis that NETs may represent drivers of severe pulmonary complications of COVID-19 and suggest that NET-targeting approaches could be considered for the treatment of uncontrolled tissue-damaging and thrombotic responses in COVID-19. © 2020 Radermecker et al. This article is distributed under the terms of an Attribution-Noncommercial-Share Alike-No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). [less ▲]

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See detailCould KL-6 levels in COVID-19 help to predict lung disease?
Frix, Anne-Noëlle ULiege; Schoneveld, Lauranne ULiege; LADANG, Aurélie ULiege et al

in Respiratory Research (2020), 21(309),

BACKGROUND: Coronavirus disease COVID-19 has become a public health emergency of international concern. Together with the quest for an effective treatment, the question of the post-infectious evolution of ... [more ▼]

BACKGROUND: Coronavirus disease COVID-19 has become a public health emergency of international concern. Together with the quest for an effective treatment, the question of the post-infectious evolution of affected patients in healing process remains uncertain. Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Its production is raised during epithelial lesions and cellular regeneration. In COVID-19 infection, KL-6 serum levels could therefore be of interest for diagnosis, prognosis and therapeutic response evaluation. MATERIALS AND METHODS: Our study retrospectively compared KL-6 levels between a cohort of 83 COVID-19 infected patients and two other groups: healthy subjects (n = 70) on one hand, and a heterogenous group of patients suffering from interstitial lung diseases (n = 31; composed of 16 IPF, 4 sarcoidosis, 11 others) on the other hand. Demographical, clinical and laboratory indexes were collected. Our study aims to compare KL-6 levels between a COVID-19 population and healthy subjects or patients suffering from interstitial lung diseases (ILDs). Ultimately, we ought to determine whether KL-6 could be a marker of disease severity and bad prognosis. RESULTS: Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects, but to a lesser extent than in patients suffering from ILD. Increased levels of KL-6 in COVID-19 patients were associated with a more severe lung disease. DISCUSSION AND CONCLUSION: Our results suggest that KL-6 could be a good biomarker to assess ILD severity in COVID-19 infection. Concerning the therapeutic response prediction, more studies are necessary. [less ▲]

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