Publications of Michel Moutschen
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See detailFrailty but not sarcopenia nor malnutrition increases the risk of developing COVID-19 in older community-dwelling adults.
Lengele, Laetitia ULiege; Locquet, Médéa ULiege; Moutschen, Michel ULiege et al

in Aging clinical and experimental research (in press)

BACKGROUND: The identification of coronavirus disease 2019 (COVID-19) risk factors is requested to implement prevention strategies. AIM: To explore the associations between the COVID-19 incidence and ... [more ▼]

BACKGROUND: The identification of coronavirus disease 2019 (COVID-19) risk factors is requested to implement prevention strategies. AIM: To explore the associations between the COVID-19 incidence and malnutrition, sarcopenia, and frailty, identified as potential risk factors in previous cross-sectional studies. METHODS: Malnutrition, sarcopenia, and frailty were assessed at the last available follow-up from the Sarcopenia and Physical Impairments with Advancing Age (SarcoPhAge) cohort (i.e., the fifth year that ended in 2019) according to the Mini-Nutritional Assessment short-form, the European Working Group on Sarcopenia in Older People (EWGSOP2), and the Fried criteria, respectively. Information regarding the COVID-19 was gathered by phone calls interviews in April 2021 to measure its self-declared incidence. Adjusted Cox regressions and Kaplan-Meier curves were performed. RESULTS: The present study included 241 participants [median age 75.6 (73.0-80.6) years, 63.1% women]. Among them, 27 participants (11.2%) developed the non-fatal Covid-19. No significant increased risks of COVID-19 were observed in patients with malnutrition [adjusted HR 1.14 (0.26-5.07)] and sarcopenia [adjusted HR 1.25 (0.35-4.42)]. Nevertheless, the incidence of COVID-19 was significantly higher in frail (44.4%) than in robust participants (8.5%) [Adjusted HR 7.01 (2.69-18.25)], which was confirmed by the Kaplan-Meier curves (p < 0.001). Among the frailty syndrome components, a low physical activity level was the only one significantly associated with an increased risk of COVID-19 [adjusted HR 5.18 (1.37-19.54)]. CONCLUSION: Despite some limitations in the methodology of this study (i.e., limited sample size, COVID-19 incidence self-reported and not assessed systematically using objective measurements) requiring careful  consideration, an increased risk to develop COVID-19 was observed in the presence of the frailty syndrome. Further investigations are needed to elaborate on our findings. [less ▲]

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See detailKinetics and persistence of the cellular and humoral immune responses to BNT162b2 mRNA vaccine in SARS-CoV-2-naive and -experienced subjects
Desmecht, Salomé ULiege; Tashkeev, Aleksandr ULiege; Nicole Marechal, Nicole et al

E-print/Working paper (2022)

Background: Understanding and measuring the individual level of immune protection and its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination is mandatory for the management of ... [more ▼]

Background: Understanding and measuring the individual level of immune protection and its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination is mandatory for the management of the vaccination booster campaign. Our prospective study was designed to assess the immunogenicity of the BNT162b2 mRNA vaccine in triggering the humoral and the cellular immune response in healthcare workers up to 6 months after two doses vaccination. Methods: This prospective study enrolled 208 healthcare workers from the Liège University Hospital (CHU) of Liège in Belgium. All participants received two doses of BioNTech/Pfizer COVID-19 vaccine (BNT162b2). Fifty participants were SARS-CoV-2 experienced (self-reported SARS-CoV-2 infection) and 158 were naïve (no reported SARS-CoV-2 infection) before the vaccination. Blood sampling was performed at the day of the first (T0) and second (T1) vaccine doses administration, then at 2 weeks (T2), 4 weeks (T3) and 6 months (T4) after the 1st vaccine dose administration. A total of 1024 blood samples were collected. All samples were tested for the presence of anti-Spike antibodies using DiaSorin LIAISON SARS-CoV-2 TrimericS IgG assay. Neutralizing antibodies against the SARS-CoV-2 Wuhan-like variant strain were quantified in all samples using a Vero E6 cell-based neutralization-based assay. Cell-mediated immune response was evaluated at T4 on 80 participants by measuring the secretion of IFN- on peripheral blood lymphocytes using the QuantiFERON Human IFN- SARS-CoV-2, Qiagen. All participants were monitored on weekly-basis for the novo SARS-COV-2 infection for 4 weeks after the 1st vaccine dose administration. We analyzed separately the naïve and experienced participants. Findings: We found that anti-spike antibodies and neutralization capacity levels were significantly higher in SARS-CoV-2 experienced healthcare workers (HCWs) compared to naïve HCWs at all time points analyzed. Cellular immune response was similar in the two groups six months following 2nd dose of the vaccine. Reassuringly, most participants had a detectable cellular immune response to SARS-CoV-2 six months after vaccination. Besides the impact of SARS-CoV-2 infection history on immune response to BNT162b2 mRNA vaccine, we observed a significant negative correlation between age and persistence of humoral response. Cellular immune response was, however, not significantly correlated to age, although a trend towards a negative impact of age was observed. Conclusions: Our data strengthen previous findings demonstrating that immunization through vaccination combined with natural infection is better than 2 vaccine doses immunization or natural infection alone. It may have implications for personalizing mRNA vaccination regimens used to prevent severe COVID-19 and reduce the impact of the pandemic on the healthcare system. More specifically, it may help prioritizing vaccination, including for the deployment of booster doses. [less ▲]

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See detailImpact of the COVID-19 pandemic situation on HIV care in Liège, Belgium
El Moussaoui, Majdouline ULiege; Lambert, Nicolas ULiege; MAES, Nathalie ULiege et al

Poster (2021, November 30)

Background: The COVID-19 pandemic and associated containment measures dramatically affected the health care systems including the screening of human immunodeficiency virus and the management of people ... [more ▼]

Background: The COVID-19 pandemic and associated containment measures dramatically affected the health care systems including the screening of human immunodeficiency virus and the management of people living with HIV around the world by making the access to preventive care services and specific medical monitoring more difficult. Objective: To study the impact of the COVID-19 pandemic on the holistic care of people living with HIV in Liège (Belgium). Methods: In this retrospective observational study conducted in Liège University Hospital, we compared the out-patient follow-up of HIV-infected individuals as well as the number of new HIV diagnoses between 2019 and 2020 and between the different waves of the COVID-19 pandemic in 2020. Results: In 2020, when compared to 2019, we observed a significant decrease in the number of new HIV diagnoses, especially during the first wave of the pandemic, and in the number of consultations undertaken by sexual health services, psychologists and specialists in infectious diseases at our HIV clinic. We also observed a decrease in the number of viral load assays and blood CD4+ T-cells count analyses performed, although we found less patients with HIV plasma viral load above 400 copies per mL in 2020. Finally, we noted a significant reduction in terms of screening of our HIV-infected patients for hepatitis C, syphilis, colorectal and anal cancers and hypercholesterolemia. Conclusions: Our experience exhibits the deleterious impact of the COVID-19 pandemic on the HIV care and the need to implement new strategies to guarantee its continuum. [less ▲]

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See detail"Opter pour l'obligation vaccinale est un choix de société"
Muraille, Eric; De Kerchove d'Exaerde, Alban; Drion, Pierre ULiege et al

Article for general public (2021)

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See detailComparison of clinical and biological characteristics of HIV infected patients presenting Cryptococcus neorformans versus C. curvatus /C. laurentii meningitis
Zono, Bive ULiege; MOUTSCHEN, Michel ULiege; SITUAKIBANZA, Hippolyte et al

in BMC Infectious Diseases (2021), 21(1), 1-10

Background: Cryptococcal meningitis is mainly caused by Cryptococcus neoformans/C. gattii complex. We compared the clinical, biological, and antifungal susceptibility profiles of isolates from ... [more ▼]

Background: Cryptococcal meningitis is mainly caused by Cryptococcus neoformans/C. gattii complex. We compared the clinical, biological, and antifungal susceptibility profiles of isolates from HIV‑Infected Patients (HIVIP) with C. neoformans (Cn) versus C. curvatus/C. laurentii (Cc/Cl) meningitis. Methods: Comparative analytical study were conducted. Apart from patients’ clinical data, the following analysis were performed and the results were compared in both groups: biochemical examination, cryptococcal antigen test, India ink staining, and culture on Cerebral Spinal Fluid (CSF), strains identification by mass spectrometry, ITS sequencing, PCR serotyping and antifungal susceptibility. The main outcome variable was the “species of Cryptococcus identified”, which was compared to other variables of the same type using the Pearson Chi‑square test or the Fisher exact test. Results: A total of 23 (79.3%) Cn meningitis cases versus 6 (20.7%) Cc/Cl meningitis were retained. Cn meningitis was more frequently associated with headache (100% vs 50%, p = 0.005) than Cc/Cl meningitis and meningeal signs were more frequent in Cn infected patients. Biologically, hypoglycorrhachia and low CD4 count were more observed in Cn group (90% vs 20% of patients, p = 0.01; 45.6 vs 129.8 cells/µL, p = 0.02, respectively). A higher proportion of Cn strains (91.3%) showed a low Minimum Inhibitory Concentration (MIC) (< 8 mg/L) for fluconazole compared to Cc/Cl strains (66.7%). Also, Cc/Cl strains resistant to 5‑flucytosine and amphotericin B were found in 16.7% of cases for each of the two antifungal agents. Cryptococcus detection by routine analysis (India ink, culture, and antigens) was better for Cn samples than Cc/Cl. Except ITS sequencing, which identified all strains of both groups, mass spectrometry and serotyping PCR identified Cn strains better than Cc/Cl (100% vs 80%, p = 0.1; 100% vs 0%, p < 0.0001, respectively). After treatment with amphotericin B, 5‑flucytosine, and fluconazole in both groups, the outcome was similar. Conclusions: Clinical presentation of Cn meningitis is certainly more severe than that of Cc/Cl meningitis, but Cc/ Cl infection should be considered in the management of HIVIP with meningeal syndrome because of the diagnostic difficulty and the high MICs of antifungal agents required for the treatment of meningitis due to these cryptococcal species. [less ▲]

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See detailMolecular Analysis of Cryptococcus spp. Reveals Species Diversity and Multilocus Sequence Typing Heterogeneity among People Living with HIV in Kinshasa
Zono, Bive ULiege; SACHELI, Rosalie ULiege; Situakibanza, Hippolyte et al

in Journal of Fungi (2021, October 28), 7(916), 42-43

Objectives: In the Democratic Republic of Congo (DRC), the neuromeningeal cryptococcosis (NMC) hospital prevalence varies between 8.8 and 11% with a death rate of about 50%. However, the Cryptococcus ... [more ▼]

Objectives: In the Democratic Republic of Congo (DRC), the neuromeningeal cryptococcosis (NMC) hospital prevalence varies between 8.8 and 11% with a death rate of about 50%. However, the Cryptococcus isolates circulating are poorly and formerly described. We describe the molecular characterization of Cryptococcus spp. isolated from people living with HIV (PLWHIV), and the association between NMC severity factors and the Cryptococcus multilocus sequence typing (MLST) profiles. Materials & Methods: Cerebral spinal fluid (CSF) was collected from PLWHIV with neuromeningeal syndrome hospitalized in three Kinshasa public hospitals from 1 February 2019 to 29 February 2020, and cultured on Sabouraud dextrose agar + chloramphenicol medium afterwards. Serotyping PCR, internal transcribed spacer (ITS) sequencing, and MLST from next-generation sequencing (NGS) data were performed to genotype the Cryptococcus isolates. Raw NGS data were processed and the loci alleles were manually extracted using Geneious software. NMC severity factors such as hypoglycorrhachia (<50 mg/dL), raised CSF opening pressure (>30 cm water), and the patient pejorative outcome were compared to the Cryptococcus sequence type (ST)-MLST profile which was identified, using Pearson chi-square test or Fisher exact test. Results: Out of 29 isolates included in the present study, 23 (79.3%; 95% IC: 65.5–93.1) have been identified as serotype A using serotyping PCR, while 6 (20.7%; 95% IC: 6.9–34.5) had unidentifiable profile. Moreover, all the 29 isolates have been characterized by ITS sequencing as follow: Cryptococcus neoformans var. grubii (23 of 29 isolates, 79.3%), Cryptococcus curvatus (5 of 29, 17.2%), and Cryptococcus laurentii (1 of 29, 3.5%). Apart from this highlighted species diversity, C. neoformans var. grubii isolates were all identified as molecular type VNI using the MLST ISHAM scheme, with seven different STs including ST93 (14 out of 23, 60.9%), ST53 (1 out of 23, 4.3%), ST31 (1 out of 23, 4.3%), ST5 (1 out of 23, 4.3%), ST4 (1 out of 23, 4.3%), ST69 (1 out 23, 4.3%), and one novel ST not yet reported worldwide (2 out of 23, 8.6%). Furthermore, two isolates (8.6%) showed a mixed molecular profile (under investigation). Phylogenetic analysis carried out by the unweighted pair group method with arithmetic mean algorithm (UPGMA) of concatenated gene sequences from the seven MLST loci indicated that the main ST isolated in this study is very close to the only isolate previously reported from the DRC. The others are distant from it, even more so for ST69. All the STs identified in the present study have been isolated in the neighbouring countries of the DRC except for ST53, which has only been reported in Southeast Asia. Among NMC severity factors, only the patient pejorative outcome was associated with the minority STs infections (87.5%, p = 0.02) (ST53, ST31, ST5, ST4, STA, ST69). Conclusions: Molecular analysis of Cryptococcus spp. isolates showed wide species diversity, and ST-MLST heterogenicity within the only one molecular type identified. The existence of the STs isolated in this study in the DRC neighbouring countries suggests probable close-to-home spread. Furthermore, infections due to minority STs were associated with a pejorative outcome than those due to ST93. [less ▲]

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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 detailImpact of the COVID-19 pandemic situation on HIV care in Liège, Belgium
El Moussaoui, Majdouline ULiege; Lambert, Nicolas ULiege; MAES, Nathalie ULiege et al

in HIV Research & Clinical Practice (2021)

Background: The COVID-19 pandemic and associated containment measures dramatically affected the health care systems including the screening of human immunodeficiency virus and the management people living ... [more ▼]

Background: The COVID-19 pandemic and associated containment measures dramatically affected the health care systems including the screening of human immunodeficiency virus and the management people living with HIV around the world by making the access to preventive care services and specific medical monitoring more difficult. Objective: To study the impact of the COVID-19 pandemic on the holistic care of people living with HIV in Liège (Belgium). Methods: In this retrospective observational study conducted in Liège University Hospital, we compared the out-patient follow-up of HIV-infected individuals as well as the number of new HIV diagnoses between 2019 and 2020 and between the different waves of the COVID-19 pandemic in 2020. Results: In 2020, when compared to 2019, we observed a significant decrease in the number of new HIV diagnoses, especially during the first wave of the pandemic, and in the number of consultations undertaken by sexual health services, psychologists and specialists in infectious diseases at our HIV clinic. We also observed a decrease in the number of viral load assays and blood CD4 + T-cells count analyses performed, although we found less patients with HIV plasma viral load above 400 copies per mL in 2020. Finally, we noted a significant reduction in terms of screening of our HIV-infected patients for hepatitis C, syphilis, colorectal and anal cancers and hypercholesterolemia. Conclusions: Our experience exhibits the deleterious impact of the COVID-19 pandemic on the HIV care and the need to implement new strategies to guarantee its continuum. [less ▲]

Detailed reference viewed: 158 (90 ULiège)
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See detailComparison of clinical and biological characteristics of HIV infected patients presenting Cryptococcus neorformans versus C. curvatus /C. laurentii meningitis
Zono, Bive ULiege; MOUTSCHEN, Michel ULiege; Situakibanza, Hippolyte et al

Poster (2021, June 12)

Clinical presentation of Cn meningitis is certainly more severe than that of Cc/Cl meningitis, but Cc/Cl infection should be considered in the management of HIVIP with meningeal syndrome because of the ... [more ▼]

Clinical presentation of Cn meningitis is certainly more severe than that of Cc/Cl meningitis, but Cc/Cl infection should be considered in the management of HIVIP with meningeal syndrome because of the diagnostic difficulty and the high MICs of antifungal agents required for the treatment of meningitis due to these cryptococcal species. [less ▲]

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See detailLung and liver sarcoidosis‐like reaction induced by tocilizumab
Lambert, Nicolas ULiege; Hansen, Isabelle ULiege; El Moussaoui, Majdouline ULiege et al

in British Journal of Clinical Pharmacology (2021)

A drug‐induced sarcoidosis‐like reaction is a systemic granulomatous reaction indistinguishable from sarcoidosis and occurring in temporal relationship with a drug initiation. In this article, we report a ... [more ▼]

A drug‐induced sarcoidosis‐like reaction is a systemic granulomatous reaction indistinguishable from sarcoidosis and occurring in temporal relationship with a drug initiation. In this article, we report a patient who developed lung and liver granulomatous lesions following tocilizumab initiation for a giant cell arteritis. Infectious, toxic, neoplastic and inflammatory differential diagnoses were ruled out and lesions regressed after treatment cessation, leading to the diagnosis of tocilizumab induced sarcoidosis‐like reaction. We review the six cases reported so far and emphasize the value of a prompt diagnosis. Finally, we discuss the potential pathophysiological mechanisms underlying this rare reaction, which could help to better understand the pathophysiology of sarcoidosis. [less ▲]

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See detailImmunosuppression Withdrawal After Liver Transplantation for Common Variable Immunodeficiency.
Detry, Olivier ULiege; MEURISSE, Nicolas ULiege; Jouret, François ULiege et al

in Liver Transplantation (2021), 27(3), 456-458

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See detailIn-Depth Longitudinal Comparison of Clinical Specimens to Detect SARS-CoV-2.
Defêche, Justine ULiege; AZARZAR, Samira ULiege; Mesdagh, Alyssia ULiege et al

in Pathogens (Basel, Switzerland) (2021), 10(11),

The testing and isolation of patients with coronavirus disease 2019 (COVID-19) are indispensable tools to control the ongoing COVID-19 pandemic. PCR tests are considered the "gold standard" of COVID-19 ... [more ▼]

The testing and isolation of patients with coronavirus disease 2019 (COVID-19) are indispensable tools to control the ongoing COVID-19 pandemic. PCR tests are considered the "gold standard" of COVID-19 testing and mostly involve testing nasopharyngeal swab specimens. Our study aimed to compare the sensitivity of tests for various sample specimens. Seventy-five participants with confirmed COVID-19 were included in the study. Nasopharyngeal swabs, oropharyngeal swabs, Oracol-collected saliva, throat washes and rectal specimens were collected along with pooled swabs. Participants were asked to complete a questionnaire to correlate specific clinical symptoms and the symptom duration with the sensitivity of detecting COVID-19 in various sample specimens. Sampling was repeated after 7 to 10 days (T2), then after 14 to 20 days (T3) to perform a longitudinal analysis of sample specimen sensitivity. At the first time point, the highest percentages of SARS-CoV-2-positive samples were observed for nasopharyngeal samples (84.3%), while 74%, 68.2%, 58.8% and 3.5% of throat washing, Oracol-collected saliva, oropharyngeal and rectal samples tested positive, respectively. The sensitivity of all sampling methods except throat wash samples decreased rapidly at later time points compared to the first collection. The throat washing method exhibited better performance than the gold standard nasopharyngeal swab at the second and third time points after the first positive test date. Nasopharyngeal swabs were the most sensitive specimens for early detection after symptom onset. Throat washing is a sensitive alternative method. It was found that SARS-CoV-2 persists longer in the throat and saliva than in the nasopharynx. [less ▲]

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See detailImpact of switch from tenofovir disoproxil fumarate-based regimens to tenofovir alafenamide-based regimens on lipid profile, weight gain and cardiovascular risk score in people living with HIV.
Plum, Pierre-Emmanuel; Maes, Nathalie ULiege; Sauvage, Anne-Sophie ULiege et al

in BMC Infectious Diseases (2021), 21(1), 910

BACKGROUND: As cardiovascular diseases represent the main cause of non-AIDS related death in people living with HIV (PLWH) with undetectable viral load, we evaluated lipid profile, weight gain and ... [more ▼]

BACKGROUND: As cardiovascular diseases represent the main cause of non-AIDS related death in people living with HIV (PLWH) with undetectable viral load, we evaluated lipid profile, weight gain and calculated cardiovascular risk change after switching from tenofovir disoproxil fumarate (TDF)-based regimens to tenofovir alafenamide (TAF)-based regimens. METHODS: For this retrospective study, we selected HIV-infected patients with suppressed viral load who fitted in one of the two groups below: First group (TDF/TDF): Patients treated continuously with TDF-based regimens. Second group (TDF/TAF): Patients treated with TDF-regimens during at least 6 months then switched to TAF-regimens while maintaining other drugs unchanged. Available data included date of birth, gender, ethnicity, lymphocyte T CD4(+) count, weight, height, blood pressure, current/ex/non-smoker, diabetes mellitus, familial cardiovascular event, lipid profile, duration and nature of antiretroviral therapy. Lipid parameters, weight and calculated cardiovascular risk using 5-year reduced DAD score algorithm [Friis-Møller et al. in Eur J Cardiovasc Prev Rehabil 17:491-501, 2010] were analyzed in each groups. RESULTS: Switching from TDF to TAF resulted in a significant increase in triglycerides levels, total cholesterol and HDL cholesterol. LDL cholesterol and total cholesterol/HDL ratio did not show significant changes. Calculated cardiovascular risk increased after switch from TDF- to TAF-based therapy. CONCLUSIONS: Together with favorable outcomes at the bone and kidney levels, potential negative impact of TAF on lipid profile should be included in the reflection to propose the most appropriate and tailored ARV treatment. [less ▲]

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See detailDual‑specificity phosphatase 3 deletion promotes obesity, non‑alcoholic steatohepatitis and hepatocellular carcinoma
Jacques, Sophie ULiege; Arjomand, Arash ULiege; Perée, Hélène ULiege et al

in Scientific Reports (2021), 11

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic pathology in Western countries. It encompasses a spectrum of conditions ranging from simple steatosis to more severe and ... [more ▼]

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic pathology in Western countries. It encompasses a spectrum of conditions ranging from simple steatosis to more severe and progressive non-alcoholic steatohepatitis (NASH) that can lead to hepatocellular carcinoma (HCC). Obesity and related metabolic syndrome are important risk factors for the development of NAFLD, NASH and HCC. DUSP3 is a small dual-specificity protein phosphatase with a poorly known physiological function. We investigated its role in metabolic syndrome manifestations and in HCC using a mouse knockout (KO) model. While aging, DUSP3-KO mice became obese, exhibited insulin resistance, NAFLD and associated liver damage. These phenotypes were exacerbated under high fat diet (HFD). In addition, DEN administration combined to HFD led to rapid HCC development in DUSP3-KO compared to wild type (WT) mice. DUSP3-KO mice had more serum triglycerides, cholesterol, AST and ALT compared to control WT mice under both regular chow diet (CD) and HFD. The level of fasting insulin was higher compared to WT mice, though, fasting glucose as well as glucose tolerance were normal. At the molecular level, HFD led to decreased expression of DUSP3 in WT mice. DUSP3 deletion was associated with increased and consistent phosphorylation of the insulin receptor (IR) and with higher activation of the downstream signaling pathway. In conclusion, our results support a new role for DUSP3 in obesity, insulin resistance, NAFLD and liver damage. [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 detailProgressive phasing out of baseline CD4+ cell count testing for people living with HIV in Kinshasa, Democratic Republic of the Congo.
Ngongo, Nadine Mayasi; Nani-Tuma, Hippolyte Situakibanza; Mambimbi, Marcel Mbula et al

in AIDS (London, England) (2021), 35(5), 841-843

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See detailTransmission of SARS-CoV-2 After COVID-19 Screening and Mitigation Measures for Primary School Children Attending School in Liège, Belgium.
Meuris, Christelle ULiege; Kremer, Cécile; Geerinck, Anton ULiege et al

in JAMA Network Open (2021), 4(10), 2128757

IMPORTANCE: Recent data suggest a relatively low incidence of COVID-19 among children. The possible role that children attending primary school may play in the transmission of SARS-CoV-2 remains poorly ... [more ▼]

IMPORTANCE: Recent data suggest a relatively low incidence of COVID-19 among children. The possible role that children attending primary school may play in the transmission of SARS-CoV-2 remains poorly understood. OBJECTIVE: To gain a better understanding of the possible role of children in the transmission of SARS-CoV-2. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted from September 21 to December 31, 2020, in a primary school in Liège, Belgium, among a volunteer sample of 181 children, parents, and school employees. EXPOSURES: Participants were tested for SARS-CoV-2 infection once a week for 15 weeks through throat washing, performed with 5 mL of saline and collected in a sterile tube after approximately 30 seconds of gargling. Quantitative reverse transcription-polymerase chain reaction was performed to detect SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: In case of test positivity, participants were asked to complete a questionnaire aimed at determining the timing of symptom onset and symptom duration. SARS-CoV-2 genetic sequencing was also performed. Confirmed cases were linked based on available information on known contacts and viral sequences. RESULTS: A total of 181 individuals participated in this study, including 63 children (34 girls [54.0%]; mean [SD] age, 8.6 [1.9] years [range, 5-13 years]) and 118 adults (75 women [63.6%]; mean [SD] age, 42.5 [5.7] years [range, 30-59 years]). Forty-five individuals (24.9%) tested positive: 13 children (20.6%; 95% CI, 10.6%-30.6%) and 32 adults (27.1%; 95% CI, 19.1%-35.7%) (P = .34). Children were more often asymptomatic compared with adults (6 [46.2%; 95% CI, 19.1%-73.3%] vs 4 of 31 [12.9%; 95% CI, 1.3%-24.5%]; P = .04). The median duration of symptoms was shorter in children than in adults (0.00 days [IQR, 0.00-1.00 days] vs 15.00 days [IQR, 7.00-22.00 days]). A reconstruction of the outbreak revealed that most transmission events occurred between teachers and between children within the school. Of the observed household transmission events, most seemed to have originated from a child or teacher who acquired the infection at school. CONCLUSIONS AND RELEVANCE: Despite the implementation of several mitigation measures, the incidence of COVID-19 among children attending primary school in this study was comparable to that observed among teachers and parents. Transmission tree reconstruction suggests that most transmission events originated from within the school. Additional measures should be considered to reduce the transmission of SARS-CoV-2 at school, including intensified testing. [less ▲]

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See detailDecrease in late presentation for HIV care in Kinshasa, DRC, 2006-2020.
Ngongo, Nadine Mayasi; Nani-Tuma, Hippolyte Situakibanza; Mambimbi, Marcel Mbula et al

in AIDS research and therapy (2021), 18(1), 41

INTRODUCTION: Late presentation for HIV care is a well-described issue for the success of ART outcomes and the cause of higher morbidity, mortality and further transmission. Monitoring the level of late ... [more ▼]

INTRODUCTION: Late presentation for HIV care is a well-described issue for the success of ART outcomes and the cause of higher morbidity, mortality and further transmission. Monitoring the level of late presentation and understanding the factors associated with it would help to tailor screening and information strategies for better efficiency. We performed a retrospective cohort study in Kinshasa, the capital of the DRC. The studied population included HIV-positive adults newly enrolled in HIV care between January 2006 and June 2020 at 25 HIV urban care facilities. Patient information collected at presentation for HIV care included age, sex, WHO clinical stage and screening context. We used 2 definitions of late presentation: the WHO definition of advanced HIV disease (WHO stage 3/4 or CD4 cell count < 200 cells/mm(3)) and a more inclusive definition (WHO stage 3/4 or CD4 cell count < 350 cells/mm(3)). RESULTS: A total of 10,137 HIV-infected individuals were included in the analysis. The median age was 40 years; 68% were female. A total of 45.9% or 47.5% of the patients were late presenters, depending on the definition used. The percentage of patients with late presentation (defined as WHO stage 3/4 or CD4 cell count < 350 cells/mm(3)) decreased during recent years, from 70.7% in 2013 to 46.5% in 2017 and 23.4% in 2020. Age was associated with a significantly higher risk of LP (p < 0.0001). We did not observe any impact of sex. CONCLUSIONS: The frequency of late presentation for care is decreasing in Kinshasa, DRC. Efforts have to be continued. In particular, the issue of late diagnosis in older individuals should be addressed. [less ▲]

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See detailLongitudinal analysis of sociodemographic, clinical and therapeutic factors of HIV-infected individuals in Kinshasa at antiretroviral therapy initiation during 2006-2017.
Ngongo, Nadine Mayasi; Darcis, Gilles ULiege; Nanituna, Hippolyte Situakibanza et al

in PLoS ONE (2021), 16(11), 0259073

BACKGROUND: The benefits of antiretroviral therapy (ART) underpin the recommendations for the early detection of HIV infection and ART initiation. Late initiation (LI) of antiretroviral therapy ... [more ▼]

BACKGROUND: The benefits of antiretroviral therapy (ART) underpin the recommendations for the early detection of HIV infection and ART initiation. Late initiation (LI) of antiretroviral therapy compromises the benefits of ART both individually and in the community. Indeed, it promotes the transmission of infection and higher HIV-related morbidity and mortality with complicated and costly clinical management. This study aims to analyze the evolutionary trends in the median CD4 count, the median time to initiation of ART, the proportion of patients with advanced HIV disease at the initiation of ART between 2006 and 2017 and their factors. METHODS AND FINDINGS: HIV-positive adults (≥ 16 years old) who initiated ART between January 1, 2006 and December 31, 2017 in 25 HIV care facilities in Kinshasa, the capital of DRC, were eligible. The data were processed anonymously. LI is defined as CD4≤350 cells/μl and/or WHO clinical stage III or IV and advanced HIV disease (AHD), as CD4≤200 cells/μl and/or stage WHO clinic IV. Factors associated with advanced HIV disease at ART initiation were analyzed, irrespective of year of enrollment in HIV care, using logistic regression models. A total of 7278 patients (55% admitted after 2013) with an average age of 40.9 years were included. The majority were composed of women (71%), highly educated women (68%) and married or widowed women (61%). The median CD4 was 213 cells/μl, 76.7% of patients had CD4≤350 cells/μl, 46.1% had CD4≤200 cells/μl, and 59% of patients were at WHO clinical stages 3 or 4. Men had a more advanced clinical stage (p <0.046) and immunosuppression (p<0.0007) than women. Overall, 70% of patients started ART late, and 25% had AHD. Between 2006 and 2017, the median CD4 count increased from 190 cells/μl to 331 cells/μl (p<0.0001), and the proportions of patients with LI and AHD decreased from 76% to 47% (p< 0.0001) and from 18.7% to 8.9% (p<0.0001), respectively. The median time to initiation of ART after screening for HIV infection decreased from 40 to zero months (p<0.0001), and the proportion of time to initiation of ART in the month increased from 39 to 93.3% (p<0.0001) in the same period. The probability of LI of ART was higher in married couples (OR: 1.7; 95% CI: 1.3-2.3) (p<0.0007) and lower in patients with higher education (OR: 0.74; 95% CI: 0.64-0.86) (p<0.0001). CONCLUSION: Despite increasingly rapid treatment, the proportions of LI and AHD remain high. New approaches to early detection, the first condition for early ART and a key to ending the HIV epidemic, such as home and work HIV testing, HIV self-testing and screening at the point of service, must be implemented. [less ▲]

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