[When eosinophilia is not only a marker of asthma ]. / Cas clinique. Quand l'éosinophilie n'est pas qu'un marqueur d'asthme...

We report the case of a patient who has been hospitalized for dyspnea. Investigations revealed airway obstruction, eosinophilia, elevated IgE and elevated exhaled nitric oxide. Patient improved with oral corticosteroids (OCS). However, the patient presented two exacerbations requiring OCS during the next twelve months. Chest CT scan revealed two multiloculated parenchymal lesions. Lab test was positive for Echinococcus and Western-Blot confirmed infection with Echinococcus granulosus. Bronchoalveolar lavage confirmed the presence of 6 % eosinophils. Echinococcus granulosis is a zoonotic larval infection caused by a tapeworm larva. Patients with this disease may be asymptomatic for years. Early identification and management, in a multidisciplinary team, are essential and rely mainly on surgical intervention and antiparasitic treatments. This article presents the case of a young patient with pulmonary echinococcosis.

Nous rapportons le cas d'un patient ayant été hospitalisé dans un contexte d'obstruction bronchique, avec une légère éosinophilie, une élévation des IgE et du monoxyde d'azote dans l'air exhalé, qui a évolué favorablement sous corticostéroïdes oraux (CSO). L'évolution est marquée par deux exacerbations d'asthme d'évolution favorable sous CSO dans les douze mois de suivi. Une tomodensitométrie thoracique révèle la présence de deux lésions pulmonaires kystiques. Les sérologies infectieuses mettent en évidence une positivité pour l'espèce -Echinococcus et une confirmation pour l'Echinococcus granulosus. Le lavage broncho-alvéolaire retrouve une hyperéosinophilie à 6 %. L'échinococcose kystique est une infection larvaire zoonotique causée par une larve de taenia. Les patients atteints de cette maladie peuvent être asymptomatiques pendant de nombreuses années. Une identification précoce et une prise en charge adéquate, en équipe pluridisciplinaire, sont primordiales et reposent essentiellement sur une intervention chirurgicale et des traitements anti-parasitaires. Cet article présente le cas d'un jeune patient atteint d'une échinococcose kystique pulmonaire.

Risk Factors for Late HIV Presentation in Patients Treated at a Single Belgian Reference Centre from 2018 to 2022.

A late HIV diagnosis is associated with increased mortality and morbidity, increased healthcare costs and increased onward viral transmission. In this regard, we retrospectively analysed the characteristics of patients who presented for care at our centre from January 2018 to December 2022 to assess the proportion of patients and factors associated with late HIV presentation. We collected data from the Liège University Hospital database, and we used binary logistic regression models to analyse the impact of individuals' characteristics on late presentation. Among 167 participants, 38.3% were late presenters (LPs) (presenting for care with a CD4+ T-cell count < 350 cells/mm3 or after an AIDS-defining event), and 21.6% were late presenters with advanced disease (LPs-AD) (presenting for care with a CD4+ T-cell count < 200 cells/mm3 or after an AIDS-defining event). The risk of being an LPs-AD was increased in older individuals (OR on log-transformed age: 7.5) and individuals of sub-Saharan African origin compared to individuals of Belgian or other origin (ORs of 0.30 and 0.25, respectively). The results of this study suggest that broadening the focus beyond the previously common risk groups is essential to prevent late diagnosis.

Cluster Analysis Identifies Distinct Patterns of T-Cell and Humoral Immune Responses Evolution Following a Third Dose of SARS-CoV-2 Vaccine in People Living with HIV.

(1) Background: Many vaccines require higher, additional doses or adjuvants to provide adequate protection for people living with HIV (PLWH). Despite their potential risk of severe coronavirus disease 2019, immunological data remain sparse, and a clear consensus for the best booster strategy is lacking. (2) Methods: Using the data obtained from our previous study assessing prospective T-cell and humoral immune responses before and after administration of a third dose of SARS-CoV-2 vaccine, we assessed the correlations between immune parameters reflecting humoral and cellular immune responses. We further aimed at identifying distinct clusters of patients with similar patterns of immune response evolution to determine how these relate to demographic and clinical factors. (3) Results: Among 80 PLWH and 51 healthcare workers (HCWs) enrolled in the study, cluster analysis identified four distinct patterns of evolution characterised by specific immune patterns and clinical factors. We observed that immune responses appeared to be less robust in cluster A, whose individuals were mostly PLWH who had never been infected with SARS-CoV-2. Cluster C, whose individuals showed a particularly drastic increase in markers of humoral immune response following the third dose of vaccine, was mainly composed of female participants who experienced SARS-CoV-2. Regarding the correlation study, although we observed a strong positive correlation between markers mirroring humoral immune response, markers of T-cell response following vaccination correlated only in a lesser extent with markers of humoral immunity. This suggests that neutralising antibody titers alone are not always a reliable reflection of the magnitude of the whole immune response. (4) Conclusions: Our findings show heterogeneity in immune responses among SARS-CoV-2 vaccinated PLWH. Specific subgroups could therefore benefit from distinct immunization strategies. Prior or breakthrough natural infection enhances the activity of vaccines and must be taken into account for informing global vaccine strategies among PLWH, even those with a viro-immunologically controlled infection.

Virus-Specific T-Cell Therapy for Viral Infections of the Central Nervous System: A Review.

Opportunistic viral infections of the central nervous system represent a significant cause of morbidity and mortality among an increasing number of immunocompromised patients. Since antiviral treatments are usually poorly effective, the prognosis generally relies on the ability to achieve timely immune reconstitution. Hence, strategies aimed at reinvigorating antiviral immune activity have recently emerged. Among these, virus-specific T-cells are increasingly perceived as a principled and valuable tool to treat opportunistic viral infections. Here we briefly discuss how to develop and select virus-specific T-cells, then review their main indications in central nervous system infections, including progressive multifocal leukoencephalopathy, CMV infection, and adenovirus infection. We also discuss their potential interest in the treatment of progressive multiple sclerosis, or EBV-associated central nervous system inflammatory disease. We finish with the key future milestones of this promising treatment strategy.

Human Immunodeficiency Virus Viral Load Monitoring and Rate of Virologic Suppression Among Patients Receiving Antiretroviral Therapy in Democratic Republic of the Congo, 2013-2020.

Background: Antiretroviral therapy (ART) expansion and viral load as a treatment monitoring approach have increased the demand for viral load testing. Many hurdles affect the coverage, quality, and use of viral load results. Estimates of viral load monitoring and viral suppression rates are needed to assess the performance of ART programs and improve human immunodeficiency virus (HIV) management outcomes. Methods: People with HIV (PWH) viral load monitoring data were routinely collected in 84 health facilities in Kinshasa, Democratic Republic of the Congo (DRC), between 2013 and 2020. The number of PWH under ART, the number of participants with at least 1 viral load test result, the rate of viral suppression (defined as ≤1000 HIV ribonucleic acid copies per mL), and the mean turnaround time from sample collection to release of viral load test results were collected together with clinical data. Results: A total of 14 057 PWH were included in the analysis. People with HIV were mainly enrolled after the "test and treat" implementation. The patients were followed for a median period of 27 months. The proportion of PWH with at least 1 available viral load largely increased in recent years. The delay from sample collection to release of viral load test results decreased overtime, from 35 days in 2018 to 16 days in 2020. Pregnancy and advanced HIV disease were associated with a lower chance of viral suppression. Conclusions: There has been considerable success in increasing viral load access for all PWH under therapy in DRC. Nevertheless, viral load testing should be intensified with a particular effort to be made in groups at higher risk of viral failure.

[An emerging cause of chronic fatigue and pain : post-COVID-19 condition or long COVID]. / Une cause émergente de fatigue et de douleurs chroniques : l'affection post-COVID-19 ou COVID long.

Some individuals who have been infected with SARS-CoV-2 can experience long-term effects from their infection, known as post-COVID conditions, post-acute sequelae of COVID-19 or long COVID. Different underlying mechanisms can lead to long COVID, none of which are mutually exclusive. Lingering symptoms can persist years after SARS-CoV-2 infection, including fatigue, muscle weakness, tachycardia, dyspnea and various neurological symptoms. The symptomatology is partly similar to that reported by people with chronic fatigue syndrome and other unwell studied long-lasting diseases that may occur after other infections. People who have experienced more severe COVID-19 illness are at higher risk of developing long COVID, although anyone who was infected can experience post-COVID conditions. Importantly, unvaccinated individuals are more likely to develop long COVID. Here we review the current knowledge and discuss key findings regarding the epidemiology and physiopathology of long COVID. We briefly review current diagnostic and treatment options that remain so far largely insufficient.

Certains individus infectés par le SARS-CoV-2 peuvent présenter des symptômes à long terme, évoluant parfois durant plusieurs années. Il est alors question d'affection post-COVID-19 ou COVID long. Les symptômes sont très polymorphes, fluctuants, et comprennent, notamment, une fatigue intense, des douleurs articulaires et musculaires, de la dyspnée, de la tachycardie, ainsi qu'une constellation de plaintes neurologiques. Cette symptomatologie est, en partie, similaire à celle du syndrome de fatigue chronique et est retrouvée également après d'autres types d'infections. Les mécanismes à l'origine du COVID long sont probablement multiples et encore mal connus. Si le COVID long peut toucher tout individu infecté par le SARS-CoV-2, certains groupes sont plus à risque, notamment les personnes non vaccinées ou les individus ayant présenté une infection sévère. Dans cet article, nous résumons les connaissances actuelles et mettons en lumière les découvertes clés quant à l'épidémiologie et aux mécanismes physiopathologiques du COVID long. Nous discutons aussi des critères diagnostiques et des options thérapeutiques qui sont, à ce jour, largement insuffisantes.

Kinetics and Persistence of the Cellular and Humoral Immune Responses to BNT162b2 mRNA Vaccine in SARS-CoV-2-Naive and -Experienced Subjects: Impact of Booster Dose and Breakthrough Infections.

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 cellular and humoral immune response in healthcare workers up to 12 months after the initial vaccination, with one additional boosting dose between 6 and 12 months. Methods: This prospective study enrolled 208 healthcare workers (HCWs) from the Liège University Hospital (CHU) of Liège in Belgium. Participants received two doses of BioNTech/Pfizer COVID-19 vaccine (BNT162b2) and a booster dose 6-12 months later. Fifty participants were SARS-CoV-2 experienced and 158 were naïve 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), 6 months (T4) and 12 months (T5) after the second dose. Between T4 and T5, participants also got the third boosting vaccine dose. A total of 1145 blood samples were collected. All samples were tested for the presence of anti-Spike antibodies, using the DiaSorin LIAISON SARS-CoV-2 Trimeric S IgG assay, and for anti-Nucleocapsid antibodies, using Elecsys anti-SARS-CoV-2 assay​​. Neutralizing antibodies against the SARS-CoV-2 Wuhan-like variant strain were quantified in all samples using a Vero E6 cell-based neutralization assay. Cell-mediated immune response was evaluated at T4 and T5 on 80 and 55 participants, respectively, by measuring the secretion of IFN-γ on peripheral blood lymphocytes using the QuantiFERON Human IFN-γ SARS-CoV-2, from Qiagen. 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 HCWs compared to naïve HCWs at all time points analyzed except the one after boosting dose. Cellular immune response was also higher in experienced HCWs six months following vaccination. Besides the impact of SARS-CoV-2 infection history on immune response to BNT162b2 mRNA vaccine, we observed a significant negative association between age and persistence of humoral response. The booster dose induced an increase in humoral and cellular immune responses, particularly in naive individuals. Breakthrough infections resulted in higher cellular and humoral responses after the booster dose. 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. The benefit of the booster dose was greater in naive individuals. 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.

Evaluation of Screening Program and Phylogenetic Analysis of SARS-CoV-2 Infections among Hospital Healthcare Workers in Liège, Belgium.

Healthcare workers (HCWs) are known to be at higher risk of developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections although whether these risks are equal across all occupational roles is uncertain. Identifying these risk factors and understand SARS-CoV-2 transmission pathways in healthcare settings are of high importance to achieve optimal protection measures. We aimed to investigate the implementation of a voluntary screening program for SARS-CoV-2 infections among hospital HCWs and to elucidate potential transmission pathways though phylogenetic analysis before the vaccination era. HCWs of the University Hospital of Liège, Belgium, were invited to participate in voluntary reverse transcriptase-polymerase chain reaction (RT-PCR) assays performed every week from April to December 2020. Phylogenetic analysis of SARS-CoV-2 genomes were performed for a subgroup of 45 HCWs. 5095 samples were collected from 703 HCWs. 212 test results were positive, 15 were indeterminate, and 4868 returned negative. 156 HCWs (22.2%) tested positive at least once during the study period. All SARS-CoV-2 test results returned negative for 547 HCWs (77.8%). Nurses (p < 0.05), paramedics (p < 0.05), and laboratory staff handling respiratory samples (p < 0.01) were at higher risk for being infected compared to the control non-patient facing group. Our phylogenetic analysis revealed that most positive samples corresponded to independent introduction events into the hospital. Our findings add to the growing evidence of differential risks of being infected among HCWs and support the need to implement appropriate protection measures based on each individual's risk profile to guarantee the protection of both HCWs and patients. Furthermore, our phylogenetic investigations highlight that most positive samples correspond to distinct introduction events into the hospital.

Killing Two Birds With One Stone: Effective Control of Both Non-Small Cell Lung Cancer and Progressive Multifocal Leukoencephalopathy With Atezolizumab, A Case Report.

Treating patients with cancer complicated by severe opportunistic infections is particularly challenging since classical cancer treatments, such as chemotherapy, often induce profound immune suppression and, as a result, may favor infection progression. Little is known about the potential place of immune checkpoint inhibitors in these complex situations. Here, we report a 66-year-old man who was concomitantly diagnosed with non-small cell lung cancer and progressive multifocal leukoencephalopathy. The patient was treated with anti-PD-L1 antibody atezolizumab, which allowed effective control of both lung cancer and progressive multifocal leukoencephalopathy, as demonstrated by the patient's remarkable neurologic clinical improvement, JC viral load reduction in his cerebrospinal fluid, regression of the brain lesions visualized through MRI, and the strict radiological stability of his cancer. In parallel, treatment with atezolizumab was associated with biological evidence of T-cell reinvigoration. Hence, our data suggest that immune checkpoint inhibitors may constitute a treatment option for patients with cancer complicated by severe opportunistic infections.

Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy: Identifying relevant outcome factors.

INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is an infectious brain disease caused by JC virus in immunocompromised individuals. Immune checkpoint inhibitors (ICIs) recently emerged as a therapeutic hope for these patients but identification of those likely to respond to the treatment is still an unmet need. METHOD: We performed a systematic PubMed search for reports of patients treated for PML using an ICI. Clinical, biological and radiological characteristics were contrasted between patients who responded to the treatment (RP) and those who did not (NRP). RESULTS: Thirty-five patients were included in the present study. Twenty-one of them reportedly benefited from the treatment. Age, blood CD4+ cells count, pretreatment viral load in the cerebrospinal fluid (CSF), PML lesions localization, treatment delay since first PML symptoms, type of ICI used and immune-related adverse events (irAEs) occurrence did not significantly differ between RP and NRP. By contrast, a history of therapeutic immune suppression and the use of an immunosuppressive therapy at treatment initiation were significantly associated with a poor response. Besides, reaching an undetectable viral load in the CSF and reduction of the lesion load on magnetic resonance imaging after ICI administration was associated with a good clinical response. CONCLUSION: Current data suggest that patients with PML under immunosuppressive therapy are less likely to respond to ICIs and raises the issue of the optimal management of irAEs during ICI treatment in this setting.

Impact of the COVID-19 pandemic situation on HIV care in Liège, Belgium.

BACKGROUND: 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: Objective: To study the impact of the COVID-19 pandemic on the holistic care of people living with HIV in Liège (Belgium). METHODS: 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: 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: 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.

Lung and liver sarcoidosis-like reaction induced by tocilizumab.

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 6 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.

Evolution of Drug Interactions With Antiretroviral Medication in People With HIV.

BACKGROUND: Polypharmacy and drug interactions are important issues for HIV-infected individuals. The number and nature of those interactions are continuously evolving with the use of new antiretroviral drugs and the aging of HIV-infected individuals. We aimed to analyze this evolution over time. METHODS: This retrospective cohort study was conducted in the University Hospital of Liège (Belgium). Treatments of HIV-infected outpatients attending Liège University Hospital were collected and analyzed in 2012 and 2016. The University of Liverpool HIV drug interactions database was used to determine drug interactions. RESULTS: We included 1038 patients in 2016, of whom 78% had 1 comedication. Polypharmacy was seen in 20% of the cohort. Four percent of the patients presented red flag interactions, and 38% had orange flag interactions. Nonantiretroviral (non-ARV) therapeutic classes involved in drug interactions were mostly cardiovascular and central nervous system drugs. They were followed by hormone drugs and dietary supplements for orange flag interactions. Two factors significantly contributed to both red and orange flag interactions: the number of non-ARV comedications and protease inhibitor-based ARV regimens. The proportion of patients with red or orange flag interactions remained stable from 2012 to 2016. CONCLUSIONS: This study highlights the persistence of an alarming number of contraindicated drug interactions and a high prevalence of potential drug interactions over time. Identification, prevention, and management of drug interactions remain a key priority in HIV care.