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This study aimed to investigate the SARS-CoV-2 infection prevalence among >18-year-old students in the Faculty of Public Health and Faculty of Sciences at the Lebanese University in Tripoli, Northern Lebanon, in June 2023 and to characterize the circulating Omicron subvariants. Out of 357 participants, only 2 (0.56%) tested positive by qPCR, corresponding to 0.61% (2/326) of asymptomatic students. One case tested positive with a qPCR targeting the Omicron BA.2 variant. These findings indicate a low incidence at that time and emphasize the interest of SARS-CoV-2 surveillance among students.

Since March 2020, the COVID-19 pandemic has swiftly propagated, triggering a competitive race among medical firms to forge vaccines that thwart the infection. Lebanon initiated its vaccination campaign on February 14, 2021. Despite numerous studies conducted to elucidate the characteristics of immune responses elicited by vaccination, the topic remains unclear. Here, we aimed to track the progression of anti-spike SARS-CoV-2 antibody titers at two-time points (T1: shortly after the second vaccination dose, T2: six months later) within a cohort of 201 adults who received Pfizer-BioNTech (BNT162b2), AstraZeneca, or Sputnik V vaccines in North Lebanon. Blood specimens were obtained from participants, and antibody titers against SARS-CoV-2 were quantified through the Elecsys-Anti-SARS-CoV-2 S assay (Roche Diagnostics, Switzerland). We used univariate analysis and multivariable logistic regression models to predict determinants influencing the decline in immune response and the occurrence of breakthrough infections among vaccinated patients. Among the 201 participants, 141 exhibited unchanging levels of antibody titers between the two sample collections, 55 displayed waning antibody titers, and only five participants demonstrated heightened antibody levels. Notably, age emerged as the sole variable significantly linked to the waning immune response. Moreover, the BNT162b2 vaccine exhibited significantly higher efficacy concerning the occurrence of breakthrough infections when compared with the AstraZeneca vaccine. Overall, our study reflected the immune status of a sample of vaccinated adults in North Lebanon. Further studies on a larger scale are needed at the national level to follow the immune response after vaccination, especially after the addition of the third vaccination dose.

Abstract There is a crucial need for non-sputum-based TB tests. Here, we evaluate the performance of RISK6, a human-blood transcriptomic signature, for TB screening, triage and treatment monitoring. RISK6 performance was also compared to that of two IGRAs: one based on RD1 antigens (QuantiFERON-TB Gold Plus, QFT-P, Qiagen) and one on recombinant M. tuberculosis HBHA expressed in Mycobacterium smegmatis (IGRA-rmsHBHA). In this multicenter prospective nested case–control study conducted in Bangladesh, Georgia, Lebanon and Madagascar, adult non-immunocompromised patients with bacteriologically confirmed active pulmonary TB (ATB), latent TB infection (LTBI) and healthy donors (HD) were enrolled. ATB patients were followed-up during and after treatment. Blood RISK6 scores were assessed using quantitative real-time PCR and evaluated by area under the receiver-operating characteristic curve (ROC AUC). RISK6 performance to discriminate ATB from HD reached an AUC of 0.94 (95% CI 0.89–0.99), with 90.9% sensitivity and 87.8% specificity, thus achieving the minimal WHO target product profile for a non-sputum-based TB screening test. Besides, RISK6 yielded an AUC of 0.93 (95% CI 0.85–1) with 90.9% sensitivity and 88.5% specificity for discriminating ATB from LTBI. Moreover, RISK6 showed higher performance (AUC 0.90, 95% CI 0.85–0.94) than IGRA-rmsHBHA (AUC 0.75, 95% CI 0.69–0.82) to differentiate TB infection stages. Finally, RISK6 signature scores significantly decreased after 2 months of TB treatment and continued to decrease gradually until the end of treatment reaching scores obtained in HD. We confirmed the performance of RISK6 signature as a triage TB test and its utility for treatment monitoring.

Background and Objectives: Due to their weakened immune response, hemodialysis (HD) patients with latent tuberculosis infection (LTBI) are at higher risk for active tuberculosis (TB) disease and are more subject to patient-to-patient transmission within dialysis units. Consequently, current guidelines advocate screening these patients for LTBI. To our knowledge, the epidemiology of LTBI in HD patients has never been examined before in Lebanon. In this context, this study aimed to determine LTBI prevalence among patients undergoing regular HD in Northern Lebanon and to identify potential factors associated with this infection. Notably, the study was conducted during the COVID-19 pandemic, which is likely to have catastrophic effects on TB and increase the risk of mortality and hospitalization in HD patients. Materials and Methods: A multicenter cross-sectional study was carried out in three hospital dialysis units in Tripoli, North Lebanon. Blood samples and sociodemographic and clinical data were collected from 93 HD patients. To screen for LTBI, all patient samples underwent the fourth-generation QuantiFERON-TB Gold Plus assay (QFT-Plus). Multivariable logistic regression analysis was used to identify the predictors of LTBI status in HD patients. Results: Overall, 51 men and 42 women were enrolled. The mean age of the study population was 58.3 ± 12.4 years. Nine HD patients had indeterminate QFT-Plus results and were therefore excluded from subsequent statistical analysis. Among the remaining 84 participants with valid results, QFT-Plus was positive in 16 patients, showing a positivity prevalence of 19% (95% interval for p: 11.3%, 29.1%). Multivariable logistic regression analysis showed that LTBI was significantly associated with age [OR = 1.06; 95% CI = 1.01 to 1.13; p = 0.03] and a low-income level [OR = 9.29; 95% CI = 1.62 to 178; p = 0.04]. Conclusion: LTBI was found to be prevalent in one in five HD patients examined in our study. Therefore, effective TB control measures need to be implemented in this vulnerable population, with special attention to elderly patients with low socioeconomic status.

Objectives: Tuberculosis (TB) is the leading infectious cause of death in the world. Cheaper and more accessible TB treatment monitoring methods are needed. Here, we evaluated white blood cell (WBC) absolute counts, lymphocyte, and monocyte proportions during TB treatment, and characterized their association with treatment failure. Methods: This multicentered prospective cohort study was based in Bangladesh, Georgia, Lebanon, Madagascar, and Paraguay. Adult, non-immunocompromised patients with culture-confirmed pulmonary TB were included and followed up after two months of treatment and at the end of therapy. Blood counts were compared to treatment outcome using descriptive statistics, logistic regression, and Receiver Operating Characteristic (ROC) analyses. Results: Between December 2017 and August 2020, 198 participants were enrolled, and 152 completed treatment, including 28 (18.5%) drug-resistant patients. The rate of cure at the end of treatment was 90.8% (138/152). WBC absolute counts decreased, and lymphocyte proportions increased throughout treatment. In multivariate analyses, baseline high WBC counts and low lymphocyte proportions were associated with positive sputum culture results at the end of treatment (WBC > 11,450 cells/mm3: p = 0.048; lymphocytes 11,450 cells/mm3 and lymphocytes

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterised by the accumulation into granulomas of apoptosis-resistant pathological dendritic cells (LCH-DCs). LCH outcome ranges from self-resolving to fatal. Having previously shown that, (i) monocyte-derived DCs (Mo-DCs) from LCH patients differentiate into abnormal and pro-inflammatory IL-17A-producing DCs, and (ii) recombinant IL-17A induces survival and chemoresistance of healthy Mo-DCs, we investigated the link between IL-17A and resistance to apoptosis of LCH-DCs. In LCH granulomas, we uncovered the strong expression of BCL2A1 (alias BFL1), an anti-apoptotic BCL2 family member. In vitro, intracellular IL-17A expression was correlated with BCL2A1 expression and survival of Mo-DCs from LCH patients. Based on the chemotherapeutic drugs routinely used as first or second line LCH therapy, we treated these cells with vinblastine, or cytarabine and cladribine. Our preclinical results indicate that high doses of these drugs decreased the expression of Mcl-1, the main anti-apoptotic BCL2 family member for myeloid cells, and killed Mo-DCs from LCH patients ex vivo, without affecting BCL2A1 expression. Conversely, neutralizing anti-IL-17A antibodies decreased BCL2A1 expression, the downregulation of which lowered the survival rate of Mo-DCs from LCH patients. Interestingly, the in vitro combination of low-dose vinblastine with neutralizing anti-IL-17A antibodies killed Mo-DCs from LCH patients. In conclusion, we show that BCL2A1 expression induced by IL-17A links the inflammatory environment to the unusual pro-survival gene activation in LCH-DCs. Finally, these preclinical data support that targeting both Mcl-1 and BCL2A1 with low-dose vinblastine and anti-IL-17A biotherapy may represent a synergistic combination for managing recurrent or severe forms of LCH.

In a 12-month nationwide study on the prevalence of drug-resistant tuberculosis (TB) in Lebanon, we identified 3 multidrug-resistant cases and 3 extensively drug-resistant TB cases in refugees, migrants, and 1 Lebanon resident. Enhanced diagnostics, particularly in major destinations for refugees, asylum seekers, and migrant workers, can inform treatment decisions and may help prevent the spread of drug-resistant TB.

In the present study, we provide a retrospective genomic surveillance of the SARS-CoV-2 pandemic in Lebanon; we newly sequence the viral genomes of 200 nasopharyngeal samples collected between July 2020 and February 2021 from patients in different regions of Lebanon and from travelers crossing the Lebanese–Syrian border, and we also analyze the Lebanese genomic dataset available at GISAID. Our results show that SARS-CoV-2 infections in Lebanon during this period were shaped by the turnovers of four dominant SARS-CoV-2 lineages, with B.1.398 being the first to thoroughly dominate. Lebanon acted as a dispersal center of B.1.398 to other countries, with intercontinental transmissions being more common than within-continent. Within the country, the district of Tripoli, which was the source of 43% of the total B.1.398 sequences in our study, was identified as being an important source of dispersal in the country. In conclusion, our findings exemplify the butterfly effect, by which a lineage that emerges in a small area can be spread around the world, and highlight the potential role of developing countries in the emergence of new variants.

BackgroundTuberculosis (TB) is a leading infectious cause of death. To improve treatment efficacy, quicker monitoring methods are needed. The objective of this study was to monitor the response to a heparin-binding hemagglutinin (HBHA) interferon-γ (IFN-γ) release assay (IGRA) and QuantiFERON-TB Gold Plus (QFT-P) and to analyze plasma IFN-γ levels according to sputum culture conversion and immune cell counts during treatment.MethodsThis multicentered cohort study was based in Bangladesh, Georgia, Lebanon, Madagascar, and Paraguay. Adult, non-immunocompromised patients with culture-confirmed pulmonary TB were included. Patients were followed up at baseline (T0), after two months of treatment (T1), and at the end of therapy (T2). Clinical data and blood samples were collected at each timepoint. Whole blood samples were stimulated with QFT-P antigens or recombinant methylated Mycobacterium tuberculosis HBHA (produced in Mycobacterium smegmatis; rmsHBHA). Plasma IFN-γ levels were then assessed by ELISA.FindingsBetween December 2017 and September 2020, 132 participants completed treatment, including 28 (21.2%) drug-resistant patients. rmsHBHA IFN-γ increased significantly throughout treatment (0.086 IU/ml at T0 vs. 1.03 IU/ml at T2, p < 0.001) while QFT-P IFN-γ remained constant (TB1: 0.53 IU/ml at T0 vs. 0.63 IU/ml at T2, p = 0.13). Patients with low lymphocyte percentages (79%) at baseline had significantly lower IFN-γ responses to QFT-P and rmsHBHA at T0 and T1. In a small group of slow converters (patients with positive cultures at T1; n = 16), we observed a consistent clinical pattern at baseline (high neutrophil percentages, low lymphocyte percentages and BMI, low TB1, TB2, and MIT IFN-γ responses) and low rmsHBHA IFN-γ at T1 and T2. However, the accuracy of the QFT-P and rmsHBHA IGRAs compared to culture throughout treatment was low (40 and 65% respectively). Combining both tests improved their sensitivity and accuracy (70–80%) but not their specificity (

Plasma IL-17A detection in Langerhans Cell Histiocytosis (LCH) is currently a source of debate. Indeed, 500-P07G (PeproTech) and 41802 (R&D Systems) anti-IL-17A antibodies have been suspected to recognize nonspecific proteins. To resolve this discrepancy, we set up two new ELISAs by using 41802 or neutralizing eBio64CAP17 (eBioscience) capture monoclonal antibodies that we compared to the commercial PeproTech ELISA kit. The three ELISAs, called E_500-P07G, E_41802 and E_eBio64CAP17, differ in their anti-IL-17A capture antibodies: either polyclonal, monoclonal or neutralizing monoclonal antibodies, respectively. Here, we show that these ELISAs had a similar capacity to specifically detect recombinant or native human IL-17A. However, a significantly lower plasma IL-17A detection was obtained with E_41802 compared to the two other ELISAs. Both E_500-P07G and E_eBio64CAP17 showed similar results. Consequently, we propose that the use of E_500-P07G and E_eBio64CAP17 may ensure more accurate and reliable results in the context of LCH studies. The highest plasma IL-17A levels in LCH patients compared to controls detected by both E_500-P07G and E_eBio64CAP17 ELISAs led us to propose these latter as reference techniques to investigate IL-17A as a potential new biomarker in LCH. • The customization of a new E_eBio64CAP17 ELISA is suitable to detect human IL-17A. • E_eBio64CAP17 ELISA protocol differs only in the anti-IL-17A capture antibody compared to the commercial E_500-P07G PeproTech kit. • Data generated using the E_eBio64CAP17 ELISA are consistent with the PeproTech kit.

Hepatitis E virus (HEV) is an important global public health concern. Several studies reported a higher HEV prevalence in patients undergoing regular hemodialysis (HD). In Lebanon, the epidemiology of HEV among HD patients has never been investigated previously. In this study, we examine the seroprevalence of HEV infection among 171 HD patients recruited from three hospital dialysis units in Tripoli, North Lebanon. Prevalence of anti-HEV IgG antibodies was evaluated in participant's sera using a commercial enzyme-linked immunosorbent assay (ELISA). The association of socio-demographic and clinical parameters with HEV infection in patients was also evaluated. Overall, 96 women and 75 men were enrolled in this study. Anti-HEV IgG antibodies were found positive in 37/171 HD patients showing a positivity rate of 21.63%. Among all examined variables, only the age of patients was significantly associated with seropositivity (P = 0.001). This first epidemiological study reveals a high seroprevalence of HEV infection among Lebanese HD patients. However, further evaluations that enroll larger samples and include control groups are required to identify exact causative factors of the important seropositivity rate in this population.

Background and Objectives: Several LAB species were evaluated and characterized for potential probiotic use. Besides the antimicrobial activity, probiotics showed recently a capacity to prevent and to alleviate inflammatory and chronic diseases. Immunomodulation effect is one of the modes of actions of such probiotics, called immunobiotics, which can be used in several chronic diseases such as Inflammatory Bowel Diseases (IBD). The aim of this study was to isolate, identify and characterize lactobacilli strains from healthy baby’s feces in order to select some strains with potential immunobiotic application especially strains which can stimulate anti-inflammatory responses. Materials and Methods: Forty-two LAB strains were isolated and identified by the MALDI-TOF / MS technique. In addition, strains were subjected to several assessments such as antimicrobial activity, the capacity to form biofilm in polystyrene microplate and immunomodulation activity in a PBMC model. Results: Results showed that the majority of strains (90.4%) were identified as Lactobacillus. However, among these, only 39.4% of lactobacilli strains were not identified at the species level. All isolated lactobacilli strains showed an anti-inflammatory effect. Moreover, 7 strains were considered as good probiotic candidates based on their characteristics such as their antibacterial activities, formation of the strongest biofilm and their ability to stimulate an anti-inflammatory response in PBMCs model. Conclusion: Two strains (Lactobacillus spp S14 and Lactobacillus spp S49) which showed the best immunobiotic characteristics, could be selected and evaluated more deeply in vivo model as well as in human clinical study to ensure their effectiveness in inflammatory diseases such as IBD.

Secondary bacterial infections contribute to the excess morbidity and mortality of influenza A virus (IAV) infection. Disruption of lung integrity and impaired antibacterial immunity during IAV infection participate in colonization and dissemination of the bacteria out of the lungs. One key feature of IAV infection is the profound alteration of lung myeloid cells, characterized by the recruitment of deleterious inflammatory monocytes. We herein report that IAV infection causes a transient decrease of lung conventional dendritic cells (cDCs) (both cDC1 and cDC2) peaking at day 7 post-infection. While triggering emergency monopoiesis, IAV transiently altered the differentiation of cDCs in the bone marrow, the cDC1-biaised pre-DCs being particularly affected. The impaired cDC differentiation during IAV infection was independent of type I interferons (IFNs), IFN-γ, TNFα and IL-6 and was not due to an intrinsic dysfunction of cDC precursors. The alteration of cDC differentiation was associated with a drop of local and systemic production of Fms-like tyrosine kinase 3 ligand (Flt3-L), a critical cDC differentiation factor. Overexpression of Flt3-L during IAV infection boosted the cDC progenitors' production in the BM, replenished cDCs in the lungs, decreased inflammatory monocytes' infiltration and lowered lung damages. This was associated with partial protection against secondary pneumococcal infection, as reflected by reduced bacterial dissemination and prolonged survival. These findings highlight the impact of distal viral infection on cDC genesis in the BM and suggest that Flt3-L may have potential applications in the control of secondary infections.

Rheumatoid arthritis (RA) and Langerhans cell histiocytosis (LCH) are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC), and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.