Risk Factors for SARS-CoV-2 Among a Cohort of Healthcare Workers in Lebanon.

BACKGROUND: Healthcare workers (HCWs) faced substantial risk of infection during the COVID-19 outbreak. This study aims to determine the prevalence of anti-SARS-CoV-2 antibodies in a cross-sectional sample of HCWs as well as risk factors associated with exposure to SARS-CoV-2. METHODS: The study was conducted between March and May 2021 at the American University of Beirut Medical Center (AUBMC), a tertiary hospital located in Lebanon. Socio-demographic and clinical data, as well as data on exposure, PCR results, PPE adherence, and vaccination status, were collected using an online questionnaire. Sera were also collected to determine seropositivity using commercially available enzyme-linked immunoassay (ELISA) targeting the spike (S) and the nucleocapsid proteins (NCP) of SARS-CoV-2. FINDINGS: Among 92 recruited HCWs, 72.3% received PPE training, more than 70% were adherent to using appropriate PPEs, and around 80% were vaccinated. Nurses in this study population were at higher risk of exposure compared to medical doctors, technicians, and other HCWs. Among the HCWs who performed a PCR test, 28.6% were infected with SARs-CoV-2 with workplace exposure not associated with COVID-19 infection. All vaccinated HCWs were seropositive for anti-S IgG with high titer (≥384 BAU/mL), with a significantly higher median anti-S IgG titer compared to unvaccinated HCWs with previous infection (384 vs. 140.1 BAU/mL; p = .0043). CONCLUSIONS: Our study highlights the importance of implementing strict infection control policies among HCWs and deploying an effective COVID-19 vaccination strategy. More studies are needed in Lebanon to assess risk factors of SARS-CoV-2 exposure in the workplace.

An obesogenic diet increases atherosclerosis through promoting microbiota dysbiosis-induced gut lymphocyte trafficking into the periphery.

Although high-fat diet (HFD)-induced gut microbiota dysbiosis is known to affect atherosclerosis, the underlying mechanisms remain to be fully explored. Here, we show that the progression of atherosclerosis depends on a gut microbiota shaped by an HFD but not a high-cholesterol (HC) diet and, more particularly, on low fiber (LF) intake. Mechanistically, gut lymphoid cells impacted by HFD- or LF-induced microbiota dysbiosis highly proliferate in mesenteric lymph nodes (MLNs) and migrate from MLNs to the periphery, which fuels T cell accumulation within atherosclerotic plaques. This is associated with the induction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) within plaques and the presence of enterotropic lymphocytes expressing ß7 integrin. MLN resection or lymphocyte deficiency abrogates the pro-atherogenic effects of a microbiota shaped by LF. Our study shows a pathological link between a diet-shaped microbiota, gut immune cells, and atherosclerosis, suggesting that a diet-modulated microbiome might be a suitable therapeutic target to prevent atherosclerosis.

Clinical Characteristics and Serum Cytokines Profiling in Hospitalized COVID-19 Patients in Lebanon.

Since its emergence, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a public health threat worldwide. While the majority of patients recover in 3-4 weeks, complications in severely ill patients, including acute respiratory distress syndrome, cardiac injury, thrombosis, and sepsis, can lead to death. Several biomarkers, in addition to cytokine release syndrome (CRS), have been associated with severe and fatal outcomes in coronavirus disease 2019 (COVID-19) patients. The aim of this study is to assess clinical characteristics and cytokines profiles in hospitalized COVID-19 patients in Lebanon. A total of 51 hospitalized COVID-19 patients were recruited between February 2021 and May 2022. Clinical data and sera were collected at two time points: at hospital presentation (T0) and last collected results during hospitalization (T1). Our results showed that 49% of participants were >60 years with males accounting for the majority (72.5%). Hypertension, followed by diabetes and dyslipidemia, were the most frequent comorbid conditions among study participants accounting for 56.9% and 31.4%, respectively. Chronic obstructive pulmonary disease (COPD) was the only significantly different comorbid condition between intensive care unit (ICU) and non-ICU patients. Our results also showed that the median level of D-dimer was significantly elevated among patients in ICU and those who died compared to non-ICU patients and those who survived. Moreover, C-reactive protein (CRP) levels were significantly higher at T0 compared to T1 in ICU and non-ICU patients. The median level of IL-12p70 was significantly higher in patients >60 years compared to those ≤60 years (p = 0.0209). Our data are in agreement with previous reports suggesting the importance of IL-6, CRP, and IL-12p70 in the assessment of risk of severe disease and mortality.

COVID-19 Infections and Predictors of Sickness Related Absences Among Healthcare Workers: The Experience of a Tertiary Care Center With the COVID-19 Pandemic.

BACKGROUND: Little has been published on predictors of prolonged sick leaves during the COVID-19 pandemic. This study aims to determine the rate of COVID-19 infections among healthcare workers (HCWs) and to identify the predictors of longer sick leave days. METHODS: We identified predictors of longer sick leave using linear regression analysis in a cross-sectional study design. RESULTS: Thirty-three percent of the total workforce contracted COVID-19. On average, HCWs took 12.5 sick leave days after COVID-19 infection. The regression analysis revealed that older employees, nurses, and those who caught COVID-19 earlier in the pandemic were more likely to take longer sick leave. CONCLUSIONS: Age, job position, and month of infection predicted sick leave duration among HCWs in our sample. Results imply that transmission was most likely community-based. Public health interventions should consider these factors when planning for future pandemics.

Response to COVID-19 in Lebanon: update, challenges and lessons learned.

The COVID-19 pandemic remains a public health problem threatening national and global health security. The socio-economic impact of COVID-19 was more severe on developing countries including Lebanon, especially due to the fragile healthcare system, weak surveillance infrastructure and lack of comprehensive emergency preparedness and response plans. Lebanon has been struggling with plethora of challenges at the social, economic, financial, political and healthcare levels prior to the COVID-19 pandemic. The COVID-19 pandemic in Lebanon revealed gaps and challenges across the spectrum of preparedness and response to emergencies. Despite these challenges, the Lebanese response was successful in delaying the steep surge of COVID-19 cases and hospitalisations through imposing strict public health and social measures. The deployment of the national vaccination plan in Lebanon in February 2021 coincided with the reduction in the number of cases and hospitalisation rates. The aim of this manuscript is to advance the epidemiologic evolution of COVID-19 in Lebanon pre- and post-vaccination, the challenges affecting the response and recovery, and the lessons learned.

Genomic surveillance of SARS-CoV-2 in COVID-19 vaccinated healthcare workers in Lebanon.

BACKGROUND: The emergence of SARS-CoV-2 variants including the Delta and Omicron along with waning of vaccine-induced immunity over time contributed to increased rates of breakthrough infection specifically among healthcare workers (HCWs). SARS-CoV-2 genomic surveillance is an important tool for timely detection and characterization of circulating variants as well as monitoring the emergence of new strains. Our study is the first national SARS-CoV-2 genomic surveillance among HCWs in Lebanon. METHODS: We collected 250 nasopharyngeal swabs from HCWs across Lebanon between December 2021 and January 2022. Data on the date of positive PCR, vaccination status, specific occupation, and hospitalization status of participants were collected. Extracted viral RNA from nasopharyngeal swabs was converted to cDNA, library prepped using the coronaHIT method, followed by whole genome sequencing on the Illumina NextSeq 500 platform. RESULTS: A total of 133 (57.1%) samples belonging to the Omicron (BA.1.1) sub-lineage were identified, as well as 44 (18.9%) samples belonging to the BA.1 sub-lineage, 28 (12%) belonging to the BA.2 sub-lineage, and only 15 (6.6%) samples belonging to the Delta variant sub-lineage B.1.617.2. These results show that Lebanon followed the global trend in terms of circulating SARS-CoV-2 variants with Delta rapidly replaced by the Omicron variant. CONCLUSION: This study underscores the importance of continuous genomic surveillance programs in Lebanon for the timely detection and characterization of circulating variants. The latter is critical to guide public health policy making and to timely implement public health interventions.

Trends & predictors of non-AIDS comorbidities among people living with HIV and receiving antiretroviral therapy in Lebanon.

ABSTRACT: Combined antiretroviral therapy (cART) increased the life expectancy of people living with Human Immunodeficiency Virus (HIV) (PLHIV) and remarkably reduced the morbidity and mortality associated with HIV infection. Consequently, PLHIV are experiencing non-acquired immunodeficiency syndrome (AIDS) associated comorbid conditions including diabetes, hyperlipidemia, hypertension, and cardiovascular disease. The aim of this study is to determine the frequency of non-AIDS associated comorbid conditions among a cohort of PLHIV on cART in Lebanon.Data were collected between November 2018 and December 2019 from 105 voluntary participants. A standardized questionnaire was used to collect demographic and behavioral data including lifestyle, smoking, physical activity, substance use and abuse in addition to co-infections and family history of non-communicable diseases. Moreover, data on occurrence and treatment of cardiovascular disease, hypertension, diabetes, lipid and metabolic disorders as well as mental health were collected. Blood samples were used to assess the levels of fasting blood sugar (FBS), glycosylated hemoglobin (HbA1C), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein, total cholesterol, and serum creatinine.Hypertension (29.5%) and hyperlipidemia (29.5%) followed by diabetes (23.7%) and cardiovascular disease (9.7%) were mainly reported among study participants. Higher rate of comorbid conditions was observed among participants >40 years of age than those ≤40 years with both hypertension and hyperlipidemia most commonly reported. Older age (odds ratio [OR] 7.6; 95% CI: 1.83-31.98; P = .005) is associated with higher odds of having hyperlipidemia. Moreover, participants on cART for ≥10 years are 5 times more likely to have hyperlipidemia (OR 5; 95% CI: 1.08-22.73; P = .039). Our results also showed that study participants did not experience anxiety, depression or somatic symptoms and that there was no association between these mental disorders and older age or comorbidities.Our results provide important information on HIV trends and associated comorbidities in Lebanon and can be used to improve the management of non-communicable diseases among PLHIV.

Expression of Killer Immunoglobulin Receptor Genes among HIV-Infected Individuals with Non-AIDS Comorbidities.

Combined antiretroviral therapy (cART) increased the life expectancy of people living with HIV (PLHIV) and remarkably reduced the morbidity and mortality associated with HIV infection. However, non-AIDS associated comorbidities including diabetes, hypertension, hyperlipidemia, and cardiovascular diseases (CVD) are increasingly reported among PLHIV receiving cART. Killer cell immunoglobulin receptors (KIRs) expressed on the surface of natural killer (NK) cells have been previously implicated in controlling HIV disease progression. The aim of this study is to investigate the role of KIRs in developing non-AIDS associated comorbidities among PLHIV. Demographic and behavioral data were collected from voluntary participants using a standardized questionnaire. Whole blood samples were collected for KIR genotyping. Hypertension (29.5%) and hyperlipidemia (29.5%) followed by diabetes (23.7%) and CVD (9.7%) were mainly reported among our study participants with higher rate of comorbid conditions observed among participants > 40 years old. The observed KIR frequency (OF) was ≥90% for inhibitory KIR2DL1 and KIR3DL1, activating KIR2DS4 and the pseudogene KIR2DP1 among study participants. We detected significant differences in the expression of KIR3DS4 and KIR3DL1 (p = 0.038) between diabetic and nondiabetic and in the expression of KIR2DL3 between hypertensive and normotensive HIV-infected individuals (p = 0.047). Moreover, KIR2DL1 and KIR2DP1 were associated with significantly reduced odds of having CVD (OR 0.08; 95% CI: 0.01-0.69; p = 0.022). Our study suggests the potential role of KIR in predisposition to non-AIDS comorbidities among PLHIV and underscores the need for more studies to further elucidate the role of KIRs in this population.

Tryptophan: From Diet to Cardiovascular Diseases.

Cardiovascular disease (CVD) is one of the major causes of mortality worldwide. Inflammation is the underlying common mechanism involved in CVD. It has been recently related to amino acid metabolism, which acts as a critical regulator of innate and adaptive immune responses. Among different metabolites that have emerged as important regulators of immune and inflammatory responses, tryptophan (Trp) metabolites have been shown to play a pivotal role in CVD. Here, we provide an overview of the fundamental aspects of Trp metabolism and the interplay between the dysregulation of the main actors involved in Trp metabolism such as indoleamine 2, 3-dioxygenase 1 (IDO) and CVD, including atherosclerosis and myocardial infarction. IDO has a prominent and complex role. Its activity, impacting on several biological pathways, complicates our understanding of its function, particularly in CVD, where it is still under debate. The discrepancy of the observed IDO effects could be potentially explained by its specific cell and tissue contribution, encouraging further investigations regarding the role of this enzyme. Thus, improving our understanding of the function of Trp as well as its derived metabolites will help to move one step closer towards tailored therapies aiming to treat CVD.

Endothelial Cell Indoleamine 2, 3-Dioxygenase 1 Alters Cardiac Function After Myocardial Infarction Through Kynurenine.

BACKGROUND: Ischemic cardiovascular diseases, particularly acute myocardial infarction (MI), is one of the leading causes of mortality worldwide. Indoleamine 2, 3-dioxygenase 1 (IDO) catalyzes 1 rate-limiting step of L-tryptophan metabolism, and emerges as an important regulator of many pathological conditions. We hypothesized that IDO could play a key role to locally regulate cardiac homeostasis after MI. METHODS: Cardiac repair was analyzed in mice harboring specific endothelial or smooth muscle cells or cardiomyocyte or myeloid cell deficiency of IDO and challenged with acute myocardial infarction. RESULTS: We show that kynurenine generation through IDO is markedly induced after MI in mice. Total genetic deletion or pharmacological inhibition of IDO limits cardiac injury and cardiac dysfunction after MI. Distinct loss of function of IDO in smooth muscle cells, inflammatory cells, or cardiomyocytes does not affect cardiac function and remodeling in infarcted mice. In sharp contrast, mice harboring endothelial cell-specific deletion of IDO show an improvement of cardiac function as well as cardiomyocyte contractility and reduction in adverse ventricular remodeling. In vivo kynurenine supplementation in IDO-deficient mice abrogates the protective effects of IDO deletion. Kynurenine precipitates cardiomyocyte apoptosis through reactive oxygen species production in an aryl hydrocarbon receptor-dependent mechanism. CONCLUSIONS: These data suggest that IDO could constitute a new therapeutic target during acute MI.

Review of seasonal influenza vaccination in the Eastern Mediterranean Region: Policies, use and barriers.

Vaccination is the main control measure for influenza and its severe complications. To better understand the influenza vaccination situation in the Eastern Mediterranean Region, we conducted an extensive review of literature published between 2006 and 2016 in the region on influenza vaccine policies, use, recommendations and coverage. Forty-eight articles met the inclusion criteria. These originated from 11 of the 22 countries of the region, with most being from Saudi Arabia and Iran. The review revealed knowledge gaps and misconceptions about influenza and its vaccines even among healthcare workers. Most of the papers reviewed reported low coverage in the target populations. Limited literature on the number of countries with concrete national influenza vaccination policies was available, which may not accurately represent the situation in the Region. In conclusion, lack of awareness and knowledge are the main barriers to influenza vaccination, which remains very low in the Eastern Mediterranean Region. Countries of the region need to promote and invest in research on influenza vaccination, which is critical to inform evidence-based programmes and policies to improve vaccination rates and control influenza.

The Role of Natural Killer Cells and Regulatory T Cells While Aging with Human Immunodeficiency Virus.

Combined antiretroviral therapy (cART) has increased the quality of life of people living with HIV (PLHIV). Consequently, the number of PLHIV >50 years is increasing worldwide. Patients on cART are known to remain in a proinflammatory state. The latter is linked to the development of non-AIDS-related chronic conditions. Although the number of aging PLHIV is increasing, the effect of HIV infection on the process of aging is not fully understood. Understanding the complexity of aging with HIV by investigating the effect of the latter on different components of the innate and adaptive immune systems is important to reduce the impact of these comorbid conditions and improve the quality of life of PLHIV. The role of killer immunoglobulin receptors (KIRs), expressed on the surface of natural killer (NK) cells, and their human leukocyte antigen (HLA) ligands in the clearance, susceptibility to or disease progression following HIV infection is well established. However, data on the effect of KIR-HLA interaction in aging HIV-infected population and the development of non-AIDS-related comorbid conditions are lacking. Moreover, conflicting data exist on the role of regulatory T cells (Tregs) during HIV infection. The purpose of this review is to advance the current knowledge on the role of NK cells and Tregs while aging with HIV infection.

Seasonal influenza vaccination policies in the Eastern Mediterranean Region: Current status and the way forward.

BACKGROUND: The World Health Organization recommends annual influenza vaccination, especially in high-risk groups. Little is known about the adoption and implementation of influenza vaccination policies in the Eastern Mediterranean Region. METHODS: A survey was distributed to country representatives at the ministries of health of the 22 countries of the Region between December 2016 and February 2017 to capture data on influenza immunization policies, recommendations, and practices in place. RESULTS: Of the 20 countries that responded to the survey, 14 reported having influenza immunization policies during the 2015/2016 influenza season. All countries with an influenza immunization policy recommended vaccination for people with chronic medical conditions, healthcare workers and pilgrims. Two of the 20 countries did not target pregnant women. Eight countries used the northern hemisphere formulation, one used the southern hemisphere formulation and nine used both. Vaccination coverage was not monitored by all countries and for all target groups. Where reported, coverage of a number of target groups (healthcare workers, children) was generally low. Data on the burden of influenza and vaccine protection are scarce in the Region. CONCLUSIONS: Despite widespread policy recommendations on influenza vaccination, attaining high coverage rates remains a challenge in the Eastern Mediterranean Region. Tackling disparities in influenza vaccine accessibility and strengthening surveillance systems may increase influenza vaccine introduction and use.

Review of seasonal influenza vaccination in the Eastern Mediterranean Region: Policies, use and barriers.

Vaccination is the main control measure for influenza and its severe complications. To better understand the influenza vaccination situation in the Eastern Mediterranean Region, we conducted an extensive review of literature published between 2006 and 2016 in the region on influenza vaccine policies, use, recommendations and coverage. Forty-eight articles met the inclusion criteria. These originated from 11 of the 22 countries of the region, with most being from Saudi Arabia and Iran. The review revealed knowledge gaps and misconceptions about influenza and its vaccines even among healthcare workers. Most of the papers reviewed reported low coverage in the target populations. Limited literature on the number of countries with concrete national influenza vaccination policies was available, which may not accurately represent the situation in the Region. In conclusion, lack of awareness and knowledge are the main barriers to influenza vaccination, which remains very low in the Eastern Mediterranean Region. Countries of the region need to promote and invest in research on influenza vaccination, which is critical to inform evidence-based programmes and policies to improve vaccination rates and control influenza.

Predominant Role of Nuclear Versus Membrane Estrogen Receptor α in Arterial Protection: Implications for Estrogen Receptor α Modulation in Cardiovascular Prevention/Safety.

BACKGROUND: Although estrogen receptor α (ERα) acts primarily as a transcription factor, it can also elicit membrane-initiated steroid signaling. Pharmacological tools and transgenic mouse models previously highlighted the key role of ERα membrane-initiated steroid signaling in 2 actions of estrogens in the endothelium: increase in NO production and acceleration of reendothelialization. METHODS AND RESULTS: Using mice with ERα mutated at cysteine 451 (ERaC451A), recognized as the key palmitoylation site required for ERα plasma membrane location, and mice with disruption of nuclear actions because of inactivation of activation function 2 (ERaAF20 = ERaAF2°), we sought to fully characterize the respective roles of nuclear versus membrane-initiated steroid signaling in the arterial protection conferred by ERα. ERaC451A mice were fully responsive to estrogens to prevent atheroma and angiotensin II-induced hypertension as well as to allow flow-mediated arteriolar remodeling. By contrast, ERαAF20 mice were unresponsive to estrogens for these beneficial vascular effects. Accordingly, selective activation of nuclear ERα with estetrol was able to prevent hypertension and to restore flow-mediated arteriolar remodeling. CONCLUSIONS: Altogether, these results reveal an unexpected prominent role of nuclear ERα in the vasculoprotective action of estrogens with major implications in medicine, particularly for selective nuclear ERα agonist, such as estetrol, which is currently under development as a new oral contraceptive and for hormone replacement therapy in menopausal women.

The epidemiology of Norovirus in the Middle East and North Africa (MENA) region: a systematic review.

Norovirus (NoV) is considered the second leading cause of viral acute gastroenteritis (AGE). To our knowledge, there are no systematic reviews assessing the role of NoV in AGE in the Middle East and North Africa (MENA) region. Consequently, we conducted an extensive systematic literature review on articles studying NoV in the 24 countries of the MENA region during the past 15 years (2000-2015). The methods and reporting were set according to the 2015 PRISMA-P and based on the elements from the international prospective register of systematic reviews (PROSPERO). We retrieved 38 studies meeting our predefined inclusion criteria and were used to extract full data. Studies reporting on NoV were conducted in 15 out of the 24 countries of the region. The reported NoV infection rates in MENA countries ranged between 0.82% and 36.84%. The majority of studies were clinical observational studies assessing NoV rates mainly among children. Participants were recruited from in- and outpatient clinics. NoV infection was reported all year round with with peaks observed mainly during cold months. GII.4 was the predominant genotype detected in stool of participants as reported by 16 out of 25 studies (64%). Overall, there is an increasing recognition of NoV as an important causative agent of AGE across all age groups in the MENA region. Further studies are needed to assess the national and the regional burden of NoV among different age groups, its molecular diversity and seasonal variability.

Update on the epidemiology of rotavirus in the Middle East and North Africa.

Rotavirus (RV) is the leading cause of severe acute gastroenteritis (AGE) worldwide. Consequently, we conducted a systematic literature review on articles studying RV in the 25 countries of the MENA region during the past 15years (2000-2015). The methods and reporting were set according to the 2015 preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) and based on the elements from the international prospective register of systematic reviews (PROSPERO). Our literature search identified 169 studies meeting our predefined inclusion criteria. Studies reporting on RV were conducted in 19 out of the 24 countries of the MENA region. The largest number of studies was reported in Turkey (n=32), Iran (n=31), Saudi Arabia (n=19) and Egypt (n=17). The majority of studies reporting on RV gastroenteritis rates were clinical observational studies. In 115 studies out of 169, RV was reported among in-patients whereas 35 studies reported RV among outpatients. The predominantly reported RV genotype in the region was G1[P8] followed by G2[P4] and G9[P8]. The majority of studies (n=108) were conducted among children less than 5years of age whereas the remaining studies reported on AGE among other age groups and rarely adults. In MENA countries, RV infection was reported all year round with peaks described in cold as well as hot months. This systematic review provides a current update on the epidemiology of RV-associated gastroenteritis in countries of the MENA region and draws attention to the major gaps existing in the continuous monitoring of RV.

Characterization of astrovirus-associated gastroenteritis in hospitalized children under five years of age.

PURPOSE: The aim of this study was to determine the incidence and genetic diversity of astrovirus (AstV) detected in children hospitalized for gastroenteritis (GE). METHODS: A multi-center, hospital-based surveillance study was conducted across Lebanon to investigate the incidence of AstV among diarrheal hospitalizations. Viral RNA was extracted from stool samples collected between 2011 and 2013 from children, below the age of 5years, hospitalized for GE at six medical centers across Lebanon. Demographic and clinical data were collected and analyzed. RNA of eligible samples (n=739) was screened by two AstV-specific PCR assays followed by genotype-specific PCR. Sanger sequencing and phylogenetic analysis were performed for genotypic characterization. RESULTS: Overall, 5.5% (41/739) of rotavirus-negative stool samples collected from hospitalized children <5years old tested positive for AstV infection. AstV infections were detected all year long. Diarrhea, dehydration, vomiting and fever were the most common symptoms associated with AstV infections. Children aged 48-59months had the highest incidence of AstV. Using the Vesikari Scoring System to assess clinical severity, 85.4% of children with AstV had a score>11, indicating severe GE. Genotype-specific PCR identified 22 classical and 4 MLB-like AstV specimens. Further sequencing and phylogenetic analysis of orf1b and orf2 genes revealed that AstV classical 1-3, 5, 6, and 8, MLB-1, VA-1 and -2 genotypes circulated in Lebanon. Recombination between classical AstV strains was detected in several cases as evident by the lack of congruency in the tree topologies of the orf1b and orf2. Two cases of mixed infections between classical and non-classical genotypic strains were recorded. CONCLUSION: High genetic diversity was detected among AstVs in Lebanon. AstVs are associated with 5.5% of non-rotavirus GE-associated hospitalizations in children under five years in Lebanon.