A cost-effectiveness analysis of reduced viral transmission with baloxavir marboxil versus oseltamivir or no treatment for seasonal and pandemic influenza management in the United Kingdom.

BACKGROUND: Baloxavir marboxil is an oral, single-dose, cap-dependent endonuclease inhibitor that reduces the duration of influenza symptoms and rapidly stops viral shedding. We developed a susceptible, exposed, infected, recovered (SEIR) model to inform a cost-effectiveness model (CEM) of baloxavir versus oseltamivir or no antiviral treatment in the UK. RESEARCH DESIGN AND METHODS: The SEIR model estimated the attack rates among otherwise healthy and high-risk individuals in seasonal and pandemic settings. The CEM assumed that a proportion of infected patients would receive antiviral treatment. Results were reported at the population level (per 10,000 at risk of infection). RESULTS: The SEIR model estimated greater reductions in infections with baloxavir. In a seasonal setting, baloxavir provided incremental cost-effectiveness ratios (ICERs) of £1884 per quality-adjusted life-year (QALY) gained versus oseltamivir and a dominant cost-effectiveness position versus no antiviral treatment in the total population; ICERs of £2574/QALY versus oseltamivir and £128/QALY versus no antiviral treatment were seen in the high-risk population. Baloxavir was also cost-effective versus oseltamivir or no antiviral treatment and reduced population-level health system occupancy concerns during a pandemic. CONCLUSION: Baloxavir treatment resulted in the fewest influenza cases and was cost-effective versus oseltamivir or no antiviral treatment from a UK National Health Service perspective.

Baloxavir marboxil ('baloxavir') is a prescription medicine for people who become ill with influenza (or 'the flu') that can reduce how long flu symptoms last and the likelihood of complications from the flu that may require going to the hospital. Baloxavir can also reduce the amount and duration of virus shed by infected individuals thus potentially slow or stop the flu from spreading to healthy people. We studied differences in reducing predicted flu infections between baloxavir and another flu treatment, known as oseltamivir, or no flu treatment at all. Treatment with baloxavir resulted in fewer flu infections in the UK population than oseltamivir or no treatment. We then studied how these differences might affect costs between baloxavir and oseltamivir or no treatment at a population level in the UK. Overall, in the majority of scenarios explored in the model, baloxavir was cost-effective as an antiviral treatment for people with the flu in the UK.

Airborne influenza virus shedding by patients in health care units: Removal mechanisms affecting virus transmission.

In this study, we characterize the distribution of airborne viruses (influenza A/B) in hospital rooms of patients with confirmed infections. Concurrently, we monitored fine particulate matter (PM2.5 & PM10) and several physical parameters including the room air exchange rate, temperature, and relative humidity to identify corresponding correlations with virus transport and removal determinants. The results continue to raise concerns about indoor air quality (IAQ) in healthcare facilities and the potential exposure of patients, staff and visitors to aerosolized viruses as well as elevated indoor PM levels caused by outdoor sources and/or re-suspension of settled particles by indoor activities. The influenza A virus was detected in 42% of 33 monitored rooms, with viruses detectible up to 1.5 m away from the infected patient. Active coughing was a statistically significant variable that contributed to a higher positive rate of virus detection in the collected air samples. Viral load across patient rooms ranged between 222 and 5,760 copies/m3, with a mean of 820 copies/m3. Measured PM2.5 and PM10 levels exceeded IAQ daily exposure guidelines in most monitored rooms. Statistical and numerical analyses showed that dispersion was the dominant viral removal pathway followed by settling. Changes in the relative humidity and the room's temperature were had a significant impact on the viral load removal. In closure, we highlight the need for an integrated approach to control determinants of IAQ in patients' rooms.

An update on respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections resulting in a significant burden worldwide, particularly in children and older adults. This collection calls for original research papers that advance our understanding of the epidemiology, evolution, diagnosis, clinical management, and prevention of RSV infections.

Erratum: Rotavirus Genotypes and Vaccine Effectiveness from a Sentinel, Hospital-Based, Surveillance Study for Three Consecutive Rotavirus Seasons in Lebanon.

[This corrects the article DOI: 10.1371/journal.pone.0161345.].

Vaccine evaluation and genotype characterization in children infected with rotavirus in Qatar.

BACKGROUND: We characterized and identified the genetic and antigenic variations of circulating rotavirus strains in comparison to used rotavirus vaccines. METHODS: Rotavirus-positive samples (n = 231) were collected and analyzed. The VP7 and VP4 genes were sequenced and analyzed against the rotavirus vaccine strains. Antigenic variations were illustrated on the three-dimensional models of surface proteins. RESULTS: In all, 59.7% of the hospitalized children were vaccinated, of which only 57.2% received two doses. There were no significant differences between the vaccinated and non-vaccinated groups in terms of clinical outcome. The G3 was the dominant genotype (40%) regardless of vaccination status. Several amino acid changes were identified in the VP7 and VP4 antigenic epitopes compared to the licensed vaccines. The highest variability was seen in the G3 (6 substitutions) and P[4] (11 substitutions) genotypes in comparison to RotaTeq®. In comparison to Rotarix®, G1 strains possessed three amino acid changes in 7-1a and 7-2 epitopes while P[8] strains possessed five amino acid changes in 8-1 and 8-3 epitopes. CONCLUSIONS: The current use of Rotarix® vaccine might not be effective in preventing the infection due to the higher numbers of G3-associated cases. The wide range of mutations in the antigenic epitopes compared to vaccine strains may compromise the vaccine's effectiveness. IMPACT: The reduced rotavirus vaccine effectiveness necessitate regular evaluation of the vaccine content to ensure optimal protection. We characterized and identified the genetic and antigenic variations of circulating rotavirus strains in comparison to the Rotarix vaccine strain that is used in Qatar. The study highlight the importance for regular monitoring of emerging rotavirus variants and their impact on vaccine effectiveness in young children.

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.

Viral metagenomics analysis of stool specimens from children with unresolved gastroenteritis in Qatar.

Acute gastroenteritis (AGE) is associated with significant global morbidity and mortality, especially among children under five years of age. Viruses are well established as etiologic agents of gastroenteritis since they are the most common pathogens that contribute to the disease burden in developing countries. Despite the advances in molecular diagnosis, a substantial proportion of AGE etiology remain unresolved. We implemented a viral metagenomics pipeline to determine the potential viral etiology associated with AGE among children under the age of five years in Qatar with undiagnosed etiology. Following enriching for the viral genome, ∼1.3 billion sequences were generated from 89 stool specimens using the Illumina HiSeq platform, of which 7% were mapped to viral genomes. Human viruses were detected in 34 specimens (38.2%); 14 were adenovirus, nine coxsackievirus A16, five rotavirus (G9P[8] and G4P[8]), four norovirus (GII), one influenza A virus (H3), and one respiratory syncytial virus A (RSVA). In conclusion, the viral metagenomics approach is useful for determining AGE's etiology when routine molecular diagnostic assays fail.

Neurological and Neuropsychological Changes Associated with SARS-CoV-2 Infection: New Observations, New Mechanisms.

SARS-CoV-2 infects cells through angiotensin-converting enzyme 2 (ACE2), a ubiquitous receptor that interacts with the virus' surface S glycoprotein. Recent reports show that the virus affects the central nervous system (CNS) with symptoms and complications that include dizziness, altered consciousness, encephalitis, and even stroke. These can immerge as indirect immune effects due to increased cytokine production or via direct viral entry into brain tissue. The latter is possible through neuronal access via the olfactory bulb, hematogenous access through immune cells or directly across the blood-brain barrier (BBB), and through the brain's circumventricular organs characterized by their extensive and highly permeable capillaries. Last, the COVID-19 pandemic increases stress, depression, and anxiety within infected individuals, those in isolation, and high-risk populations like children, the elderly, and health workers. This review surveys the recent updates of CNS manifestations post SARS-CoV-2 infection along with possible mechanisms that lead to them.

No association between the SARS-CoV-2 variants and mortality rates in the Eastern Mediterranean Region.

As the novel coronavirus SARS-CoV-2 continues to spread in all countries, there is a growing interest in monitoring and understanding the impact of emerging strains on virus transmission and disease severity. Here, we analyzed SARS-CoV-2 genomic sequences reported in the Eastern Mediterranean Region (EMR) countries, as of 1 January 2021. The majority (~75%) of these sequences originated from three out of 22 EMR countries, and 65.8% of all sequences belonged to GISAID clades GR, GH, G and GV. A delay ranging between 30 and 150 days from sample collection to sequence submission was observed across all countries, limiting the utility of such data in informing public health policies. We identified ten common non-synonymous mutations represented among SARS-CoV-2 in the EMR and several country-specific ones. Two substitutions, spike_D614G and NSP12_P323L, were predominantly concurrent in most countries. While the single incidence of NSP12_P323L was positively correlated with higher case fatality rates in EMR, no such association was established for the double (spike_D614G and NSP12_P323L) concurrent variant across the region. Our study identified critical data gaps in EMR highlighting the importance of enhancing surveillance and sequencing capacities in the region.

Uptake rates, knowledge, attitudes, and practices toward seasonal influenza vaccination among healthcare workers in Lebanon.

Despite recommendations and their occupational risk to influenza infection vaccine hesitancy remains a challenge among healthcare workers (HCWs). No studies have been conducted in Lebanon to assess the influenza vaccine's acceptance among HCWs. We conducted a survey to assess factors associated with vaccine uptake and practices among HCWs in Lebanon. Only 40.4% of the HCWs reported receiving the 2018-2019 seasonal vaccine and 1 out 5 routinely received the seasonal vaccine. One-third of the HCWs reported having free access to the influenza vaccine. The willingness to receive the vaccine decreased had it been offered for a fee. Self, family and community protection (55.5%) was a key vaccination enabler. While, viral evolution, concerns regarding vaccine efficacy and side effects, and cost of vaccine ranked as top vaccination barriers. The majority of the HCWs (75%) recommended the vaccine to their patients. Past influenza vaccination (Odds ratio (OR) = 2.37, CI 1.48,3.79), willingness to receive the vaccine for free (OR = 6.93, CI 4.27-11.34) or having diagnosed influenza (OR = 1.81, CI 1.12-2.92) were significantly associated with HCWs' willingness to recommend the vaccine to patients. Better knowledge about influenza and vaccination was strongly associated with the willingness to receive and recommend the vaccine (p < .001). The vaccination rate among HCWs in Lebanon was suboptimal despite the positive attitudes toward the influenza vaccine. Interventions that enhance vaccine accessibility and knowledge are warranted to improve vaccination coverage among HCWs.

The burden of Respiratory Syncytial Virus (RSV) infection in the Middle East and North Africa (MENA) region across age groups: A systematic review.

Respiratory Syncytial Virus (RSV) is a common respiratory virus that generally causes a mild illness in children and adults or severe symptoms with complications in infants and the elderly, particularly in the presence of underlying comorbidities. While epidemiological data about this virus are available globally, data from the Middle East and North Africa (MENA) region are still scarce. For this reason, we conducted a systematic review to determine the burden of RSV disease in the MENA region by searching the available literature up until September 2018. A total of 1242 studies were retrieved of which 90 were included in the review. Most of the included studies were conducted in subjects aged 0-18 years with the majority being in children below 3 years of age, while only 2 studies included exclusively adults above 18 years of age. RSV infection rates varied greatly between different studies on hospitalized subjects and ranged between 4% and 82%, while the range was smaller in studies on outpatient subjects (between 6% and 36%). When calculating the RSV infection rates in the hospitalized subjects with different inclusion criteria, we found that it was 19%, 70%, and 33% among subjects admitted with Acute Respiratory Infections (ARIs), Acute Lower Respiratory Infections (ALRIs), and bronchiolitis, respectively. RSV infections were most common during the winter season. With regards to complications, intensive care unit admissions ranged between 1% and 15%, while the need for mechanical ventilation ranged between 1% and 10%. The overall RSV related mortality rate across all age groups in studies included in our review was 1.9%. This review identifies several limitations in the existing data and under-representation of the adult population. Future studies should be providing more evidence on the RSV burden in adults and children with comorbidities in order to better assess the potential impact of future preventive strategies in the MENA region.

Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities.

As of January 2021, SARS-CoV-2 has killed over 2 million individuals across the world. As such, there is an urgent need for vaccines and therapeutics to reduce the burden of COVID-19. Several vaccines, including mRNA, vector-based vaccines, and inactivated vaccines, have been approved for emergency use in various countries. However, the slow roll-out of vaccines and insufficient global supply remains a challenge to turn the tide of the pandemic. Moreover, vaccines are important tools for preventing the disease but therapeutic tools to treat patients are also needed. As such, since the beginning of the pandemic, repurposed FDA-approved drugs have been sought as potential therapeutic options for COVID-19 due to their known safety profiles and potential anti-viral effects. One of these drugs is ivermectin (IVM), an antiparasitic drug created in the 1970s. IVM later exerted antiviral activity against various viruses including SARS-CoV-2. In this review, we delineate the story of how this antiparasitic drug was eventually identified as a potential treatment option for COVID-19. We review SARS-CoV-2 lifecycle, the role of the nucleocapsid protein, the turning points in past research that provided initial 'hints' for IVM's antiviral activity and its molecular mechanism of action- and finally, we culminate with the current clinical findings.

Epidemiological, molecular, and clinical features of rotavirus infections among pediatrics in Qatar.

Acute gastroenteritis (AGE) remains a major cause of diarrhea in developing and developed countries. Rotavirus (RV) is a leading cause of severe pediatric diarrhea worldwide. Here we report on the prevalence of circulating genotypes in association with demographics and clinical manifestations outcomes in Qatar. A total of 231 RV-positive fecal samples were collected from children suffering from AGE during 3 years study period between June 2016 and June 2019. The age of the subjects ranged between 2 months and 14 years (median of 16 months). The VP4 and VP7 were amplified and sequenced. Phylogenetic analyses were performed using MEGA7.0. Pearson's chi-squared test was used to determine significant differences for comparisons of general categorical variables. RV infections were most common in children between 1 and 3 years of age (49%), followed by those < 1 year and > 3 years of age (33% and 28%, respectively). RV infections were more frequent in males than females, with a ratio of 1.4:1. RV infections occurred throughout the year, with a noticeable increase in summer (42.8%) and a drop in winter (20.1%). RV genotypes G3P[8] (30.8%), G2P[8] (12.3%), G4P[8] (11.7%), and G1P[8] (10.4%) were the common genotypes during the study period. The G3P[8] strain detected in our study revealed similarities to the equine-like G3P[8] (10.3%; 24/231) (KT988229.1), Wa-like genomic constellation (9%; 21/231) (MF563894.1), and DS-1-like strains (6.4%; 15/231) (LC386081.1). Based on the Vesikari score system, severe clinical illness including diarrhea and vomiting (average frequency: 4 to 5 times/day) was recorded for G3P[8] group, followed by G9P[8], G4P[8], and G1P[8]. Higher incidence for G3P[8], G2P[8], G4P[8], and G1P[8] were reported in Qatari subjects compared to other nationalities. The multinational status of a small country explains the wide diversity of circulating RV genotypes in Qatar. The highest prevalence and severe illnesses were recorded to G3P[8], which is different from other surrounding countries/global levels.

The origins of G12P[6] rotavirus strains detected in Lebanon.

The G12 rotaviruses are an increasingly important cause of severe diarrhoea in infants and young children worldwide. Seven human G12P[6] rotavirus strains were detected in stool samples from children hospitalized with gastroenteritis in Lebanon during a 2011-2013 surveillance study. Complete genomes of these strains were sequenced using VirCapSeq-VERT, a capture-based high-throughput viral-sequencing method, and further characterized based on phylogenetic analyses with global RVA and vaccine strains. Based on the complete genomic analysis, all Lebanese G12 strains were found to have Wa-like genetic backbone G12-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1. Phylogenetically, these strains fell into two clusters where one of them might have emerged from Southeast Asian strains and the second one seems to have a mixed backbone between North American and Southeast Asian strains. Further analysis of these strains revealed high antigenic variability compared to available vaccine strains. To our knowledge, this is the first report on the complete genome-based characterization of G12P[6] emerging in Lebanon. Additional studies will provide important insights into the evolutionary dynamics of G12 rotaviruses spreading in Asia.

Three-Dimensional Cell Culture Models to Study Respiratory Virus Infections Including COVID-19.

Respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are among the most common illnesses and a leading cause of morbidity and mortality worldwide. Due to the severe effects on health, the need of new tools to study the pathogenesis of respiratory viruses as well as to test for new antiviral drugs and vaccines is urgent. In vitro culture model systems, such as three-dimensional (3D) cultures, are emerging as a desirable approach to understand the virus host interactions and to identify novel therapeutic agents. In the first part of the article, we address the various scaffold-free and scaffold-based 3D culture models such as hydrogels, bioreactors, spheroids and 3D bioprinting as well as present their properties and advantages over conventional 2D methods. Then, we review the 3D models that have been used to study the most common respiratory viruses including influenza, parainfluenza, respiratory syncytial virus (RSV) and coronaviruses. Herein, we also explain how 3D models have been applied to understand the novel SARS-CoV-2 infectivity and to develop potential therapies.