The Impact of eHealth Technologies on the Management Process of the Surgical Treatment of Obesity during the COVID-19 Pandemic (preprint)

(1) Introduction: The COVID-19 pandemic presented unique challenges for patients and healthcare providers, especially for those working with obesity and related health problems. E-health has emerged as a crucial tool for the follow-up of users undergoing bariatric surgery during this period, allowing remote monitoring of users' health status and providing access to virtual consultation with health professionals. This study aims to analyze the impact of the use of telemedicine during the COVID-19 pandemic on the results of bariatric surgery and user satisfac-tion with this follow-up. (2) Method: Observational study with retrospective data collection. The variables were divided into several groups: health data, associated comorbidities, quality of life, quality of sleep and satisfaction with telemedicine monitoring. (3) Results: Surgery significantly affected weight loss, in general more than 75% loss of excess weight. Comorbidities, like the qual-ity of life, were reversed over time, with 50% of subjects maintaining excellent levels. Although most users were satisfied with the monitoring, the variables had no relationship. (4) Conclusions: The follow-up assured by telemedicine did not alter the results of bariatric surgery, which may allow us to infer that it may be an option to consider for regular monitoring of the post-bariatric surgery process.

Long COVID in Children and Adolescents: A Retrospective Controlled Cohort Study from Iran (preprint)

Background: After recovering from the acute phase of COVID-19, some of the infected children manifest long COVID symptoms. The present study aims to identify long COVID symptoms in children and adolescents admitted to hospitals in Bushehr, Iran, during 2021 to 2023, and compare them with the non-affected group. Methods: This retrospective cohort study was conducted on 141 children and adolescents with COVID-19 and 141 non-affected peers. The data were collected using the data recorded in the patients’ records, conducting telephone interviews and completing the prevalent long COVID symptom form. Results: The mean age of the hospitalized children with COVID-19 was 79±5.24 months old, 57.4% of whom were boys. Also, 46 individuals of the infected group (32.6%) manifested long COVID symptoms. The most prevalent symptoms included fatigue (54.3%), impaired attention or concentration (41.3%) and depression or anxiety symptoms (34.7%). Significant correlation was found between disease severity and muscle and joint pain (P=0.025) as well as between length of hospital stay and cough (P=0.022), weight loss (P=0.047) and depression or anxiety symptoms (P=0.008). Older age [(6-11 y; OR=3.18, CI=1.03-9.88); (12≥ y; OR= 4.57, CI=1.40-14.96)] and having history of smoking or being exposed to secondhand smoke (OR= 12.45, CI= 3.14-49.36) were considered as risk factors for long COVID. Conclusions: Informing the public about smoking or being exposed to smoke as risk factors for long COVID, in addition to its other hazards, is of particular importance. Informing the healthcare staff and general public about the most prevalent symptoms of long COVID could be effective in timely diagnosis and treatment as well as reducing families’ stress burden.

Efficacy of Host Cell Serine Protease Inhibitor MM3122 against SARS-CoV-2 for Treatment and Prevention of COVID-19 (preprint)

We have developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases including TMPRSS2, matriptase and hepsin. TMPRSS2 is a membrane associated protease which is highly expressed in the upper and lower respiratory tract and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell receptor binding, entry, replication, and dissemination of new virion particles. We have previously shown that compound MM3122 exhibited subnanomolar potency against all three proteases and displayed potent antiviral effects against SARS-CoV-2 in a cell-viability assay. Herein, we demonstrate that MM3122 potently inhibits viral replication in human lung epithelial cells and is effective against the XBB.1.5 and EG.5.1 variant of SARS-CoV-2. Further, we have evaluated MM3122 in a mouse model of COVID-19 and have demonstrated that MM3122 administered intraperitoneally (IP) before (prophylactic) or after (therapeutic) SARS-CoV-2 infection had significant protective effects against weight loss and lung congestion, and reduced pathology. Amelioration of COVID-19 disease was associated with a reduction in pro-inflammatory cytokines and chemokines production after SARS-CoV-2 infection. Prophylactic, but not therapeutic, administration of MM3122 also reduced virus titers in the lungs of SARS-CoV-2 infected mice. Therefore, MM3122 is a promising lead candidate small molecule drug for the treatment and prevention of infections caused by SARS-CoV-2 and other coronaviruses.

Few-shot learning for COVID-19 Chest X-Ray Classification with Imbalanced Data: An Inter vs. Intra Domain Study (preprint)

Medical image datasets are essential for training models used in computer-aided diagnosis, treatment planning, and medical research. However, some challenges are associated with these datasets, including variability in data distribution, data scarcity, and transfer learning issues when using models pre-trained from generic images. This work studies the effect of these challenges at the intra- and inter-domain level in few-shot learning scenarios with severe data imbalance. For this, we propose a methodology based on Siamese neural networks in which a series of techniques are integrated to mitigate the effects of data scarcity and distribution imbalance. Specifically, different initialization and data augmentation methods are analyzed, and four adaptations to Siamese networks of solutions to deal with imbalanced data are introduced, including data balancing and weighted loss, both separately and combined, and with a different balance of pairing ratios. Moreover, we also assess the inference process considering four classifiers, namely Histogram, $k$NN, SVM, and Random Forest. Evaluation is performed on three chest X-ray datasets with annotated cases of both positive and negative COVID-19 diagnoses. The accuracy of each technique proposed for the Siamese architecture is analyzed separately and their results are compared to those obtained using equivalent methods on a state-of-the-art CNN. We conclude that the introduced techniques offer promising improvements over the baseline in almost all cases, and that the selection of the technique may vary depending on the amount of data available and the level of imbalance.

A Murine Model of Post-acute Neurological Sequelae Following SARS-CoV-2 Variant Infection (preprint)

Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. Surviving mice showed no detectable viral RNA in the brain and minimal neuroinflammation post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and reduced levels of genes associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent T helper 1 prone cellular immune responses and high neutralizing antibodies against Delta and Omicron variants in the periphery for months post-acute infection. Overall, infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long COVID patients and may be useful for future assessment of the efficacy of vaccines and therapeutics against SARS-CoV-2 variants.

Multi-target mode of action of Sulfodyne(R), a stabilized Sulforaphane, against pathogenic effects of SARS-CoV-2 infection (preprint)

The coronavirus disease 2019 (COVID-19) due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown that, except vaccination, few therapeutics options for its treatment or prevention are available. Among the pathways that can be targeted for COVID-19 treatment, the Keap1/Nrf2 pathway seems of high interest as it regulates redox homeostasis and inflammation that are altered during SARS-CoV-2 infection. Here, we use three potent activators of the Keap1/Nrf2 pathway and showed that Sulfodyne(R), a stabilized natural Sulforaphane preparation with optimal bioavailability, had the highest antiviral activity in pulmonary or colonic epithelial cell lines even when added late after SARS-CoV-2 infection. This antiviral activity was not dependent on NRF2 activity but associated with action on ER stress and mTOR signaling that are activated during SARS-CoV-2 infection. Sulfodyne(R) also decreased the inflammatory response of epithelial cell lines infected by SARS-CoV-2 independently of SARS-CoV-2 replication and reduced the activation of human monocytes that are recruited after infection of epithelial cells by SARS-CoV-2. Administration of Sulfodyne(R) had little effects on SARS-CoV-2 replication in mice and hamsters infected with SARS-CoV-2 but significantly reduced weight loss and disease severity. Altogether, these results pinpoint the natural compound Sulfodyne(R) as a potent therapeutic agent of COVID-19 symptomatology.

A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines (preprint)

Continuous evolution of SARS-CoV-2 alters the antigenicity of the immunodominant spike (S) receptor-binding domain and N-terminal domain, undermining the efficacy of vaccines and monoclonal antibody therapies. To overcome this challenge, we set out to develop a vaccine focusing antibody responses on the highly conserved but metastable S2 subunit, which folds as a spring-loaded fusion machinery. Here, we describe a protein design strategy enabling prefusion-stabilization of the SARS-CoV-2 S2 subunit and high yield recombinant expression of trimers with native structure and antigenicity. We demonstrate that our design strategy is broadly generalizable to all sarbecoviruses, as exemplified with the SARS-CoV-1 (clade 1a) and PRD-0038 (clade 3) S2 fusion machineries. Immunization of mice with a prefusion-stabilized SARS-CoV-2 S2 trimer vaccine elicits broadly reactive sarbecovirus antibody responses and neutralizing antibody titers of comparable magnitude against Wuhan-Hu-1 and the immune evasive XBB.1.5 variant. Vaccinated mice were protected from weight loss and disease upon challenge with SARS-CoV-2 XBB.1.5, providing proof-of-principle for fusion machinery sarbecovirus vaccines motivating future development.

SARS-CoV-2 induces acute neurological signs while Calcitonin Gene-Related Peptide (CGRP) signaling blockade reduces interleukin 6 (IL-6) release and weight loss in mouse models (preprint)

COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. We evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 CGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. We determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking CGRP. These findings suggest that blockage of CGRP signaling protects against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection.

Sarbecovirus disease susceptibility is conserved across viral and host models (preprint)

Coronaviruses have caused three severe epidemics since the start of the 21st century: SARS, MERS and COVID-19. The severity of the ongoing COVID-19 pandemic and increasing likelihood of future coronavirus outbreaks motivates greater understanding of factors leading to severe coronavirus disease. We screened ten strains from the Collaborative Cross mouse genetic reference panel and identified strains CC006/TauUnc (CC006) and CC044/Unc (CC044) as coronavirus-susceptible and resistant, respectively, as indicated by variable weight loss and lung congestion scores four days post-infection. We generated a genetic mapping population of 755 CC006xCC044 F2 mice and exposed the mice to one of three genetically distinct mouse-adapted coronaviruses: clade 1a SARS-CoV MA15 (n=391), clade 1b SARS-CoV-2 MA10 (n=274), and clade 2 HKU3-CoV MA (n=90). Quantitative trait loci (QTL) mapping in SARS-CoV- and SARS-CoV-2-infected F2 mice identified genetic loci associated with disease severity. Specifically, we identified seven loci associated with variation in outcome following infection with either virus, including one, HrS45, that is present in both groups. Three of these QTL, including HrS45, were also associated with HKU3-CoV MA outcome. HrS45 overlaps with a QTL previously reported by our lab that is associated with SARS-CoV outcome in CC011xCC074 F2 mice and is also syntenic with a human chromosomal region associated with severe COVID-19 outcomes in humans GWAS. The results reported here provide: (a) additional support for the involvement of this locus in SARS-CoV MA15 infection, (b) the first conclusive evidence that this locus is associated with susceptibility across the Sarbecovirus subgenus, and (c) demonstration of the relevance of mouse models in the study of coronavirus disease susceptibility in humans.

Change in body weight of older adults before and during the COVID-19 pandemic: Longitudinal results from the Berlin Aging Study II (preprint)

Background: Change in body weight during the COVID-19 pandemic as an unintended side effect of lockdown measures has been predominantly reported for younger and middle-aged adults. However, information on older adults for which weight loss is known to result in adverse outcomes, is scarce. Aims: Describe body weight change in older adults before, during, and after the COVID-19 lockdown measures and explore putative associated factors with a focus on the period that includes the first six months of the COVID-19 containment measures. Methods: In this study, we analyzed the longitudinal weight change of 472 participants of the Berlin Aging Study II (mean age of 67.5 years at baseline, average follow-up time 10 years). Additionally, differences between subgroups characterized by socio-economic, cognitive, and psychosocial variables as well as morbidity burden, biological age markers (epigenetic clocks, telomere length), and frailty were compared. Results: On average, women and men lost 0.87% (n=227) and 0.5% (n=245) of their body weight per year in the study period covering the first six months of the COVID-19 pandemic. Weight loss among men was particularly pronounced among groups characterized by change in physical activity due to COVID-19 lockdown, low positive affect, premature epigenetic age (7-CpG clock), diagnosed metabolic syndrome, and a more masculine gender score (all variables: p<0.05, n=245). Conclusions: Older participants lost weight with a 2.5-times (women) and 2-times (men) higher rate than what is expected in this age.

SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression (preprint)

The virus severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, is the causative agent of the current COVID-19 pandemic. It possesses a large 30 kilobase (kb) genome that encodes structural, non-structural, and accessory proteins. Although not necessary to cause disease, these accessory proteins are known to influence viral replication and pathogenesis. Through the synthesis of novel infectious clones of SARS-CoV-2 that lack one or more of the accessory proteins of the virus, we have found that one of these accessory proteins, ORF8, is critical for the modulation of the host inflammatory response. Mice infected with a SARS-CoV-2 virus lacking ORF8 exhibit increased weight loss and exacerbated macrophage infiltration into the lungs. Additionally, infection of mice with recombinant SARS-CoV-2 viruses encoding ORF8 mutations found in variants of concern reveal that naturally occurring mutations in this protein influence disease severity. Our studies with a virus lacking this ORF8 protein and viruses possessing naturally occurring point mutations in this protein demonstrate that this protein impacts pathogenesis.

No evidence for enhanced disease with polyclonal SARS-CoV-2 antibody in the ferret model. (preprint)

Since SARS-CoV-2 emerged in late 2019, it spread from China to the rest of the world. An initial concern was the potential for vaccine- or antibody-enhanced disease (AED) as had been reported with other coronaviruses. To evaluate this, we first developed a ferret model by exposing ferrets to SARS-CoV-2 by either mucosal inoculation (intranasal/oral) or inhalation using a small particle aerosol. Mucosal inoculation caused a mild fever and weight loss that resolved quickly; inoculation via either route resulted in virus shedding detected in the nares, throat, and rectum for 7-10 days post-infection. To evaluate the potential for AED, we then inoculated groups of ferrets intravenously with 0.1, 0.5, or 1 mg/kg doses of a human polyclonal anti-SARS-CoV-2 IgG from hyper-immunized transchromosomic bovines (SAB-185). Twelve hours later, ferrets were challenged by mucosal inoculation with SARS-CoV-2. We found no significant differences in fever, weight loss, or viral shedding after infection between the three antibody groups or the controls. Signs of pathology in the lungs were noted in infected ferrets but no differences were found between control and antibody groups. The results of this study indicate that healthy, young adult ferrets of both sexes are a suitable model of mild COVID-19 and that low doses of specific IgG in SAB-185 are unlikely to enhance the disease caused by SARS-CoV-2.

Recombinant SARS-CoV-2 lacking initiating and internal methionine codons within ORF10 is attenuated in vivo (preprint)

SARS-CoV-2 has been proposed to encode ORF10 as the 3' terminal gene in the viral genome. However, the potential role and even existence of a functional ORF10 product has been the subject of debate. There are significant structural features in the viral genomic RNA that could, by themselves, explain the retention of the ORF10 nucleotide sequences without the need for a functional protein product. To explore this question further we made two recombinant viruses, firstly a control virus (WT) based on the genome sequence of the original Wuhan isolate and with the inclusion of the early D614G mutation in the Spike protein. We also made a second virus, identical to WT except for two additional changes that replaced the initiating ORF10 start codon and an internal methionine codon for stop codons (ORF10KO). Here we show that the two viruses have apparently identical growth kinetics in a VeroE6 cell line that over expresses TMPRSS2 (VTN cells). However, in A549 cells over expressing ACE2 and TMPRSS2 (A549-AT cells) the ORF10KO virus appears to have a small growth rate advantage. Growth competition experiments were used whereby the two viruses were mixed, passaged in either VTN or A549-AT cells and the resulting output virus was sequenced. We found that in VTN cells the WT virus quickly dominated whereas in the A549-AT cells the ORF10KO virus dominated. We then used a hamster model of SARS-CoV-2 infection and determined that the ORF10KO virus has attenuated pathogenicity (as measured by weight loss). We found an almost 10-fold reduction in viral titre in the lower respiratory tract for ORF10KO vs WT. In contrast, the WT and ORF10KO viruses had similar titres in the upper respiratory tract. Sequencing of viral RNA in the lungs of hamsters infected with ORF10KO virus revealed that this virus frequently reverts to WT. Our data suggests that the retention of a functional ORF10 sequence is highly desirable for SARS-CoV-2 infection of hamsters and affects the virus's ability to propagate in the lower respiratory tract.

Efficacy of the oral nucleoside prodrug GS-5245 (Obeldesivir) against SARS-CoV-2 and coronaviruses with pandemic potential (preprint)

Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, the emergence of SARS-CoV-2 variants of concern (VOC) that can partially evade vaccine immunity remains a global health concern. In addition, the emergence of highly mutated and neutralization-resistant SARS-CoV-2 VOCs such as BA.1 and BA.5 that can partially or fully evade (1) many therapeutic monoclonal antibodies in clinical use underlines the need for additional effective treatment strategies. Here, we characterize the antiviral activity of GS-5245, Obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved RNA-dependent viral RNA polymerase (RdRp). Importantly, we show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-related Bat-CoV RsSHC014, Middle East Respiratory Syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant in vitro and highly effective as antiviral therapy in mouse models of SARS-CoV, SARS-CoV-2 (WA/1), MERS-CoV and Bat-CoV RsSHC014 pathogenesis. In all these models of divergent coronaviruses, we observed protection and/or significant reduction of disease metrics such as weight loss, lung viral replication, acute lung injury, and degradation in pulmonary function in GS-5245-treated mice compared to vehicle controls. Finally, we demonstrate that GS-5245 in combination with the main protease (Mpro) inhibitor nirmatrelvir had increased efficacy in vivo against SARS-CoV-2 compared to each single agent. Altogether, our data supports the continuing clinical evaluation of GS-5245 in humans infected with COVID-19, including as part of a combination antiviral therapy, especially in populations with the most urgent need for more efficacious and durable interventions.

Partially hydrolyzed guar gum attenuates the symptoms of SARS-CoV-2 infection through gut microbiota modulation in an animal model. (preprint)

The coronavirus disease 2019 (COVID-19) pandemic has caused worldwide health issues. Although several vaccines have been developed, it is still difficult to prevent and reduce the inflammation caused by the infection. Studies have shown that there are correlations between the gut environment and severity of symptoms caused by SARS-CoV-2 infection. Several gut metabolites produced by the gut microbiota such as SCFAs and the secondary bile acid UDCA are reported to improve the survival rate of the host after viral infection in an animal model through modulation of the host immune system. Therefore, in this study, we attempted to use the prebiotic dietary fiber PHGG to modulate the gut microbiome and intestinal metabolites for improvement of host survival rate after SARS-CoV-2 infection in a Syrian hamster model. We were able to show that PHGG significantly improved the host survival rate and body weight reduction. Analysis of the gut microbiome, serum, and intestinal metabolites revealed that PHGG significantly increased the concentrations of several intestinal SCFAs, fecal secondary bile acids, and serum secondary bile acids. Furthermore, several microbial species and metabolites identified in this study are consistent with reports in humans. Taken together, our data suggest that PHGG is a candidate prebiotic food for reducing the morbidity of COVID-19.

Anti-Viral and Anti-Inflammatory Therapeutic Effect of RAGE-Ig Protein Against Multiple SARS-CoV-2 Variants of Concern Demonstrated in K18-hACE2 Mouse and Syrian Golden Hamster Models (preprint)

Significance: SARS-CoV-2 Variants of Concern (VOCs) continue to evolve and re-emerge with chronic inflammatory long-COVID sequelae necessitating the development of anti-inflammatory therapeutic molecules. Therapeutic effects of the Receptor for Advanced Glycation End products (RAGE) were reported in many inflammatory diseases. However, a therapeutic effect of the RAGE in COVID-19 has not been reported. In the present study, we investigated whether and how the RAGE-Ig fusion protein would have an anti-viral and anti-inflammatory therapeutic effect in the COVID-19 system. Methods: The protective therapeutic effect of RAGE-Ig was determined in vitro in K18-hACE2 transgenic mice and Syrian golden hamsters infected with six various VOCs of SARS-CoV-2. The underlying anti-viral mechanism of RAGE-Ig was determined in vitro in SARS-CoV-2-infected human lung epithelial cells (BEAS-2B). Results: Following treatment of K18-hACE2 mice and hamsters infected with various SARS-CoV-2 VOCs with RAGE-Ig, we demonstrated: (i) significant dose-dependent protection (i.e. greater survival, less weight loss, lower virus replication in the lungs); (ii) a reduction of inflammatory macrophages (F4/80+/Ly6C+) and neutrophils (CD11b+/Ly6G+) infiltrating the infected lungs; (iii) a RAGE-Ig dose-dependent increase in the expression of type I interferons (IFN-alpha;, and IFN-beta) and type III interferon (IFN lambda2) and a decrease in the inflammatory cytokines (IL-6 and IL-8) in SARS-CoV-2-infected human lung epithelial cells; and (iv) a dose-dependent decrease in the expression of CD64 (FcgR1) on monocytes and lung epithelial cells from symptomatic COVID-19 patients. Conclusion: Our pre-clinical findings revealed type I and III interferons-mediated anti-viral and anti-inflammatory therapeutic effects of RAGE-Ig protein against COVID-19 caused by multiple SARS-CoV-2 VOCs.

Effectiveness and cost-effectiveness of text messages with or without endowment incentives for weight management in men with obesity (Game of Stones): study protocol for a randomised controlled trial.

BACKGROUND: Obesity increases the risk of type 2 diabetes, heart disease, stroke, mobility problems and some cancers, and its prevalence is rising. Men engage less than women in existing weight loss interventions. Game of Stones builds on a successful feasibility study and aims to find out if automated text messages with or without endowment incentives are effective and cost-effective for weight loss at 12 months compared to a waiting list comparator arm in men with obesity. METHODS: A 3-arm, parallel group, assessor-blind superiority randomised controlled trial with process evaluation will recruit 585 adult men with body mass index of 30 kg/m2 or more living in and around three UK centres (Belfast, Bristol, Glasgow), purposively targeting disadvantaged areas. Intervention groups: (i) automated, theory-informed text messages daily for 12 months plus endowment incentives linked to verified weight loss targets at 3, 6 and 12 months; (ii) the same text messages and weight loss assessment protocol; (iii) comparator group: 12 month waiting list, then text messages for 3 months. The primary outcome is percentage weight change at 12 months from baseline. Secondary outcomes at 12 months are as follows: quality of life, wellbeing, mental health, weight stigma, behaviours, satisfaction and confidence. Follow-up includes weight at 24 months. A health economic evaluation will measure cost-effectiveness over the trial and over modelled lifetime: including health service resource-use and quality-adjusted life years. The cost-utility analysis will report incremental cost per quality-adjusted life years gained. Participant and service provider perspectives will be explored via telephone interviews, and exploratory mixed methods process evaluation analyses will focus on mental health, multiple long-term conditions, health inequalities and implementation strategies. DISCUSSION: The trial will report whether text messages (with and without cash incentives) can help men to lose weight over 1 year and maintain this for another year compared to a comparator group; the costs and benefits to the health service; and men's experiences of the interventions. Process analyses with public involvement and service commissioner input will ensure that this open-source digital self-care intervention could be sustainable and scalable by a range of NHS or public services. TRIAL REGISTRATION: ISRCTN 91974895 . Registered on 14/04/2021.

Developing survey weights to ensure representativeness in a national, matched cohort study: results from the Children and young people with Long Covid (CLoCk) study. (preprint)

Background: Findings from studies assessing Long Covid in children and young people (CYP) need to be viewed in light of their methodological limitations. For example, if non-response and/or attrition over time systematically differ by sub-groups of CYP, findings could be biased and generalisation limited. The present study aimed to (i) construct survey weights for the Children and young people with Long Covid (CLoCk) study, and (ii) apply them to published CLoCk findings showing the prevalence of shortness of breath and tiredness increased over time from baseline to 12-months post-baseline in both SARS-CoV-2 Positive and Negative CYP. Methods: Logistic regression was used to compute the probability of (i) Responding given envisioned to take part, (ii) Responding timely given responded, and (iii) (Re)infection given timely response. Response, timely response and (re)infection weights were generated as the reciprocal of the corresponding probability, with an overall ‘envisioned population’ survey weight derived as the product of these weights. Survey weights were trimmed, and an interactive tool developed to re-calibrate target population survey weights to the general population using data from the 2021 UK Census. Results: Flexible survey weights for the CLoCk study were successfully developed. In the illustrative example re-weighted results (when accounting for selection in response, attrition, and (re)infection) were consistent with published findings. Conclusions: Flexible survey weights to address potential bias and selection issues were created for and used in the CLoCk study. Previously reported prospective findings from CLoCk are generalisable to the wider population of CYP in England. This study highlights the importance of considering selection into a sample and attrition over time when considering generalisability of findings.

Single-anastomosis Sleeve Jejunal: a Mid-term Follow-up Report of a New Surgical Technique.

INTRODUCTION: Single anastomosis sleeve ileal bypass (SASI) is a combined bariatric metabolic technique, in which few studies have shown its outcomes efficacy. However, this technique has a high risk of malnutrition due to long biliopancreatic limb. Single anastomosis sleeve jejunal bypass (SASJ) has a shorter limb. Therefore, it seems to have a lower risk of nutrient deficiency. Furthermore, this technique is relatively new, and little is known about the efficacy and safety of SASJ. We aim to report our mid-term follow-up of SASJ from a high-volume center for bariatric metabolic surgery in the Middle East region. METHODS: For the current study, the 18-month follow-up data of 43 patients with severe obesity who underwent SASJ was collected. The primary outcome measures were demographic data, weight change variables according to ideal body mass index (BMI) of 25 kg/m2 at 6, 12, and 18 months, laboratory assessments, remission of obesity-associated medical problems, and other potential bariatric metabolic complications after the surgery. RESULTS: No patient was lost due to follow-up. After 18 months, patients lost 43.4 ± 11 kg of their weight and 68 ± 14% of their excess weight, and their BMI decreased from 44.9 ± 4.7 to 28.6 ± 3.8 kg/m2 (p < 0.001). The percentage of total weight loss till 18 months was 36.3%. The T2D remission rate at 18 months was 100%. Patients neither faced deficiency in significant markers for nutrition state nor represented major bariatric metabolic surgery complications. CONCLUSION: SASJ bypass achieved satisfactory weight loss and remissions in obesity-associated medical problems within 18 months after surgery without major complications and malnutrition.

Gender differences in individuals with obesity and binge eating disorder: A retrospective comparison of phenotypical features and treatment outcomes.

OBJECTIVE: Phenotypical comparisons between individuals with obesity without binge eating disorder (OB) and individuals with obesity and comorbid binge eating disorder (OB + BED) are subject to ongoing investigations. At the same time, gender-related differences have rarely been explored, raising the question whether men and women with OB and OB + BED may require differently tailored treatments. METHOD: We retrospectively compared pre- versus post-treatment data in a matched sample of n = 180 men and n = 180 women with OB or OB + BED who received inpatient treatment. RESULTS: We found that men displayed higher weight loss than women independent of diagnostic group. In addition, men with OB + BED showed higher weight loss than men with OB after 7 weeks of treatment. CONCLUSIONS: The present findings add to an emerging yet overall still sparse body of studies comparing phenotypical features and treatment outcomes in men and women with OB and OB + BED; implications for further research are discussed. CLINICAL TRIAL REGISTRATION: The study was prospectively registered with the German Clinical Trial Register as part of application DRKS00028441.