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Abstract Background Ethiopia’s National Malaria Control and Elimination Program aims to diagnose all suspected malaria cases within 24 h of fever onset and provide prompt treatment for confirmed cases. This study explored psychosocial factors associated with no-, delayed- and prompt- care-seeking among female caregivers of children under five years with fever in rural Ethiopia. Methods Household surveys were conducted from 2016–2019 among female caregivers (N = 479) of children under five years old with fever in Oromia; Amhara; Southern Nations, Nationalities, and Peoples Region (SNNPR); and Tigray. Prompt and delayed care-seeking were defined as seeking treatment within ≤ 24 h or > 24 h of symptom onset respectively. Contextual factors explored included sociodemographic factors, household supply of bed nets, exposure to health messages, and household vulnerability (a measure of financial access to food, shelter, schooling, and medical treatment). Ideational factors included psychosocial factors related to care-seeking (knowledge, self-efficacy, response efficacy, attitudes, involvement in decision-making, and household social support). Results The prevalence of fever among children under five years was 18% (ranging from 9% in Tigray to 34% in SNNPR. Overall, 45% of caregivers of children with fever sought care promptly, while 23% delayed care-seeking and 32% sought no care. Prompt care-seeking rates were higher among caregivers with positive attitudes toward prompt care-seeking (48%), involved in decision-making (48%) or perceived equitable gender norms in the community (65%). Caregivers with a high care-seeking ideation had increased odds of prompt care-seeking (aOR: 2.65; 95% CI: 1.74–4.02). Significant contextual factors included residence in the Oromia region (aOR: 2.99; 95% CI:1.40–6.41), caregivers age 35–49 years (aOR: 0.49; 95% CI: 0.26–0.95), residence in vulnerable households (aOR: 2.01; 95% CI: 1.28–3.18). Conclusions Among this rural Ethiopian population, prompt care-seeking was low but positively influenced by both ideational and contextual psychosocial factors occurring at the caregiver level. Multi-sectoral interventions at the individual, community, and health facility levels are needed to improve prompt care-seeking. These include social behavior change interventions to improve ideation, complemented by health facility interventions to ensure provision of high-quality services and structural interventions to increase educational attainment in these rural settings.

Plain Language summary A reproductive health study involving mixed quantitative and qualitative methods was conducted in Ethiopia in 2016–2017. The overall objectives of the study are (1) to use mixed methods research to identify determinants of contraceptive use in four regions of Ethiopia, and (2) to explore the relationship between social norms, gender equitable norms, couple communication, and contraceptive use. The survey identified gender inequitable norms as a major barrier to contraceptive use. The qualitative study further examined the gender dimension and the interlinkages between gender norms, couple communication, and decision making for contraceptive use. Data showed that gender norms related to the daily living dimension of the gender equitable men (GEM) scale are significantly associated with current contraceptive use. The qualitative component provides us with in-depth data on the daily experiences of rural Ethiopian women in the context of modern contraceptive use. We learned that social norms related to the desired number of children and the timing of first contraceptive use are interlinked. Specifically, both women and men told us that most couples do not use contraceptives until their family size is complete, after 4–5 children. Similarly, couples who opt for 2 or fewer children are termed “selfish” and “not interested in children.” Couple communication occurs within the context of decision making where men’s decisions are usually accepted, and women’s decisions are often deferred or rejected. Programs should promote respect for women’s decision-making abilities and equitable couple communication. Notably, this study finds that microprocesses of couple communication and decision making are gendered, featuring female disadvantage. Further research is required on these microprocesses of gendered couple communication.

Abstract Background Evidence on process outcomes such as acceptability, and feasibility of behavior change communication interventions are important in program evaluation to understand how, and why such a program works. However; documented evidence on the issue is not available as far as the social and behavior change communication (SBCC) on malaria is concerned. Enrolling the frontline providers this study measured the acceptability and feasibility of the school-engaged SBCC strategy on malaria prevention in malaria-endemic settings of Ethiopia. Methods A school-engaged SBCC strategy involving various communication and capacity-building interventions aimed to advance malaria preventive practices in primary schools in Jimma were implemented from 2017 to 2019. A cross-sectional study was conducted with 205 key stakeholders at the end of the intervention. Both acceptability and feasibility were measured using standardized tools. Data were collected using a structured questionnaire and filled by the study participants. The SPSS version 26 was used to analyze the data. Multivariate general linear modeling was performed to identify the predictors of acceptability and feasibility of the program. P-value

Abstract Background The engagement of schools in malaria control is an emerging strategy. Little is known about the involvement of students in the development of malaria messages. This study evaluated the message content of primary school students’ malaria poems. Methods A qualitative content analysis was conducted to explore malaria messages conveyed in poems produced by students. Twenty poems were purposively selected from twenty schools across rural villages in five districts of the Jimma Zone. Data were analyzed using Atlas.ti version 7.1.4 software. The message contents were quantified in terms of frequency, and including metaphors, presented using central themes, categories, and supportive quotations. Results A total of 602 malarial contents were generated, and organized into 21 categories under five central themes. 1) Malaria-related knowledge (causation and modes of transmission, mosquito breeding and biting behavior, signs and symptoms, care for insecticide-treated nets (ITNs), and prevention methods), 2) Perceived threats from malaria, 3)The effectiveness of prevention methods (i.e., related to the adaption of ITNs, environmental cleaning, indoor residual spray (IRS), treatment for fever, and drug adherence practices), 4) Misconceptions, beliefs, and malpractices regarding the cause of malaria and drug use) and 5) Direct calls to the adopt ITN, IRS, clean surroundings, treatment, and drug use. The most commonly conveyed message contents were about the severity of malaria, distinguishable signs and symptoms, calls for community participation for malaria elimination, knowledge of preventive methods, and effectiveness of ITN use. Metaphoric expressions (war and death) were used to convey messages about the severity and the need to manage the prognosis of malaria through the active ITN use, which itself was metaphorically represented as ‘a trap’ to mosquitoes. Conclusions The poetic analysis indicated that the students developed and disseminated rich malarial messages, especially on malarial knowledge, and perceptions, beliefs, norms and practices of the local community to prevent and control malaria. Therefore, primary school students can be a source of information and would effectively communicate knowledge, perceptions, and promote malaria related practices, particularly in rural settings.

Abstract Background Insecticide-treated nets (ITNs) access-use has been pivotal monitoring indicator for malaria prevention and control, particularly in resource limited settings. The objective of the study was to compare ITN access-use based on universal household and population indicators and measures adapted to sleeping spaces. Methods A cross-sectional study was conducted in five districts of Jimma Zone, Ethiopia, March, 2019. 762 HHs were sampled for the survey. Multi-stage followed by simple random sampling used. Monitoring and evaluation reference group’s (MERG’s) indicators were used for measuring ITN access-use. MERG’s indicators are each adapted ITN access-use to sleeping spaces. Household (ownership, saturation and sufficiency) and population access and household members’ status of last night sleeping under ITN compared based on the two models. Differences of estimates of ITN access-use based on the two methods reported as magnitude of over/under estimations, at p-value 2 people actually slept per sleeping space. Conclusions MERG’s universal indicators over estimated households and populations ITN access-use as a result of absence of measures capturing access-use values at spaces where people actually slept. Consequently, measures adapted to sleeping contexts revealed potential misdistributions practiced when the existing indicators are in use. Insertion of sleeping spaces into existing approach will be worthwhile and needs to be promoted as it improves curiosity in ITN distribution, produces closer estimates and prevents malaria prevention and control programmes from overlooking access-use challenges.

Abstract Background Evidence on what makes the school-engaged social and behavior change communication (SBCC) interventions on malaria prevention more sustainable are limited in literature partly due to its recent emergence. Enrolling the key stakeholders, this study explored the perceived sustainability of the SBCC interventions on malaria prevention through primary school communities in rural Ethiopia. Methods The SBCC interventions were implemented from 2017 to 2019 in 75 primary schools and villages in rural Jimma to promote malaria preventive practices. As a part of program evaluation, this study employed a mixed-method to collect qualitative and quantitative data from 205 stakeholders following the end of the program. Data were collected using interview guides and structured questionnaires. The SPSS version 26 and Atlas ti7.1 software were used to analyze the data. Multivariable linear regression modeling was used to identify predictors of the perceived sustainability of the program (SOP). Results The mean score of SOP was 25.93 (SD = 4.32; range 6–30). Multivariable linear regression modeling showed that the perceived risk to malaria (β = 0.150; P = 0.029), self-efficacy (β = 0.192; P = 0.003), and perceived fidelity of implementation (β = 0.292; P = 0.000) and degree of adoption (β = 0.286; P = 0.000) were positively predicted the perceived SOP. The qualitative result identified various barriers and opportunities to sustaining the program that summarized under three themes which include perceptions about the quality of program delivery (e.g inadequate involvement of stakeholders and staffs, concerns over short project life, immature sustainability efforts), school settings (e.g schools’ malaria priority, schools’ climate and quality of coaching) and the outer settings (e.g existing structures in the health and education systems). Conclusion The study identified key predictive variables such as stakeholders’ perceived risk to malaria, self-efficacy, perceived fidelity of implementation and degree of adoption that could help to improve the sustainment of the school-based SBCC approach on malaria prevention and control. Further longitudinal study should be conducted to examine the rate of decline in program components over time and how improved sustainability would contribute to the effectiveness on malaria preventive behaviors among students.

Abstract Background School-based behaviour change communication interventions could help to achieve behavioural changes in the school and enhance the enrollment of the students and teachers as health messengers to local communities. Evidence on the impacts of the school-engaged malaria preventive interventions are limited as far as the social and behaviour change communication (SBCC) is concerned. This study examined the effectiveness of the school-based SBCC approach on insecticide-treated nets (ITNs) utilization among primary school students in malaria-endemic settings of Ethiopia. Methods Various participatory, educational, and communication interventions were implemented from 2017 to 2019 in 75 primary schools and respective villages in Jimma to promote malaria preventive practices. A quasi-experimental design was conducted with randomly selected 798 students (i.e. 399 intervention and 399 control groups). Data were collected by trained interviewers using structured questionnaires. The SPSS version 26 software was used to analyse the data. Propensity score matching analysis was performed to control for possible confounding biases. The average effects of the intervention were estimated using multivariate general linear modelling to estimate for mean differences and odds ratio based on the nature of data. Results The result showed that the ITNs utilization was 6.857 folds in the intervention groups compared to the counterpart; (OR = 6.857; 95% CI: (4.636, 10.1430); effect size = 39%). A mean differences (MD) of self-efficacy (MD = 15.34; 95% CI: 13.73 to 16.95), knowledge (MD = 5.83; 95% CI: 5.12 to 6.55), attitude (MD = 6.01; 95% CI: 5.26 to 6.77), perceived malaria risk (MD = 2.14; 95% CI: 1.53 to 2.76), and perceived family supports (MD = 6.39; 95% CI: 5.57 to 7.22) were observed favoring the intervention. Multivariable logistic regression modelling results showed that knowledge (β = 0.194, 95% CI: 1.09 to 1.35) and perceived family supports (β = 0.165, 95% CI: 1.11 to 1.25) and self-efficacy (β = 0.10, 95% CI: 1.22 to 2.32) predicted the ITN utilization among the school children. Conclusions The finding of this study suggested that the school-based SBCC approach combined with peer education activities advanced the malaria-related knowledge, attitude, self-efficacy, risk perceptions, and family supports and ultimately improved the sustained use of ITNs among school-going children. Further research should be conducted to understand the mechanism of these effects given the influences of social, health services, and school systems are considered.

Abstract Background Making insecticide-treated nets (ITNs) utilization a social norm would support the global goal of malaria eradication and Ethiopian national aim of its elimination by 2030. Jimma zone is one of the endemic settings in Ethiopia. This study aimed to report effects of malaria education, delivered by students, on community behaviours; particularly ITNs. Methods In pre-posttest, cross-sectional household surveys conducted in rural villages of 5 districts in Jimma Zone, Ethiopia, 762 households were sampled. The intervention engaged students from primary schools in participatory peer education within small groups, followed by exposing parents with malaria messages aimed at influencing perceptions and practices. The data were analysed using SPSS version 20.0. Proportions/means differences were computed to compare changes in exposure, knowledge, perceptions, and practices using 95% CI at p

BackgroundEthiopia has shown incredible success in malaria morbidity, mortality, and control. Community empowerment is a milestone to meet the ambitious plans of eliminating malaria by 2030.ObjectivesThis study aimed to evaluate school-based malaria social behavior change communication (SBCC) in terms of community message exposure, acceptance, knowledge, and practices.MethodsA community-based pre-posttest study was conducted in five districts of the Jimma Zone, Ethiopia. 762 and 759 households were sampled for baseline and end-line, respectively. The intervention engaged students from primary schools on participatory peer education within small groups, followed by exposing parents with malaria messages aimed to influencing ideation and preventive practices. The data were analyzed using Statistical Package for Social Sciences (SPSS) version 20.0. Proportion/mean differences were computed to compare both surveys on exposure, knowledge, perceptions, and practices at p ResultsThe study revealed a sharp increase in exposure to malaria messages with effect size (ES) of 65.7%, p ConclusionsEngaging school-aged children effectively advances community exposure, perception, and behaviors. We recommend the inclusion of school-based SBCC in the national malaria control programs.

Abstract Background Laryngeal injury associated with traumatic or prolonged intubation may lead to voice, swallow, and airway complications. The interplay between inflammation and microbial population shifts induced by intubation may relate to clinical outcomes. The objective of this study was to investigate laryngeal mechanics, tissue inflammatory response, and local microbiome changes with laryngotracheal injury and localized delivery of therapeutics via drug-eluting endotracheal tube. Methods A simulated traumatic intubation injury was created in Yorkshire crossbreed swine under direct laryngoscopy. Endotracheal tubes electrospun with roxadustat or valacyclovir- loaded polycaprolactone (PCL) fibers were placed in the injured airway for 3, 7, or 14 days (n = 3 per group/time and ETT type). Vocal fold stiffness was then evaluated with normal indentation and laryngeal tissue sections were histologically examined. Immunohistochemistry and inflammatory marker profiling were conducted to evaluate the inflammatory response associated with injury and ETT placement. Additionally, ETT biofilm formation was visualized using scanning electron microscopy and micro-computed tomography, while changes in the airway microbiome were profiled through 16S rRNA sequencing. Results Laryngeal tissue with roxadustat ETT placement had increasing localized stiffness outcomes over time and histological assessment indicated minimal epithelial ulceration and fibrosis, while inflammation remained severe across all timepoints. In contrast, vocal fold tissue with valacyclovir ETT placement showed no significant changes in stiffness over time; histological analysis presented a reduction in epithelial ulceration and inflammation scores along with increased fibrosis observed at 14 days. Immunohistochemistry revealed a decline in M1 and M2 macrophage markers over time for both ETT types. Among the cytokines, IL-8 levels differed significantly between the roxadustat and valacyclovir ETT groups, while no other cytokines showed statistically significant differences. Additionally, increased biofilm formation was observed in the coated ETTs with notable alterations in microbiota distinctive to each ETT type and across time. Conclusion The injured and intubated airway resulted in increased laryngeal stiffness. Local inflammation and the type of therapeutic administered impacted the bacterial composition within the upper respiratory microbiome, which in turn mediated local tissue healing and recovery.

Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic bacteria frequently linked to burn wound infections. These bacteria can grow as biofilms, which increases their level of drug resistance to current antibiotics. The purpose of the present study is to analyze the effect of biofilm formation, phage and phage cocktail action on single species and dual species biofilms I, e the coexistence of Gram positive (S. aureus) and Gram negative (P. aeruginosa). To this scenario, we employed multi-drug resistant bacteria (P. aeruginosa and S. aureus at 109 CFU/µL) biofilm as single and in combination of both Gram-positive and Gram-negative bacterial biofilms of 24 h grown with respective phage (109 PFU/µL) and phage cocktail (109 PFU/µL) at 4 h of incubation under static conditions. The bacteriolytic activity of phages vB_SAnS_SADP1 and vB_PAnP_PADP4 on 24-h-old biofilms of P. aeruginosa (0.761 ± 0.031) and S. aureus (0.856 ± 0.055), both alone and in combination (0.67 ± 0.02), was the focus of this investigation. The structural organization of biofilms in single- or dual-species combinations under in vitro conditions was validated by scanning and confocal laser scanning microscopy investigations. After 24 h of incubation, single-species biofilms are denser and more resilient whereas dual species biofilms are more loosely associated. Loose association of dual-species biofilm under scanning electron microscopic images at the same conditions, indicated the interspecies -competition of the Gram-positive and Gram-negative bacteria and dual-species biofilms (0.67 ± 0.02) have weak associations and are readily impacted by phage and a phage cocktail (0.16 ± 0.02). Dual-species biofilms were more readily impacted in in vitro settings.

Hard X-ray absorption spectroscopy is a valuable in situ probe for non-destructive diagnostics of metal sites. The low-energy interval of a spectrum (XANES) contains information about the metal oxidation state, ligand type, symmetry and distances in the first coordination shell but shows almost no dependency on the bridged metal–metal bond length. The higher-energy interval (EXAFS), on the contrary, is more sensitive to the coordination numbers and can decouple the contribution from distances in different coordination shells. Supervised machine-learning methods can combine information from different intervals of a spectrum; however, computational approaches for the near-edge region of the spectrum and higher energies are different. This work aims to keep all benefits of XANES and extend its sensitivity towards the interatomic distances in the first and second coordination shells. Using a binuclear bridged copper complex as a case study and cross-validation analysis as a quantitative tool it is shown that the first 170 eV above the edge are already sufficient to balance the contributions of Cu–O/N scattering and Cu–Cu scattering. As a more general outcome this work highlights the trivial but often overlooked importance of using `longer' energy intervals of XANES for structural refinement and machine-learning predictions. The first 200 eV above the absorption edge still do not require parametrization of Debye–Waller damping and can be calculated within full multiple scattering or finite difference approximations with only moderately increased computational costs.

Background: The clinical frailty scale (CFS) was used as a triage tool for medical decision making during the COVID-19 pandemic. The CFS has been posed as a suitable risk marker for in-hospital mortality in COVID-19 patients. We evaluated whether the CFS is associated with mortality 24 months after hospitalisation for COVID-19. Methods: The COvid MEdicaTion (COMET) study is an international, multicentre, observational cohort study, including adult patients hospitalised for COVID-19 between March 2020–July 2020. Patients’ characteristics, prescribed medication, clinical characteristics, and CFS were collected at admission, survival data were collected 24 months after hospitalisation. Multivariable cox proportional hazard models stratified by age (

Prompt care seeking and appropriate use of anti-malarial drugs are critical components of malaria prevention and control. This study assessed malaria related perceptions, care seeking behavior and anti-malarial drug use in malaria endemic settings of Ethiopia.Data were generated from a community based cross-sectional study conducted among 798 households during January 2014 as part of a larger household behavioral study in three malaria endemic districts of Jimma Zone, Southwest Ethiopia. Both quantitative and qualitative data were collected and analyzed using SPSS 17.0 and STATA 12.0.In this study, only 76.1% of the respondents associated malaria to mosquito bite, and incorrect beliefs and perceptions were noted. Despite moderate level of knowledge (estimated mean = 62.2, Std Err = 0.7, 95% CI: 60.6-63.8%), quite high favorable attitude (overall estimated mean = 91.5, Std Err = 0.6, 95% CI: 90.1-92.9%) were recorded towards malaria preventive measures. The mean attitude score for prompt care seeking, appropriate use of anti-malarial drugs, LLIN use and Indoor Residual Spray acceptance was 98.5 (Std Err = 0.4, 95% CI:97.5-99.4), 92.7 (Std Err = 0.6 95% CI:91.5-93.9), 88.8 (Std Err = 0.5, 95% CI:85.5-92.1) and 86.5 (Std Err = 1.2, 95% CI: 83.9-89.1), respectively. The prevalence of fever was 2.9% (116/4107) and of the study participants with fever, 71.9% (95% CI: 65.5-78.3%) sought care and all of them consulted formal health care system. However, only 17 (19.8%) sought care within 24 hours after onset of fever. The frequency of care seeking was higher (77.8%, n = 21/27) and more prompt (28.6%, 6/21) for children under five as compared to old age groups despite it was not statistically significant (p > 0.05). However, higher median time of seeking first care was observed among Muslims and people who did not attend school (p < 0.05). Of those who used anti-malarial drugs, 9.1% indicated that they used it inappropriately through saving and/or sharing. Irregular availability of anti-malarial drugs; irregular presence of frontline health workers and misconceptions were mentioned to contribute to delayed care seeking and irrational use of anti-malarial drugs.Although care seeking behavior for febrile illness was quite high in this community, the habit of prompt care seeking was very limited. Thus, malaria prevention and control programs need to take into account local misconceptions and wrong perceptions, and health system factors to achieve optimal health seeking behavior in such malaria endemic settings.

Glioblastoma multiforme (GBM) is one of the most aggressive tumors known to occur in the brain. Metabolism is one of the driving factors enabling the successful proliferation of tumor cells, thus increasing the tumor mass. Tumor metabolism is now recognized as a major hallmark of oncogenesis. Since the brain largely relies on its glucose supply for growth, glucose metabolism significantly contributes to oncogenesis in brain cancers. Here, we review the major metabolic pathways seen in normal brain physiology in addition to the Warburg effect, aberrant tricarboxylic acid cycle, and oxidative phosphorylation observed in GBM. We highlight the important differences in glucose metabolism between the normal and cancerous environments. In addition, we provide insights into lactate shuttling, the pentose phosphate pathway, and immune interactions with glucose metabolism, which drive the nutritional pathways in both the normal and cancerous environment.

Abstract While poly(ethylene glycol) (PEG) hydrogels are generally regarded as biologically inert blank slates, concerns over PEG immunogenicity are growing, and the implications for tissue engineering are unknown. Here, we investigate these implications by immunizing mice against PEG to stimulate anti-PEG antibody production and evaluating bone defect regeneration after treatment with bone morphogenetic protein-2-loaded PEG hydrogels. Quantitative analysis reveals that PEG sensitization increases bone formation compared to naive controls, whereas histological analysis shows that PEG sensitization induces an abnormally porous bone morphology at the defect site, particularly in males. Furthermore, immune cell recruitment is higher in PEG-sensitized mice administered the PEG-based treatment than their naive counterparts. Interestingly, naive controls that were administered a PEG-based treatment also develop anti-PEG antibodies. Sex differences in bone formation and immune cell recruitment are also apparent. Overall, these findings indicate that anti-PEG immune responses can impact tissue engineering efficacy and highlight the need for further investigation.

BackgroundEnvironmental lipopolysaccharide (LPS) and microbial component-enriched organic dusts cause significant lung disease. These environmental exposures induce the recruitment and activation of distinct lung monocyte/macrophage subpopulations involved in disease pathogenesis. Aconitate decarboxylase 1 (Acod1) was one of the most upregulated genes following LPS (vs. saline) exposure of murine whole lungs with transcriptomic profiling of sorted lung monocyte/macrophage subpopulations also highlighting its significance. Given monocyte/macrophage activation can be tightly linked to metabolism, the objective of these studies was to determine the role of the immunometabolic regulator ACOD1 in environmental exposure-induced lung inflammation.MethodsWild-type (WT) mice were intratracheally (i.t.) instilled with 10 μg of LPS or saline. Whole lungs were profiled using bulk RNA sequencing or sorted to isolate monocyte/macrophage subpopulations. Sorted subpopulations were then characterized transcriptomically using a NanoString innate immunity multiplex array 48 h post-exposure. Next, WT and Acod1−/− mice were instilled with LPS, 25% organic dust extract (ODE), or saline, whereupon serum, bronchoalveolar lavage fluid (BALF), and lung tissues were collected. BALF metabolites of the tricarboxylic acid (TCA) cycle were quantified by mass spectrometry. Cytokines/chemokines and tissue remodeling mediators were quantitated by ELISA. Lung immune cells were characterized by flow cytometry. Invasive lung function testing was performed 3 h post-LPS with WT and Acod1−/− mice.ResultsAcod1−/− mice treated with LPS demonstrated decreased BALF levels of itaconate, TCA cycle reprogramming, decreased BALF neutrophils, increased lung CD4+ T cells, decreased BALF and lung levels of TNF-α, and decreased BALF CXCL1 compared to WT animals. In comparison, Acod1−/− mice treated with ODE demonstrated decreased serum pentraxin-2, BALF levels of itaconate, lung total cell, neutrophil, monocyte, and B-cell infiltrates with decreased BALF levels of TNF-α and IL-6 and decreased lung CXCL1 vs. WT animals. Mediators of tissue remodeling (TIMP1, MMP-8, MMP-9) were also decreased in the LPS-exposed Acod1−/− mice, with MMP-9 also reduced in ODE-exposed Acod1−/− mice. Lung function assessments demonstrated a blunted response to LPS-induced airway hyperresponsiveness in Acod1−/− animals.ConclusionAcod1 is robustly upregulated in the lungs following LPS exposure and encodes a key immunometabolic regulator. ACOD1 mediates the proinflammatory response to acute inhaled environmental LPS and organic dust exposure-induced lung inflammation.

Summary: Delta (B.1.617.2) and Omicron (B.1.1.529) variants of SARS-CoV-2 represents unique clinical characteristics. However, their role in altering immunometabolic regulations during acute infection remains convoluted. Here, we evaluated the differential immunopathogenesis of Delta vs. Omicron variants in Golden Syrian hamsters (GSH). The Delta variant resulted in higher virus titers in throat swabs and the lungs and exhibited higher lung damage with immune cell infiltration than the Omicron variant. The gene expression levels of immune mediators and metabolic enzymes, Arg-1 and IDO1 in the Delta-infected lungs were significantly higher compared to Omicron. Further, Delta/Omicron infection perturbed carbohydrates, amino acids, nucleotides, and TCA cycle metabolites and was differentially regulated compared to uninfected lungs. Collectively, our data provide a novel insight into immunometabolic/pathogenic outcomes for Delta vs. Omicron infection in the GSH displaying concordance with COVID-19 patients associated with inflammation and tissue injury during acute infection that offered possible new targets to develop potential therapeutics.