Repurposing of poly-gamma-glutamic acid, immunotherapeutic drug for cervical intraepithelial neoplasia 1, as covid-19 treatment

Covid-19 virus variants identified so far are due to viral genetic diversity, genetic evolution, and variable infectivity, suggesting that high infection rates and high mortality rates may be contributed by these mutations. And it has been reported that the targeting strategies for innate immunity should be less vulnerable to viral evolution, variant emergence and resistance. Therefore, the most effective solution to Covid-19 infection has been proposed to prevent and treat severe exacerbation of patients with moderate disease by enhancing human immune responses such as NK cell and T cell. In previous studies, we demonstrated for the first time that gamma-PGA induced significant antitumor activity and antiviral activity by modulating NK cell-mediated cytotoxicity. Especially intranasal administration of gamma-PGA was found to effectively induce protective innate and CTL immune responses against viruses and we found out that gamma-PGA can be an effective treatment for cervical intraepithelial neoplasia 1 through phase 2b clinical trial. In this study, the possibility of gamma-PGA as a Covid-19 immune modulating agent was confirmed by animal experiments infected with Covid-19 viruses. After oral administration of gamma-PGA 300mug/mouse once a day for 5 days in a K18-hACE2 TG mouse model infected with SARS-CoV-2 (NCCP 43326;original strain) and SARS-CoV-2 (NCCP 43390;Delta variant), virus titer and clinical symptom improvement were confirmed. In the RjHan:AURA Syrian hamster model infected with SARS-CoV-2 (NCCP 49930;Delta variant), 350 or 550 mug/head of gamma-PGA was administered orally for 10 days once a day. The virus for infection was administered at 5 x 104 TCID50, and the titer of virus and the improvement of pneumonia lesions were measured to confirm the effectiveness in terms of prevention or treatment. In the mouse model infected with original Covid-19 virus stain, the weight loss was significantly reduced and the survival rate was also improved by the administration of gamma-PGA. And gamma-PGA alleviated the pneumonic lesions and reduced the virus titer of lung tissue in mice infected with delta variant. In the deltavariant virus infected hamster model, gamma-PGA showed statistically significant improvement of weight loss and lung inflammation during administration after infection. This is a promising result for possibility of Covid-19 therapeutics along with the efficacy results of mouse model, suggesting gammaPGA can be therapeutic candidate to modulate an innate immune response for Covid-19.

Scalability of digital psychological innovations for refugees: A comparative analysis in Egypt, Germany, and Sweden

E-mental health interventions may offer innovative means to increase access to psychological support and improve the mental health of refugees. However, there is limited knowledge about how these innovations can be scaled up and integrated sustainably into routine services. This study examined the scalability of a digital psychological intervention called Step-by-Step (SbS) for refugees in Egypt, Germany, and Sweden. We conducted semi-structured interviews (n = 88) with Syrian refugees, and experts in SbS or mental health among refugees in the three countries. Data collection and analysis were guided by a system innovation perspective. Interviewees identified three contextual factors that influenced scalability of SbS in each country: increasing use of e-health, the COVID-19 pandemic, and political instability. Nine factors lay at the interface between the innovation and potential delivery systems, and these were categorised by culture (ways of thinking), structure (ways of organising), and practice (ways of doing). Factors related to culture included: perceived need and acceptability of the innovation. Acceptability was influenced by mental health stigma and awareness, digital trust, perceived novelty of self-help interventions, and attitudes towards non-specialist (e-helper) support. Factors related to structure included financing, regulations, accessibility, competencies of e-helpers, and quality control. Factors related to practice were barriers in the initial and continued engagement of end-users. Many actors with a potential stake in the integration of SbS across the three countries were identified, with nineteen stakeholders deemed most powerful. Several context-specific integration scenarios were developed, which need to be tested. We conclude that integrating novel e-mental health interventions for refugees into routine services will be a complex task due to the many interrelated factors and actors involved. Multi-stakeholder collaboration, including the involvement of end-users, will be essential.

Social Contacts and Compliance with SARS-CoV-2 Distancing Measures in the First Lockdown 2020 among Refugees from Syria and Afghanistan in Vienna

The article deals with the impact of the SARS-CoV-2 pandemic and related measures on the social interactions of refugees from Afghanistan and Syria in Vienna during the first lockdown in March/April 2020. The focus is on the challenges for these vulnerable groups in the field of tension between the contact minimisation prescribed in the Corona regulations of the federal government on the one hand and cramped housing conditions, precarious labour market positions, homeschooling and the "digital divide” on the other. Further focal points are how refugees deal with the measures of "social/physical distancing”, its consequences in view of the colliding cultural norms, the extent of contact reduction and its causal factors. The empirical basis was provided by a quantitative online survey and qualitative interviews with refugees as well as experts from refugee support NGOs and organisations from both groups of origin, who were involved in the underlying project within the framework of a community-based participatory approach. Contrasting with the criticism sometimes voiced in the media that primarily certain groups with a migration background have been less compliant with the measures to contain the pandemic, a more differentiated picture is drawn. Above all, the factors of family status, age and housing conditions have had a strong influence on compliance with the distancing measures. The inaccessibility of public space, which is a particularly important resource for the refugees, as well as the discontinuation of social services offered by NGOs have particularly affected these vulnerable groups. © 2022 Austrian Geographical Society. All rights reserved.

Ethnic Reflections of the Global Outbreak: A Multi-Dimensional Examination on Syrian Refugees and Settlements in the First Phase of the Coronavirus Outbreak

This study aims to examine the effects of the coronavirus pan-demic on Syrian refugees at the neighbourhood level within the framework of perceptions, personal protection experiences, economic and social structure, and practices of neighbourhood usage. The major data source of this qualitative study included in-depth interviews with Syrian refugees living in Ulubey-Onder Neighbourhoods (Ankara). The findings displayed the effects of the pandemic on Syrians and their settlements, and a compari-son before and after the outbreak. The study demonstrated that the effective information sources of Syrians are composed of so-cial and communicational networks, and social media platforms. Their religious beliefs and social and economic needs both shape their perception on not being contaminated, and explain their reaction towards and resistance to respect the measures of the outbreak. Their lack of knowledge on available health services, attitudes of ignoring the use of face masks and social distanc-ing rules, family structures, and living and working conditions in-crease the risk of the spread of the virus. Although the crowded streets proved that human movement and commercial vitality in Syrian settlements continue as it was before the pandemic, the family incomes and standards of living diminished due to laid offs and limited access to donations of NGOs. This led to empowerment of solidarity networks and social relations in the area. Additionally, this study found out both gender differences in socialization opportunities, and negative effects of curfews and suspension of congregational praying activities on social life dur-ing pandemic times.

"Actionable" host genetic markers for repurposing "add-on therapy" in COVID-19

Background/Objectives: COVID-19 still represents a lifethreatening disease in individuals with a specific genetic background. We successfully applied a new Machine Learning method on WES data to extract a set of coding variants relevant for COVID- 19 severity. We aim to identify personalized add-on therapy. Method(s): A subset of identified variants, "actionable" by repurposed drugs, were functionally tested by in vitro and in vivo experiments. Result(s): Males with either rare loss of function variants in the TLR7 gene or L412F polymorphism in the TLR3 gene benefit from IFN-gamma, which is specifically defective in activated PBMCs, restoring innate immunity. Females heterozygous for rare variants in the ADAMTS13 gene and males with D603N homozygous polymorphism in the SELP gene benefit from Caplacizumab, which reduces vWF aggregation and thrombus formation. Males with either the low-frequency gain of function variant T201M in CYP19A1 gene or with poly-Q repeats >=23 in the AR gene benefit from Letrozole, an aromatase inhibitor, which restores normal testosterone levels, reducing inflammation and which rescues male golden hamsters from severe COVID-19. Conclusion(s): By adding these commonly used drugs to standard of care of selected patients, the rate of intubation is expected to decrease consistently, especially in patients with high penetrance rare genetic markers, mitigating the effect of the pandemic with a significant impact on the healthcare system.

COVID-associated pernio: Mechanistic insights to an abortive, seronegative SARS-CoV-2 infection

Introduction: SARS-CoV-2 replicates primarily in the airways but generates a systemic immune response mediated by Type I interferons (IFN-I). Pernio is a rare skin manifestation of disorders characterized by excessive IFN-I signalling. Although pernio increased in incidence during the pandemic, the relationship to SARS-CoV-2 remains controversial. Because of the pivotal nature of interferons in COVID-19 outcomes, pernio offers a window to investigate the biology underlying host resiliency to SARS-CoV-2 infection. Method(s): To further assess COVID-associated pernio, we characterized clinical samples from affected patients across 4 waves of the pandemic and investigated mechanistic feasibility in a rodent model. Patients were followed longitudinally with banking of blood and tissue. Golden hamsters were mock-treated or intra-nasally infected with SARS-CoV-2 and harvested at 3-and 30-days post-infection. Result(s): In affected tissue, immunophenotyping utilizing multiplex immunohistochemistry profiled a robust IFN-1 signature characterized by plasmacytoid dendritic cell activation. Viral RNA was detectable in a subset of cases using in situ hybridization for the SARS-CoV-2 S gene transcript. Profiling of the systemic immune response did not reveal a durable type 1 interferon signature. Consistent with previous literature, antibody and T-cell specific responses to SARS-CoV-2 were not detected. Nasopharyngeal SARS-CoV-2 inoculation in hamsters resulted in rapid dissemination of viral RNA and the generation of an IFN-I response that were both detectable in the paws of infected animals. Conclusion(s): Our data support a durable local IFN signature, with direct evidence of viral SARS-CoV-2 RNA in acral skin and suggest that COVID-associated pernio results from an abortive, seronegative SARS-CoV-2 infection.

The Omicron Sub-Variant BA.4 Displays a Remarkable Lack of Clinical Signs in a Golden Syrian Hamster Model of SARS-CoV-2 Infection.

The ongoing emergence of SARS-CoV-2 virus variants remains a source of concern because it is accompanied by the potential for increased virulence as well as evasion of immunity. Here we show that, although having an almost identical spike gene sequence as another Omicron variant (BA.5.2.1), a BA.4 isolate lacked all the typical disease characteristics of other isolates seen in the Golden Syrian hamster model despite replicating almost as effectively. Animals infected with BA.4 had similar viral shedding profiles to those seen with BA.5.2.1 (up to day 6 post-infection), but they all failed to lose weight or present with any other significant clinical signs. We hypothesize that this lack of detectable signs of disease during infection with BA.4 was due to a small (nine nucleotide) deletion (∆686-694) in the viral genome (ORF1ab) responsible for the production of non-structural protein 1, which resulted in the loss of three amino acids (aa 141-143).

The Highly Conserved Stem-Loop II Motif Is Dispensable for SARS-CoV-2.

The stem-loop II motif (s2m) is an RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over 25 years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion. Deletion or mutation of the s2m had no effect on growth in vitro or on growth and viral fitness in Syrian hamsters in vivo. We also compared the secondary structure of the 3' UTR of wild-type and s2m deletion viruses using selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) and dimethyl sulfate mutational profiling and sequencing (DMS-MaPseq). These experiments demonstrate that the s2m forms an independent structure and that its deletion does not alter the overall remaining 3'-UTR RNA structure. Together, these findings suggest that s2m is dispensable for SARS-CoV-2. IMPORTANCE RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), contain functional structures to support virus replication, translation, and evasion of the host antiviral immune response. The 3' untranslated region of early isolates of SARS-CoV-2 contained a stem-loop II motif (s2m), which is an RNA structural element that is found in many RNA viruses. This motif was discovered over 25 years ago, but its functional significance is unknown. We created SARS-CoV-2 with deletions or mutations of the s2m and determined the effect of these changes on viral growth in tissue culture and in rodent models of infection. Deletion or mutation of the s2m element had no effect on growth in vitro or on growth and viral fitness in Syrian hamsters in vivo. We also observed no impact of the deletion on other known RNA structures in the same region of the genome. These experiments demonstrate that s2m is dispensable for SARS-CoV-2.

Evaluation of Efficacy of the Amino Acid-Peptide Complex Administered Intragastrically to Golden Hamsters Experimentally Infected with Sars-Cov-2

The development of coronavirus infection outbreak into a pandemic, coupled with the lack of effective COVID-19 therapies, is a challenge for the entire pharmaceutical industry. This study aimed to assess the treatment and preventive efficacy of the amino acid-peptide complex (APC) in male Syrian hamsters infected with SARSCoV-2 (intranasal administration of 26 mul of the virus culture, titer of 4 x 104 TCD50/ml). In a modeled COVID-19 case, APC administered for treatment and preventive purposes reduced lung damage. Compared to the positive control group, test group had the lung weight factor 15.2% smaller (trend), which indicates a less pronounced edema. Microscopic examination revealed no alveolar edema, atypical hypertrophied forms of type II alveolocytes, pulmonary parenchyma fibrinization. The macrophage reaction intensified, which is probably a result of the APC-induced activation of regenerative processes in the lung tissues. Spleens of the animals that received APC for therapeutic and preventive purposes were less engorged and had fewer hemorrhages. The decrease of body weight of the test animals that received APC for treatment and prevention was insignificant (p < 0.05), which indicates a less severe course of COVID-19. Administered following a purely therapeutic protocol, APC proved ineffective against SARS-CoV-2 post-infection. Thus, APC-based drug used as a therapeutic and preventive agent reduces pulmonary edema and makes morphological signs of lung tissue damage less pronounced in male Syrian hamsters infected with SARS-CoV-2.Copyright © Extreme Medicine.All right reserved.

Experimental and Clinical Evaluation of Mefloquine Effectiveness against the Infection Caused by Sars-Cov-2

The efficacy of mefloquine has not been studied in the in vivo experiments and clinical trials involving COVID-19 patients. The study was aimed to assess the effects of mefloquine on the SARS-CoV-2 accumulation in the lungs of infected animals and to study the efficacy and safety of mefloquine compared to hydroxychloroquine in patients with COVID-19. During the experiment, a total of 96 Syrian hamsters were infected with SARS-CoV-2. Accumulation of the virus in lungs was compared in the groups of animals treated with mefloquine and ribavirin and in the control group. During the clinical trial, the mefloquine and hydroxychloroquine safety and efficacy in patients with mild and moderate COVID-19 (172 individuals) was assessed based on the symptom changes over time and the computed tomography results. The experiment showed that the SARS-CoV-2 accumulation in the lungs of Syrian hamsters 6 days after infection and mefloquine treatment was 2.2 +/- 0.18 lg PFU/g, which was lower (p < 0.05) than in the control group (3.5 +/- 0.21 lg PFU/g) and ribavirin group (5.2 +/- 0.05 lg PFU/g). During the clinical trial, it was found that 50.0% of patients in the mefloquine group and 32.4% in the hydroxychloroquine group (p < 0.05) developed a mild disease, and the completely resolved respiratory failure was registered in 76.5% and 44.6%, respectively (p < 0.001). Adverse events were observed in 86.7 % and 77% of patients in the mefloquine and hydroxychloroquine groups, respectively (p > 0.05). Thus, during the experiment, mefloquine contributed to the faster virus titer reduction in the lungs. During the clinical trial, the mefloquine efficacy was non-inferiority or, based on a number of indicators, higher compared to hydroxychloroquine, with comparable safety.Copyright © Extreme Medicine.All right reserved.

The Impact of Covid-19 Pandemic on Food and Nutrition Security and Dietary Habits Among Syrian Refugees in Camps: A General Review

With over one billion people experiencing nutritional shortages, food insecurity is expanding as a worldwide problem. There are presently 657,628 Syrian refugees registered in Jordan nine years after the crisis in the Syrian Arab Republic began. The COVID-19 pandemic had a substantial impact on pregnant women, nursing mothers, and most families with small children regarding food and nutrition security. It affected refugees worldwide. This review focuses on Syrian refugees' nutritional intake and the factors influencing their dietary habits, eating habits, and food insecurity. Due to system interdependencies, these impacts have cascaded across different components of the humanitarian aid provision system and led to risks of deterred personal growth and longer-term risks on the future leadership of the refugee community. The methodology followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A structured search of two databases-PubMed and Google Scholar—was carried out, and articles were identified that focused upon the impact of COVID-19 pandemic on food and nutrition security and dietary habits among refugees in camps. From this study, we recommend devising an interdisciplinary framework for assessing the education, protection, food security and household needs of the refugee communities together rather than intervening discreetly, and using the food security and household component of the system as the ladder to achieve effective management of pandemic-borne risks for the community. © 2023 The Author(s). Published by Enviro Research Publishers.

Nirmatrelvir and Molnupiravir Coadministration Modifies Preclinical Viral Exposure

Background: Implementation of vaccination programmes has had a transformational impact on control of the SARS-CoV-2 pandemic, but the need for effective antiviral drugs remains. Molnupiravir (MPV) targets viral RNA polymerase inhibiting replication via lethal mutagenesis and nirmatrelvir (NTV) is a protease inhibitor boosted with ritonavir when given clinically. This study aimed to assess the virological efficacy of NTV and MPV individually and in combination against the SARS-CoV-2 BA.1 Omicron variant in a K18-hACE2 mouse model. Method(s): K18-hACE2 mice were inoculated intranasally with 103 PFU of SARSCoV-2 BA.1 Omicron (B.1.1.529). After 24 hours, mice were orally dosed q12H, as outlined in Figure 1. At 2, 3, and 4-days post infection mice were sacrificed, and lung samples harvested. Animals were weighed and monitored daily throughout. Subsequently, viral replication in the lung was quantified using qRT-PCR to measure total (N-gene) and sub-genomic (E-gene) viral RNA. Data were normalized to 18S for quantitation. Viral exposures expressed as Areas Under viral load Curves (AUCs) were calculated by the trapezoidal method using mean values at each timepoint. Separate studies in Syrian golden hamsters using individual drugs were also conducted, and total serum IgG was measured by ELISA at 4-days post infection. Result(s): Mice gained weight in all groups post-treatment, with no significant difference between groups. A reduction in lung viral exposure was evident in all treatment groups compared to the vehicle control dosed mice (Figure 1). Coadministration of NTV with MPV displayed a trend towards lower lung viral exposure compared to the vehicle control with ~40-and ~45-fold reduction in AUC for N-and SgE-gene assays, respectively. Dosed individually, NTV and MPV reduced viral exposure 5.7-and 7.7-fold for the N-gene assay, respectively. Differences in total serum IgG concentrations were evident between vehicle and NTV-(34-fold reduction, P=0.018), and MPV-(4.2-fold reduction, P=0.053) treated hamsters. Conclusion(s): These data show virological efficacy of NTV and MPV against the SARS-CoV-2 BA.1 Omicron variant. The combination of NTV and MPV demonstrated a lower viral RNA exposure in the lung than either drug alone, albeit not statistically significant. Initial data indicate potential immune alterations in NTV and MPV dosed hamsters. Studies to clarify the utility of NTV/ MPV combinations and further characterize the impact of antiviral therapy on IgG are warranted.

NAFAMOSTAT AS NASAL CHEMOPROPHYLAXIS FOR SARS-CoV-2 IN HAMSTERS

Background: Chemoprophylaxis is a critical tool for many infectious diseases, and in COVID-19 may have particular benefit for vulnerable patients that do not maximally benefit from vaccination. Nafamostat inhibits TMPRSS2, which catalyses a critical cell entry pathway for SARS-CoV-2. This study sought to assess efficacy of intranasal nafamostat against airborne transmission of SARSCoV-2 in Syrian Golden hamsters. Method(s): Male hamsters were intranasally administered water or 5 mg/kg nafamostat in water twice daily for 5 days (sentinels). One day after treatment initiation, sentinels were co-housed with an untreated hamster that was intranasally inoculated with 1 x 104 PFU of Wuhan SARS-CoV-2 (donor). Sentinels were separated from the donor by a perforated divider, allowing airflow between zones but not contact. Hamsters were weighed and throat-swabbed throughout. At day 4, all animals were culled, and lung and nasal turbinates were harvested. N-RNA was quantified relative to 18S-RNA by qPCR. A 2-way ANOVA with Bonferroni correction was applied to compare weight changes in the nafamostat group to those in controls. An unpaired t-test was used to compare viral RNA in lung and nasal turbinate between groups. Result(s): SARS-CoV-2 viral RNA was significantly lower in the nasal turbinates of nafamostat-treated hamsters compared to water-treated controls (P = 0.012;Figure 1). Within the lung, SARS-CoV-2 RNA was undetectable in the nafamostat-treated hamsters, but was detectable in the water-treated controls. Viral RNA was undetectable in the swabs of the nafamostat-treated hamsters at all timepoints, but was quantifiable in the water-treated control group from day 3. Body weight of the nafamostat-treated hamsters was significantly lower (P = < 0.001) than in the water-treated animals throughout. SARS-CoV-2 viral RNA was detectable in the donor hamsters lung, nasal turbinate and swab samples confirming validity of the experiment. Conclusion(s): This study demonstrated a protective effect of intranasal nafamostat against airborne SARS-CoV-2 transmission in Syrian golden hamsters. A phase IIa study of intravenously administered nafamostat yielded no evidence of clinical efficacy in hospitalised patients, but further investigation of intranasally administered nafamostat in a prophylactic setting may be warranted.

Characterization of the Immune Reaction to Covid-19 Treatment with Dexamethasone: A Narrative Review

Purpose of Study: The spread of SARS-CoV-2 and the resulting Coronavirus Disease 2019 (COVID-19) continues to manifest in individuals in varying severity with limited treatment options available. Despite research efforts put forth in developing therapeutic options for treatment of COVID-19 disease, effective and well understood mechanisms remain limited. Corticosteroid treatment with dexamethasone was shown to be beneficial for those with severe illness early in the pandemic with little understanding of its beneficial mechanism. This narrative review describes the current findings regarding the mechanism of action of dexamethasone treatment in the setting of SARS-CoV-2 infection. Methods Used: A comprehensive search of Embase and PubMed was conducted in consultation with a health sciences librarian. Search terms included (1) COVID-19 (2) dexamethasone (3) animal model and (4) immune response. No limits were used on the search and other reviews were excluded. Search results were screened based on titles and s before being selected for full text review. Outcomes recorded included characterization of the microenvironment of lung tissue following SARS-CoV-2 through cytokine measurement, histopathological staining and analysis of lung tissue, and clinical outcomes such as survival time. Summary of Results: The search resulted in 100 articles. Of these, 8 articles were identified that met the inclusion criteria. Three conducted experiments with Syrian hamsters, two with mice, two with alveolar macrophages, and one study was conducted with human subjects. Dexamethasone treatment was found to diminish inflammatory cytokine levels and preserve the integrity of lung tissue in several animal models and in vitro experiments in the setting of SARS-CoV-2 infection. Dexamethasone treatment was also found to reduce inflammatory cell infiltration of lung tissue infected with SARS-CoV-2. In humans, combination therapy of low dose dexamethasone with spironolactone proved more effective at lowering inflammatory markers than high dose dexamethasone alone. Conclusion(s): Collectively, the articles included in this review support the use of dexamethasone treatment in SARS-CoV-2 infection. Protective effects exhibited with dexamethasone treatment suggest that its action may be linked to the inflammatory nature of COVID-19 disease. Macrophage regulation and diminished inflammatory cytokine levels were hypothesized as possible mechanistic features of dexamethasone action but lacked exact characterization. Further exploration of combination treatment with dexamethasone and its mechanism of action is needed to identify specific and effective therapeutic strategies in the future.

Omicron BA.1 and BA.2 sub-lineages show reduced pathogenicity and transmission potential than the early SARS-CoV-2 D614G variant in Syrian hamsters.

BACKGROUND: The epidemiological advantage of Omicron variant is evidenced by its rapid spread and the ability to outcompete prior variants. Among Omicron sub-lineages, early outbreaks were dominated by BA.1 while BA.2 has gained dominance since February 2022. The relative pathogenicity and transmissibility of BA.1 and BA.2 have not been fully defined. METHODS: We compared viral loads and clinical signs in Syrian hamsters after infection with BA.1, BA.2, or D614G variant. A competitive transmission model and next generation sequencing were used to compare the relative transmission potential of BA.1 and BA.2. RESULTS: BA.1 and BA.2 caused no apparent clinical signs while D614G caused more than 10% weight loss. Higher viral loads were detected from the nasal washes, nasal turbinate and lungs of BA.1 than BA.2 inoculated hamsters. No aerosol transmission was observed for BA.1 or BA.2 under the experimental condition that D614G transmitted efficiently. BA.1 and BA.2 were able to transmit among hamsters via direct contact; however, BA.1 transmitted more efficiently than BA.2 under the competitive transmission model. No recombination was detected from direct contacts exposed simultaneously to BA.1 and BA.2. CONCLUSIONS: Omicron BA.1 and BA.2 demonstrated attenuated pathogenicity and reduced transmission potential in hamsters when compared to early SARS-CoV-2 strains.

A Crisis Within a Crisis: Working and Living Conditions of Syrian and Palestinian Refugees during the COVID-19 in Jordan

The COVID-19 pandemic has evolved into one of the most impactful crises of modern time, and most countries have implemented preventive measures such as nationwide lockdowns, closing certain businesses, and quarantine to prevent the spread of the virus. This study explores how the COVID-19 crisis and its preventive measures impact refugees' welfare in the context of a developing country. The research is based on forty semi-structured interviews with Syrian and Palestinian refugees in Jordan. Research findings indicate that refugees are primarily employed in low-skilled jobs because of legal restrictions, which do not provide decent working conditions and socioeconomic security. Refugees are also mostly housed in high-density settlements with limited access to healthcare, sanitation, hygiene, and water (WASH) facilities. The research findings show that refugees are particularly at risk during the global health crisis due to precarious working and living conditions. This study concludes by providing recommendations on how to respond to future pandemic crises within refugee contexts based on lessons learned from the COVID-19 pandemic. © 2023 Transnational Press London Ltd. All rights reserved.

Efficacy of Plant-Made Human Recombinant ACE2 against COVID-19 in a Golden Syrian Hamster Model.

Coronavirus disease 2019 (COVID-19) is a novel infectious respiratory disease caused by SARS-CoV-2. We evaluated the efficacy of a plant-based human recombinant angiotensin-converting enzyme 2 (hrACE2) and hrACE2-foldon (hrACE2-Fd) protein against COVID-19. In addition, we analyzed the antiviral activity of hrACE2 and hrACE2-Fd against SARS-CoV-2 using real-time reverse-transcription PCR and plaque assays. The therapeutic efficacy was detected using the Golden Syrian hamster model infected with SARS-CoV-2. Both hrACE2 and hrACE2-Fd inhibited SARS-CoV-2 by 50% at concentrations below the maximum plasma concentration, with EC50 of 5.8 µg/mL and 6.2 µg/mL, respectively. The hrACE2 and hrACE2-Fd injection groups showed a tendency for decreased viral titers in nasal turbinate tissues on day 3 after virus inoculation; however, this decrease was not detectable in lung tissues. Histopathological examination on day 9 after virus inoculation showed continued inflammation in the SARS-CoV-2 infection group, whereas decreased inflammation was observed in both the hrACE2 and hrACE2-Fd injection groups. No significant changes were observed at other time points. In conclusion, the potential therapeutic efficacy of plant-based proteins, hrACE2 and hrACE2-Fd, against COVID-19 was confirmed in a SARS-CoV-2-inoculated Golden Syrian hamster model. Further preclinical studies on primates and humans are necessary to obtain additional evidence and determine the effectiveness of these therapies.

SARS-CoV-2 Variant Pathogenesis Following Primary Infection and Reinfection in Syrian Hamsters.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has evolved into multiple variants. Animal models are important to understand variant pathogenesis, particularly for variants with mutations that have significant phenotypic or epidemiological effects. Here, cohorts of naive or previously infected Syrian hamsters (Mesocricetus auratus) were infected with variants to investigate viral pathogenesis and disease protection. Naive hamsters infected with SARS-CoV-2 variants had consistent clinical outcomes, tissue viral titers, and pathology, while hamsters that recovered from initial infection and were reinfected demonstrated less severe clinical disease and lung pathology than their naive counterparts. Males had more frequent clinical signs than females in most variant groups, but few sex variations in tissue viral titers and lung pathology were observed. These findings support the use of Syrian hamsters as a SARS-CoV-2 model and highlight the importance of considering sex differences when using this species. IMPORTANCE With the continued circulation and emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, understanding differences in the effects between the initial infection and a subsequent reinfection on disease pathogenesis is critical and highly relevant. This study characterizes Syrian hamsters as an animal model to study reinfection with SARS-CoV-2. Previous infection reduced the disease severity of reinfection with different SARS-CoV-2 variants.

A Text Mining Approach to Determinants of Attitude Towards Syrian Immigration in the Turkish Twittersphere

This study uses novel deep learning-based language models to extract meaningful information from vast chunks of textual data from Twitter on the competing narratives of the recent Syrian immigration to Turkey. Our analysis identifies five main topics in the framing of Syrian immigration in Turkish Twittersphere. In this paper, we demonstrate correlational links between the timing of landmark events and change in the percent share of trends in those topics across time. We highlight two important observations: (a) Social benefit demands of natives on Twitter rose sharply with the COVID-19 pandemic, leading to ever more widespread sentiments of welfare chauvinism and (b) Patriotic feelings and the implementation of an interventionist foreign policy agenda in the immigrants' country of origin created a relatively tolerant yet patronizing attitude towards migrants. As the COVID-19 pandemic and immigration frequently occupy the center stage in politics of immigrant-hosting societies, our research has international appeal beyond its specific geographical context. [ FROM AUTHOR] Copyright of Social Science Computer Review is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

EXPERIMENTAL MODEL OF SARS COV-2 IN YOUNG SYRIAN HAMSTERS FOR PRECLINICAL STUDIES

SARS-CoV-2 researchers faced the problem of specificity for ACE-2 receptors. In mice and rats, ACE-2 has a low affinity for this virus. In contrast, the Syrian hamster (Mesocricetus auratus) when infected with SARS-CoV-2 show clinical signs of infection with this virus. Therefore, it is necessary to assess the severity of pathological lesions and immune response for relevance to preclinical new drugs against SARS-CoV-2. In this study, we studied blood counts, serum levels of Il-6, TNF-α, IFN-α and IFN-γ and the histological state of the lungs of Syrian hamsters. In our study Syrian hamsters showed clinical signs of COVID-19. In infected animals, a decrease in the level of leukocytes and granulocytes was noted. There was some suppression of the immune response, without an increase in the main biomarkers of ARDS. The exception was high levels of TNF-α. Histological examination showed an early exudative phase of moderate ARDS. There were no significant gender differences in the production of pro-inflammatory cytokines. In this study, it was shown that infection with COVID-19 in young Syrian hamsters is modeled with moderate severity, and can be applied in preclinical studies. © 2022 International Multidisciplinary Scientific Geoconference. All rights reserved.