Antiviral Nanobiologic Therapy Remodulates Innate Immune Responses to Highly Pathogenic Coronavirus.

Highly pathogenic coronavirus (CoV) infection induces a defective innate antiviral immune response coupled with the dysregulated release of proinflammatory cytokines and finally results in acute respiratory distress syndrome (ARDS). A timely and appropriate triggering of innate antiviral response is crucial to inhibit viral replication and prevent ARDS. However, current medical countermeasures can rarely meet this urgent demand. Here, an antiviral nanobiologic named CoVR-MV is developed, which is polymerized of CoVs receptors based on a biomimetic membrane vesicle system. The designed CoVR-MV interferes with the viral infection by absorbing the viruses with maximized viral spike target interface, and mediates the clearance of the virus through its inherent interaction with macrophages. Furthermore, CoVR-MV coupled with the virus promotes a swift production and signaling of endogenous type I interferon via deregulating 7-dehydrocholesterol reductase (DHCR7) inhibition of interferon regulatory factor 3 (IRF3) activation in macrophages. These sequential processes re-modulate the innate immune responses to the virus, trigger spontaneous innate antiviral defenses, and rescue infected Syrian hamsters from ARDS caused by SARS-CoV-2 and all tested variants.

Cross-protective humoral immunity to coronaviruses from SARS coronavirus 2-naïve sera of children with Kawasaki disease.

OBJECTIVES: SARS coronavirus 2 (SARS-CoV-2)-associated multi-system inflammatory syndrome in children indicates that viruses can trigger a Kawasaki disease (KD)-like hyperinflammation. A plausible hypothesis was that coronavirus-specific 'holes' in humoral immunity could cause both diseases. METHODS: To determine whether SARS-CoV-2-naïve patients with KD have inferior humoral immunity for the novel coronavirus, sera of children with KD and control children from year 2015 to 2021 were subjected to ELISA, microwestern, and neutralization assays to evaluate the capabilities in recognizing the receptor-binding domain of SARS-CoV-2, spotting spike proteins of three respiratory syndromic coronaviruses, and blocking SARS-CoV-2 from binding to angiotensin-converting enzyme 2 receptors in vitro, respectively. RESULTS: 29 patients with KD before 2019, 74 patients with KD in 2019 or 2020, 54 non-febrile controls, and 24 febrile controls were included in the study. SARS-CoV-2 was recognized on ELISA for both patients with KD in 2016 and those with KD in 2020. Microwestern demonstrated cross-reactive IgG in an all-or-none manner towards three spike proteins of syndromic coronaviruses regardless of sample year or KD status. The ratio between the sera that recognized all spike proteins and those that recognized none (51 vs. 47) was significantly higher from patients with KD than from non-febrile controls (17 vs. 32; p 0.047) but not from febrile controls (13 vs. 11; p 0.85). Most positive sera (12 of 17 controls, 5 of 8 patients with KD before 2019, and 28 of 33 patients with KD in 2019 or 2020) offered protection comparable to low-titre sera from the WHO reference panel. DISCUSSION: Humoral immunity of SARS-CoV-2-naïve children with KD was not inferior to that of controls in offering cross-protection against the novel coronavirus.

Do personal values and motivation affect women's solo travel intentions in Taiwan?

Female solo travel is experiencing a global increase and specifically, gaining popularity in Asia. This study explores how personal values and female solo travel motivation affect travel behavior. Using a sample comprising 381 single females in Taiwan, partial least squares structural equation modeling was utilized to investigate the hypotheses. The results revealed Hypothesis 1 and Hypothesis 3 are supported, which verifies personal internal values significantly affect female solo travel motivation, and are identified as significant factors influencing female solo travel intention. Additionally, Hypothesis 5 is partially support, indicating the female solo travel motivations of escape/relaxation, relationship, and self-actualization contribute to the formation of positive female solo travel intention. As Hypothesis 2 and Hypothesis 4 are unsupported, external values have no impact on female solo travel motivation or any significant effect on female solo travel intention. This research adds to the vast gap in tourism literature by identifying the personal values and motivations of female solo travel, and benefits the development of the female solo travel market.

A Heterologous Challenge Rescues the Attenuated Immunogenicity of SARS-CoV-2 Omicron BA.1 Variant in Syrian Hamster Model.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is becoming a dominant circulator and has several mutations in the spike glycoprotein, which may cause shifts of immunogenicity, so as to result in immune escape and breakthrough infection among the already infected or vaccinated populations. It is unclear whether infection with Omicron could generate adequate cross-variant protection. To investigate this possibility, we used Syrian hamsters as an animal model for infection of SARS-CoV-2. The serum from Omicron BA.1 variant-infected hamsters showed a significantly lower neutralization effect against infection of the same or different SARS-CoV-2 variants than the serum from Beta variant-infected hamsters. Furthermore, the serum from Omicron BA.1 variant-infected hamsters were insufficient to protect against rechallenge of SARS-CoV-2 Prototype, Beta and Delta variants and itself. Importantly, we found that rechallenge with different SARS-CoV-2 lineages elevated cross-variant serum neutralization titers. Overall, our findings indicate a weakened immunogenicity feature of Omicron BA.1 variant that can be overcome by rechallenge of a different SARS-CoV-2 lineages. Our results may lead to a new guideline in generation and use of the vaccinations to combat the pandemic of SARS-CoV-2 Omicron variant and possible new variants. IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant causes breakthrough infections among convalescent patients and vaccinated populations. However, Omicron does not generate robust cross-protective responses. Here, we investigate whether heterologous SARS-CoV-2 challenge is able to enhance antibody response in a sensitive animal model, namely, Syrian hamster. Of note, a heterologous challenge of Beta and Omicron BA.1 variant significantly broadens the breadth of SARS-CoV-2 neutralizing responses against the prototype, Beta, Delta, and Omicron BA.1 variants. Our findings confirm that vaccination strategy with heterologous antigens might be a good option to protect against the evolving SARS-CoV-2.

Anticipating Z-generation tourists' green hotel visit intention utilizing an extended theory of planned behavior.

Due to the effect COVID-19 epidemic, promoting green consumption is now a key marketing strategy in the hospitality and tourism industry. As it is vital green hotels predict their customers' visit intention, this study attempts to discover the factors affecting Taiwan's Z-generation tourists' green hotel visit intention using an extended theory of planned behavior [including personal moral norms (PMN) and environmental concern (EC)]. Data were gathered from 296 Z-generation tourists via an online survey, which was subsequently analyzed using partial least squares structural equation modeling. The results evidence that Z-generation tourists' attitude, subjective norms, (SN) and perceived behavioral control positively and significantly influence their green hotel visit intention, with attitude being the most significant factor. Moreover, the mediation model analysis indicates Z-generation tourists' attitude toward green hotels mediates the relationships between PMN, SN, EC, and visit intention. This study provides new insights into tourists' green hotel visit intention and emphasizes the importance of attitude in the formation of intention.

Nasal irrigation efficiently attenuates SARS-CoV-2 Omicron infection, transmission and lung injury in the Syrian hamster model.

Recently, a new variant lineage of SARS-CoV-2, namely Omicron, became the dominant global circulating strain. The multiple antigenic mutations of Omicron largely decrease the efficiency of current vaccines and neutralizing antibodies, which highlights the need for more potent and reachable medical countermeasures. Here, we hypothesize that direct viral clearance by nasal irrigation might be a convenient and alternative option, and perform proof-of-concept experiments in the Syrian hamster model. Interestingly, Omicron shows a different dynamic in the changes of viral RNA, viral titers, and proinflammatory cytokines in nasal rinsing samples when compared with the prototype. Meanwhile, the levels of viral load and proinflammatory cytokines in nasal rinsing samples can indicate the severity of lung injury. Of note, daily nasal irrigation efficiently attenuates inflammation and lung injury in Omicron-infected hamsters by decreasing the viral loads in the respiratory tract organs. Moreover, daily nasal irrigation effectively suppresses viral transmission by close contact.

Infection, pathology and interferon treatment of the SARS-CoV-2 Omicron BA.1 variant in juvenile, adult and aged Syrian hamsters.

The new predominant circulating SARS-CoV-2 variant, Omicron, can robustly escape current vaccines and neutralizing antibodies. Although Omicron has been reported to have milder replication and disease manifestations than some earlier variants, its pathogenicity in different age groups has not been well elucidated. Here, we report that the SARS-CoV-2 Omicron BA.1 sublineage causes elevated infection and lung pathogenesis in juvenile and aged hamsters, with more body weight loss, respiratory tract viral burden, and lung injury in these hamsters than in adult hamsters. Juvenile hamsters show a reduced interferon response against Omicron BA.1 infection, whereas aged hamsters show excessive proinflammatory cytokine expression, delayed viral clearance, and aggravated lung injury. Early inhaled IFN-α2b treatment suppresses Omicron BA.1 infection and lung pathogenesis in juvenile and adult hamsters. Overall, the data suggest that the diverse patterns of the innate immune response affect the disease outcomes of Omicron BA.1 infection in different age groups.

Estimating daily ground-level NO2 concentrations over China based on TROPOMI observations and machine learning approach

Nitrogen dioxide (NO2) is an important target for monitoring atmospheric quality. Deriving ground-level NO2 concentrations with much finer resolution, it requires high-resolution satellite tropospheric NO2 column as input and a reliable estimation algorithm. This paper aims to estimate the daily ground-level NO2 concentrations over China based on machine learning models and the TROPOMI NO2 data with high spatial resolution. In this study, four tree-based algorithm machine learning models, decision trees (DT), gradient boost decision tree (GBDT), random forest (RF) and extra-trees (ET), were used to estimate ground-level NO2 concentrations. In addition to considering many influencing factors of the ground-level NO2 concentrations, we especially introduced simplified temporal and spatial information into the estimation models. The results show that the extra-trees with spatial and temporal information (ST-ET) model has great performance in estimating ground-level NO2 concentrations with a cross-validation R2 of 0.81 and RMSE of 3.45 μg/m3 in test datasets. The estimated results for 2019 based on the ST-ET model achieves a satisfactory accuracy with a cross-validation R2 of 0.86 compared with the other models. Through time-space analysis and comparison, it was found that the estimated high-resolution results were consistent with the ground observed NO2 concentrations. Using data from January 2020 to test the prediction power of the models, the results indicate that the ST-ET model has a good performance in predicting ground-level NO2 concentrations. Taking four ground-level NO2 concentrations hotspots as examples, the estimated ground-level NO2 concentrations and ground-based observation data during the coronavirus disease (COVID-19) pandemic were lower compared with the same period in 2019. The findings offer a solid solution for accurately and efficiently estimating ground-level NO2 concentrations by using satellite observations, and provide useful information for improving our understanding of the regional atmospheric environment.

The Role of Vitamin D in SARS-CoV-2 Infection and Acute Kidney Injury.

Vitamin D has been described as an essential nutrient and hormone, which can cause nuclear, non-genomic, and mitochondrial effects. Vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences the cell metabolism and maintenance specific nuclear programs. Given its broad spectrum of activity and multiple molecular targets, a deficiency of vitamin D can be involved in many pathologies. Vitamin D deficiency also influences mortality and multiple outcomes in chronic kidney disease (CKD). Active and native vitamin D serum levels are also decreased in critically ill patients and are associated with acute kidney injury (AKI) and in-hospital mortality. In addition to regulating calcium and phosphate homeostasis, vitamin D-related mechanisms regulate adaptive and innate immunity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have a role in excessive proinflammatory cell recruitment and cytokine release, which contribute to alveolar and full-body endothelial damage. AKI is one of the most common extrapulmonary manifestations of severe coronavirus disease 2019 (COVID-19). There are also some correlations between the vitamin D level and COVID-19 severity via several pathways. Proper vitamin D supplementation may be an attractive therapeutic strategy for AKI and has the benefits of low cost and low risk of toxicity and side effects.

COVID-19 Shock, Financial Flexibility, and Hotels' Performance Nexus.

This study investigates the nexus of coronavirus disease 2019 (COVID-19) shock, financial flexibility (FF), and firm performance (FP) in Taiwan listed hotel firms. Quantile regression (QR) methods were used to analyze the data from Taiwan Stock Exchange listed hotel firms between 2020 Q1 and 2021 Q2. The results evidence that there is an inversed U-shaped linkage between FF and FP for the hotel industry. Additionally, FF has an inverted U-shaped effect on FP for the asset-light hotel firms for all quantiles except the 50th quantile. In addition, FF also has an inverted U-shaped impact on FP for the asset-heavy hotel firms in the 10th and 90th quantiles. A significant finding in this study is that there is a concave non-linear relationship between FF and FP, consistent with the law of diminishing marginal return. That is, with an increase in FF, the FP is on the rise; when FF exceeds the inflection point level, the FP begins to decline. Thus, a firm must ensure that the FF strategy it adopts must be the most efficient and effective, i.e., it must bring the trade-off between costs and benefits. The empirical results highlight the need for the hotel industry of Taiwan to take the rolling adjustment and optimization of FF after the COVID-19 pandemic for long-term sustainability.

The role of anti-platelet factor 4 antibodies and platelet activation tests in patients with vaccine-induced immune thrombotic thrombocytopenia: Brief report on a comparison of the laboratory diagnosis and literature review.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human pathogen causing coronavirus disease 2019 (COVID-19). Rare cases of COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) after the ChAdOx1 nCoV-19 (AstraZeneca) vaccination have been reported. We performed a test for anti-heparin/ platelet factor 4 (PF4) antibodies and functional assay using flow cytometry. METHOD: A healthy woman presented to the emergency department with chest pain, headache, and abdominal pain after the first vaccination with AstraZeneca. Polymerase chain reaction (PCR) test for SARS-CoV-2 was negative. Chest computed tomography (CT) showed pulmonary artery embolism and brain magnetic resonance imaging (MRI) revealed cerebral sinus-venous thrombosis. Abdominal CT demonstrated the thrombosis with occlusion in her right hepatic vein. Laboratory studies revealed decreased platelet counts, and high D-dimer level. Finally, laboratory results indicated high PF4 antibodies level high and a positive platelet activation test, confirming the diagnosis of VITT. RESULTS: Treatments including intravenous immunoglobulin, methylprednisolone and direct oral anticoagulant were administered. The results of a follow-up platelet count and D-dimer were normal. In addition, the titer of PF4 antibodies (optical density: 0.425; normal ≤ 0.4, enzyme-linked immunosorbent assay) fell. After a 3-month follow-up, her general condition improved gradually. CONCLUSIONS: The use of COVID-19 vaccines to prevent SARS-CoV-2 infections and complications is considered the most practicable policy for controlling the COVID-19 pandemic and is being forcefully pursued in the global area. Appropriate laboratory diagnosis facilitates the accurate and rapid diagnosis. Early recognizing and appropriate strategies for VITT are required and can provide these patients with more favorable patient outcomes. This report also elected to make comparisons of clinical manifestation, laboratory diagnosis, and management in patients with VITT.

Assessing the Knowledge, Attitudes and Practices of COVID-19 among Quarantine Hotel Workers in China.

During the pandemic, quarantine hotel workers face a higher risk of infection while they host quarantine guests from overseas. This study's aim is to gain an understanding of the knowledge, attitudes, and practices (KAP) of quarantine hotel workers in China. A total of 170 participants took part in a cross-sectional survey to assess the KAP of quarantine hotel workers in China, during the COVID-19 pandemic. The chi-square test, independent t-test, one-way analysis of variance (ANOVA), descriptive analysis, and binary logistic regression were used to examine the sociodemographic factors associated with KAP levels during the COVID-19 pandemic. The results show that 62.41% have good knowledge, 94.7% have a positive attitude towards COVID-19, but only 78.2% have good practices. Most quarantine hotel workers (95.3%) are confident that COVID-19 will be successfully controlled and that China is handling the COVID-19 crisis well (98.8%). Most quarantine hotel workers are also taking personal precautions, such as avoiding crowds (80.6%) and wearing facemasks (97.6%). The results evidence that quarantine hotel workers in China have acquired the necessary knowledge, positive attitudes and proactive practices in response to the COVID-19 pandemic. The results of this study can provide a reference for quarantine hotel workers and their targeted education and intervention.

The Association Between Fear of Coronavirus Disease 2019, Mental Health, and Turnover Intention Among Quarantine Hotel Employees in China.

During the coronavirus disease 2019 (COVID-19) pandemic, quarantine hotel employees face a higher risk of infection while they host quarantine guests from overseas. This is the first research to empirically investigate the psychological effects of operating a quarantine hotel on its employees. The empirical results indicate that heightened fear of COVID-19 leads to adverse mental health issues for quarantine hotel employees and confirm that depression, anxiety, and stress have a significant influence on turnover intention. These findings contribute to the extant knowledge base by uncovering the role of mental health in employee turnover intention. Based on the results, implications are presented for practitioners.

A SCID mouse-human lung xenograft model of SARS-CoV-2 infection.

SARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause life-threatening pneumonia, respiratory failure and even death. Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics. However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for in vitro/in vivo models to investigate authentic SARS-CoV-2 infection in primary human lung cells or tissues with mature structures. The present study was designed to evaluate a humanized mouse model carrying human lung xenografts for SARS-CoV-2 infection in vivo. Methods: Human fetal lung tissue surgically grafted under the dorsal skin of SCID mice were assessed for growth and development after 8 weeks. Following SARS-CoV-2 inoculation into the differentiated lung xenografts, viral replication, cell-type tropism and histopathology of SARS-CoV-2 infection, and local cytokine/chemokine expression were determined over a 6-day period. The effect of IFN-α treatment against SARS-CoV-2 infection was tested in the lung xenografts. Results: Human lung xenografts expanded and developed mature structures closely resembling normal human lung. SARS-CoV-2 replicated and spread efficiently in the lung xenografts with the epithelial cells as the main target, caused severe lung damage, and induced a robust pro-inflammatory response. IFN-α treatment effectively inhibited SARS-CoV-2 replication in the lung xenografts. Conclusions: These data support the human lung xenograft mouse model as a useful and biological relevant tool that should facilitate studies on the pathogenesis of SARS-CoV-2 lung infection and the evaluation of potential antiviral therapies.

Gender associates with both susceptibility to infection and pathogenesis of SARS-CoV-2 in Syrian hamster.

Epidemiological studies of the COVID-19 patients have suggested the male bias in outcomes of lung illness. To experimentally demonstrate the epidemiological results, we performed animal studies to infect male and female Syrian hamsters with SARS-CoV-2. Remarkably, high viral titer in nasal washings was detectable in male hamsters who presented symptoms of weight loss, weakness, piloerection, hunched back and abdominal respiration, as well as severe pneumonia, pulmonary edema, consolidation, and fibrosis. In contrast with the males, the female hamsters showed much lower shedding viral titers, moderate symptoms, and relatively mild lung pathogenesis. The obvious differences in the susceptibility to SARS-CoV-2 and severity of lung pathogenesis between male and female hamsters provided experimental evidence that SARS-CoV-2 infection and the severity of COVID-19 are associated with gender.