SARS-CoV-2 NSP13 interacts with host IRF3, blocking antiviral immune responses.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses an unprecedented threat to human health since late 2019. Notably, the progression of the disease is associated with impaired antiviral interferon (IFN) responses. Although multiple viral proteins were identified as potential IFN antagonists, the underlying molecular mechanisms remain to be fully elucidated. In this study, we firstly demonstrate that SARS-CoV-2 NSP13 protein robustly antagonizes IFN response induced by the constitutively active form of transcription factor IRF3 (IRF3/5D). This induction of IFN response by IRF3/5D is independent of the upstream kinase, TBK1, a previously reported NSP13 target, thus indicating that NSP13 can act at the level of IRF3 to antagonize IFN production. Consistently, NSP13 exhibits a specific, TBK1-independent interaction with IRF3, which, moreover, is much stronger than that of NSP13 with TBK1. Furthermore, the NSP13-IRF3 interaction was shown to occur between the NSP13 1B domain and IRF3 IRF association domain (IAD). In agreement with the strong targeting of IRF3 by NSP13, we then found that NSP13 blocks IRF3-directed signal transduction and antiviral gene expression, counteracting IRF3-driven anti-SARS-CoV-2 activity. These data suggest that IRF3 is likely to be a major target of NSP13 in antagonizing antiviral IFN responses and provide new insights into the SARS-CoV-2-host interactions that lead to viral immune evasion.

Cost-effectiveness analysis of COVID-19 screening strategy under China's dynamic zero-case policy.

This study aims to optimize the COVID-19 screening strategies under China's dynamic zero-case policy through cost-effectiveness analysis. A total of 9 screening strategies with different screening frequencies and combinations of detection methods were designed. A stochastic agent-based model was used to simulate the progress of the COVID-19 outbreak in scenario I (close contacts were promptly quarantined) and scenario II (close contacts were not promptly quarantined). The primary outcomes included the number of infections, number of close contacts, number of deaths, the duration of the epidemic, and duration of movement restriction. Net monetary benefit (NMB) and the incremental cost-benefit ratio were used to compare the cost-effectiveness of different screening strategies. The results indicated that under China's COVID-19 dynamic zero-case policy, high-frequency screening can help contain the spread of the epidemic, reduce the size and burden of the epidemic, and is cost-effective. Mass antigen testing is not cost-effective compared with mass nucleic acid testing in the same screening frequency. It would be more cost-effective to use AT as a supplemental screening tool when NAT capacity is insufficient or when outbreaks are spreading very rapidly.

Reliability and validity evaluation of the chinese revision of the attitude towards adult vaccination scale.

BACKGROUND: Although vaccination is one of the critical interventions to address global health issues, inadequate vaccination rates has become an international challenge. Vaccine hesitancy is the key to affecting inadequate vaccination rates. According to the WHO SAGE working group's definition, vaccine hesitancy refers to delaying or refusing vaccination and has been ranked as one of the top 10 health threats. There has yet to be a scale that evaluates vaccination attitudes among Chinese adults. However, an attitude quantity, the adult vaccination attitude scale, has been developed to assess adult vaccination attitudes and reasons for vaccine hesitancy. OBJECTIVE: The Adult Attitudes to Vaccination Scale (ATAVAC) was initially developed by Professor Zoi Tsimtsiou et al. This study aimed to analyze the structure of the Chinese version of the ATAVAC and explore the relationship between adult vaccination attitudes, e-health literacy, and medical distrust. METHODS: After obtaining author permission for the initial scales, the study was translated using the Brislin back-translation method. 693 adults were enrolled to the study. To validate this hypothesis, participants finished the socio-demographic questionnaire, the Chinese version of the ATAVAC, the electronic Health Literacy Scale (e-HEALS) and the Medical Mistrust Index (MMI). The exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to examine the underlying structure of the factors of the Chinese version of the Adult Vaccination Attitude Scale and to measure its reliability and validity. RESULTS: The Cronbach's alpha coefficient for the Chinese version of the ATAVAC was 0.885, with Cronbach's alpha coefficients ranging from 0.850 to 0.958 for each dimension. The content validity index was 0.90, and the retest reliability was 0.943. The exploratory factor analysis (EFA) supported the 3-factor structure of the translation instrument, and the scale had good discriminant validity. The confirmatory factor analysis (CFA) revealed a degree of freedom of 1.219, a model fit index (GFI) of 0.979, a normative fit index (NFI) of 0.991, a Tucker-Lewis index (TLI) of 0.998, a comparability index (CFI) of 0.998 and a root mean square error of approximation (RMSEA) of 0.026. CONCLUSION: The results show that the Chinese version of the ATAVAC has demonstrated good reliability and validity. Hence, it can be used as an effective tool to assess vaccination attitudes among Chinese adults.

[Main Infection Control Measures for Respiratory Infectious Diseases in Medical Institutions and Public Places in China].

Respiratory infectious diseases (RID) are the major public health problems threatening the people's lives and health.Infection control (IC) is one of the effective tools to contain the occurrence and spread of RID.We collected the articles and data on IC published since January 1,2018 and summarized the achievements,problems,and challenges of IC from administrative control,management control,environment and engineering control,and personal protection in the medical institutions and public places in China.The efforts for IC vary in different regions and medical institutions of different levels.There are still links to be improved for IC from administrative control,management control,environment and engineering control,and personal protection,especially in community-level medical institutions and public areas.It is urgent to strengthen the implementation of IC policies and conduct IC precisely according to local situations.We proposed the following suggestions.First,the existing IC products and tools should be applied to precisely implement the IC measures;second,modern high technology should be employed to develop efficient and convenient IC products and tools;finally,a digital or intelligent IC platform should be built for monitoring infections,so as to contain the occurrence and spread of RID.

Investigation on the Control of COVID-19 in Wuhan: Number of Infections Outside Hospitals and the Reproduction Number.

COVID-19 is erupting globally, and Wuhan successfully controlled it within a month. Infections arose from infectious persons outside hospitals. After data revision, data-based and model-based analyses were implemented, and the conclusions are as follows. The incubation period of most infected people may be 6-7 days. The number of infectious persons outside hospitals in Wuhan on January 20, 2020 was about 10000 and reached more than 20000 on the day of Lockdown; it exceeded 72000 on February 4. Both data-based and model-based analyses gave out the evolution of the reproduction number, which was over 2.5 in early January, went down to 1.62 in late January and 1.20 in early February, with a sudden drop to less than 0.5 due to the strict Stay-at-home management after February 11. Strategies of Stay-at-home, Safe-protective measures, and Ark hospitals were the main contributions to control COVID-19 in Wuhan. In Wuhan, 2 inflection points of COVID-19, exactly correspond to February 5 and February 15, the 2 days when Ark hospitals were introduced, and the complete implementation of Stay-at-home. Based on the expression of the reproduction number, group immunity is also discussed. It shows that only when the group immunization rate is over 75% can COVID-19 be under control; group immunity would be full infection and the total deaths will be 220000 for a city as big as Wuhan. Sensitivity analysis suggests that 30% of people staying at home in combination with better behavior changes, such as social-distancing and frequent handwashing, can effectively contain COVID-19. However, only when this proportion is over 60% can the controlled effect and efficiency like Wuhan be obtained.

Epidemiological and etiological analysis of a case cluster caused by norovirus in a nursing home in Lanzhou

Objective: To understand the epidemiology and etiology of a cluster of cases with gastroenteritis in a nursing home in Anning district of Lanzhou, and to provide a scientific evidence for the prevention and control of norovirus diarrhea in community nursing centers. Methods: From January 28 to February 4 2021, an epidemiological investigation was conducted on all diarrhea cases, nursing staff and chefs in a nursing home in Anning district, Lanzhou city. Samples of patients' anal swabs, feces, vomitus were collected for norovirus detection by real-time fluorescent PCR. ORF1/ORF2 junction region of norovirus in some selected positive samples(Ct value 25) was sequenced. MEGA-X software was used to construct a phylogenetic tree for genetic evolution analysis using the neighboring method. Results: The first case was confirmed on January20,2021, and the number of cases peaked during January 25and 29.A total of 58 clinically diagnosed cases were reported,57were older people, with an incidence of(57/360,15.83%). Diarrhea(50/58,86.21%),vomiting(35/58,60.34%),nausea(13/58,22.41%)and abdominal pain(6/58,10.34%)were common symptoms, all cases were mild. Fifty-three asymptomatic cases were detected among chefs, housekeepers and nurses.A total of 163specimens were tested, the positive rate of norovirus GII was 49.08%(80/163). The positive rate of fecal samples collected from nurses, chefs and housekeepers was 48.62%(53/109), and was11.11%(2/18)in environmental surface swabs. The possibility of other pathogenic infections such as SARS-CoV-2was ruled out by further tests. Thirteen positive samples were selected for sequencing, and 9were successfully sequenced, they were all recombinant GII.4Sydney_2012 [P16]genotypes, forming an independent cluster, while in a large evolutionary branch with the 2020GII.10 [P16]and 2019GII.2 [P16]virus strains in Lanzhou city, showing a relative close genetic connection. Conclusions: GII .4Sydney_2012[P16]genotype of norovirus is found to be causative pathogen of this outbreak, and close contact is the main reason of the outbreak and persistence of the infection,so asymptomatic infections of norovirus play an important role in the disease spreading. Therefore, public health management in nursing homes and other centralized nursing facilities should be strengthened especially for asymptomatic workers in order to prevent virus transmission.

Local Complement Contributes to Pathogenic Activation of Lung Endothelial Cells in SARS-CoV-2 Infection.

Endothelial dysfunction and inflammation contribute to the vascular pathology of Coronavirus Disease 2019 (COVID-19). However, emerging evidence does not support direct infection of endothelial or other vascular wall cells and thus inflammation may be better explained as secondary responses to epithelial cell infection. In this study, we sought to determine whether lung endothelial or other resident vascular cells are susceptible to productive SARS-CoV-2 infection and how local complement activation contributes to endothelial dysfunction and inflammation in response to hypoxia and SARS-CoV-2 infected lung alveolar epithelial cells. We found that ACE2 and TMPRSS2 mRNA expression in lung vascular cells including primary human lung microvascular endothelial cells (HLMVEC), pericytes, smooth muscle cells and fibroblasts was 20-90-fold lower compared to primary human alveolar epithelial type II (AT2) cells. Consistently, we found that HLMVEC and other resident vascular cells were not susceptible to productive SARS-CoV-2 infection under either normoxic or hypoxic conditions. However, viral uptake without replication (abortive infection) was observed in HLMVEC when exposed to conditioned medium from SARS-CoV-2 infected human ACE2 stably transfected A549 epithelial cells (hACE2-A549). Furthermore, we demonstrated that exposure of HLMVEC to conditioned medium from SARS-CoV-2 infected hACE2-A549 cells and hypoxia resulted in upregulation of inflammatory factors such as ICAM1, VCAM1, IL-6 as well as complement components such as C3, C3AR1, C1QA and CFB. Taken together, our data support a model in which lung endothelial/vascular dysfunction during COVID-19 involves the activation of complement and inflammatory signaling and does not involve productive viral infection of endothelial cells. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

COVID-19 lockdowns promoted recovery of the Yangtze river's aquatic ecosystem

The impacts of COVID-19 lockdowns on human life, air quality, and river water quality around the world have received significant attention. In comparison, assessments of the implications for freshwater ecosystems are relatively rare. This study explored the impact of COVID-19 lockdowns on aquatic ecosystems in the Yangtze River by comparing river water quality, phytoplankton, zooplankton, and fish data collected at the site in the middle reach of the Yangtze River in 2018 and 2020. The results show that during COVID-19 lockdowns, the reduction in industrial and domestic effluent discharge led to a reduction in organic pollution and industrial plant nutrient pollution in rivers. Among them, PO43--P, CODMn, and TP were significantly decreased (p < 0.05). During lockdowns, nutrient supplies such as TN and TP were reduced, which led to inhibition of algae growth and decreased phytoplankton abundance. Phytoplankton affects the abundance of zooplankton through a bottom-up effect, and a decrease in phytoplankton density leads to a decrease in zooplankton density. The decrease in plankton density led to lower primary productivity in rivers, reduced fish feed supplies, intensified competition among fish populations, with increases in population dominated by high trophic level carnivorous fish. In addition, the decrease in fishing intensity has contributed to an increase in the number of rivers-sea migratory fish;the fish community was earlier mainly dominated by small-sized species with a short life cycle, and the number of supplementary populations has now increased. As a consequence, the fish community structure shows a tendency toward high complexity and high fish diversity. Overall, these observations demonstrate that the rapid revival of the retrogressive Yangtze River ecosystem is possible through limitation of anthropic interferences.

Qi defensivum (Wehrenergie, weiqi): Moderne Anwendung auf Basis der „Abhandlung über schädigende Kälte (algor laedens)" (Shanghan lun) und der Lehre von morbi temperati (Wärme-Erkrankungen, wenbing) Defensive qi (qi defensivum, weiqi): its modern use according to the treatise on cold damage (Shanghan lun) and the doctrine of warm diseases (morbi temperati, wenbing)

Das qi defensivum (Wehrenergie, weiqi) verbreitet sich in der extima (Oberfläche, biao) und fließt durch die Leitbahnen. Das qi defensivum (Wehrenergie, weiqi) schützt den Körper vor äußeren Heteropathien (Schrägläufigkeiten, xie). Darüber hinaus reguliert das qi defensivum (Wehrenergie, weiqi) vegetative Funktionen wie die Körpertemperatur, das Schwitzen, den zirkadianen Rhythmus und die Wahrnehmungen. Im System der sechs Leitbahnen in der „Abhandlung über schädigende Kälte (algor laedens)" (Shanghan lun) wird eine Störung des yang maior (Großes Yang, taiyang) als eine Erkrankung des qi defensivum (Wehrenergie, weiqi) betrachtet. Im Vier-Schichten-Modell der morbi temperati (Wärme-Erkrankungen, wenbing) bezieht sich eine Störung der Schicht des qi defensivum (Wehrenergie, weiqi) auf das Frühstadium von Fieber aufgrund von calor-Heteropathien („Wärme"-/„Hitze"-Schrägläufigkeiten, rexie), beispielsweise Influenza, Lungenentzündung, Covid-19 etc. Der vorliegende Artikel zitiert Passagen aus der „Abhandlung über schädigende Kälte (algor laedens)" (Shanghan lun) und aus dem System der morbi temperati (Wärme-Erkrankungen, wenbing), nennt zusätzlich die jeweilige Akupunktur- und Moxibustionsbehandlung und wendet die Theorie des qi defensivum (Wehrenergie, weiqi) an, um Long Covid, Schlafstörungen, Depressionen und Angststörungen, Schwitzen und Bi-Syndrom zu behandeln.

Entry, egress and vertical transmission of SARS-CoV-2.

The high infectivity and pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused the COVID-19 outbreak, one of the most devastating pandemics in more than a century. This pandemic has already left a trail of destruction, including enormous loss of life, a global economic slump, and widespread psychological damage. Despite assiduous world-wide endeavors, an effective cure for COVID-19 is still lacking. Surprisingly, infected neonates and children have relatively mild clinical manifestations and a much lower fatality rate than elderly adults. Recent studies have unambiguously demonstrated the vertical transmission of SARS-CoV-2 from infected pregnant women to fetuses, which creates yet another challenge for disease prevention. In this review, we will summarize the molecular mechanism for entry of SARS-CoV-2 into host cells, the basis for the failure of the lungs and other organs in severe acute cases, and the evidence for congenital transmission.

Nursing students' experiences with patient death and palliative and end-of-life care: A systematic review and meta-synthesis.

AIM: To synthesise the experiences of nursing students encountering patient death and caring for patients under palliative care or at end-of-life and their families in clinical settings BACKGROUND: Nurses are pivotal in caring for dying patients and families. It has been reported that nursing students feel unprepared in caring for dying patients and handling patient death. Understanding their experiences would better inform how palliative care education can be improved and how students can be better supported in clinical settings. DESIGN: A qualitative systematic review and meta-synthesis METHODS: PubMed, Embase, CINAHL, PsycINFO, ProQuest and Google Scholar were searched for peer-reviewed articles and theses/dissertations published between 1 January 2012-25 Feb 2023. Qualitative studies of any design reporting nursing students' experiences of patient death, caring for patients under palliative care, at end-of-life, or with time-limiting diseases in clinical settings in English were included. Study quality was evaluated using the Critical Appraisal Skills Programme tool. Data were synthesised using Sandelowski and Barroso's 2-step framework through a meta-summary using thematic analysis, which were then integrated into meta-syntheses using an event timeline. RESULTS: The review included 71 studies from 26 countries (n = 1586 nursing students). The meta-summary contained 8 themes and 23 subthemes: (1) Communication experience with patients and families, (2) Satisfaction with care provided to patients and families, (3) Impact of the COVID-19 pandemic on death and dying, (4) Perceptions of death and dying, (5) Impact of death, (6) Nursing education on palliative end-of-life care, (7) Support systems and coping methods, (8) Learning outcomes. The meta-synthesis depicted nursing students' experiences before, during and after encountering dying patients, families and patient death. Suggestions for nursing faculty and clinical staff on how they could equip students with necessary skills and knowledge and support them in clinical settings were also provided. CONCLUSIONS: While caring for dying patients and families was beneficial to nursing students' learning and professional development, they encountered many challenges. Governments, clinical and academic nursing leaders must prioritise the integration of palliative care content into the curricula across nursing schools in face of increasing palliative and end-of-life care needs in patients. Nursing schools should ensure that students are adequately prepared by designing culturally and socioeconomically relevant curricula, integrating theoretical and experiential learning and offering students a thorough understanding of palliative and end-of-life care. Clinical staff and nursing instructors should support students emotionally and guide them in patient care.

HLA-Bw4 in association with KIR3DL1 favors natural killer cell-mediated protection against severe COVID-19.

Replicating SARS-CoV-2 has been shown to degrade HLA class I on target cells to evade the cytotoxic T-cell (CTL) response. HLA-I downregulation can be sensed by NK cells to unleash killer cell immunoglobulin-like receptor (KIR)-mediated self-inhibition by the cognate HLA-I ligands. Here, we investigated the impact of HLA and KIR genotypes and HLA-KIR combinations on COVID-19 outcome. We found that the peptide affinities of HLA alleles were not correlated with COVID-19 severity. The predicted poor binders for SARS-CoV-2 peptides belong to HLA-B subtypes that encode KIR ligands, including Bw4 and C1 (introduced by B*46:01), which have a small F pocket and cannot accommodate SARS-CoV-2 CTL epitopes. However, HLA-Bw4 weak binders were beneficial for COVID-19 outcome, and individuals lacking the HLA-Bw4 motif were at higher risk for serious illness from COVID-19. The presence of the HLA-Bw4 and KIR3DL1 combination had a 58.8% lower risk of developing severe COVID-19 (OR = 0.412, 95% CI = 0.187-0.904, p = 0.02). This suggests that HLA-Bw4 alleles that impair their ability to load SARS-CoV-2 peptides will become targets for NK-mediated destruction. Thus, we proposed that the synergistic responsiveness of CTLs and NK cells can efficiently control SARS-CoV-2 infection and replication, and NK-cell-mediated anti-SARS-CoV-2 immune responses being mostly involved in severe infection when the level of ORF8 is high enough to degrade HLA-I. The HLA-Bw4/KIR3DL1 genotype may be particularly important for East Asians undergoing COVID-19 who are enriched in HLA-Bw4-inhibitory KIR interactions and carry a high frequency of HLA-Bw4 alleles that bind poorly to coronavirus peptides.

Changes in Patient Perceptions of the Provider Most Involved in Care During COVID-19 and Corresponding Effects on Patient Trust.

During COVID-19 routine clinical operations were disrupted, including limits on the types of providers allowed to perform in-person care and frequency of times they could enter a patient's room. Whether these changes affected patients' trust in the care they received during hospitalization is unknown. Hospitalized patients on the general medicine service were called after discharge and asked to identify who (attending, resident, etc.) was most involved in their inpatient care, and how much trust they had in the physician caring for them. During the pandemic patients were more likely to report attending physicians (29% to 34%) and nurses (30% to 35%), and less likely to report residents/interns (8.1% to 6.5%) or medical students (1.7% to 1.4%) as most involved in their care (chi-squared test, p = 0.04). Patients reporting their attending physician as most involved in their care were more likely to report trusting their doctor (chi-squared test, p < 0.01). As such, trends in medical education that limit trainees' time in direct patient care may affect the development of clinical and interpersonal skills necessary to establish patient trust.

Utilization of telehealth services in low- and middle-income countries amid the COVID-19 pandemic: a narrative summary.

BACKGROUND: During the current period of the pandemic, telehealth has been a boon to the healthcare system by providing quality healthcare services at a safe social distance. However, there has been slow progress in telehealth services in low- and middle-income countries with little to no evidence of the cost and effectiveness of such programmes. OBJECTIVE: To provide an overview of the expansion of telehealth in low- and middle-income countries amid the COVID-19 pandemic and identify the challenges, benefits, and costs associated with implementing telehealth services in these countries. METHODS: We performed a literature review using the search term: '*country name* AND ((telemedicine[Title][Abstract]) OR (telehealth[Title][Abstract] OR eHealth[Title][Abstract] OR mHealth[Title][Abstract]))'. Initially, we started with 467 articles, which were reduced to 140 after filtering out duplicates and including only primary research studies. Next, these articles were screened based on established inclusion criteria and 44 articles were finalised to be used in the review. RESULTS: We found telehealth-specific software being used as the most common tool to provide such services. Nine articles reported patient satisfaction of greater than 90% with telehealth services. Moreover, the articles identified the ability to make a correct diagnosis to resolve the condition, efficient mobilisation of healthcare resources, increased accessibility for patients, increased service utilisation, and increased satisfaction as benefits of telehealth services, whereas inaccessibility, low technological literacy, and lack of support, poor security standards and technological concerns, loss of interest by the patients, and income impacts on physicians as challenges. The review could not find articles that explored the financial information on telehealth programme implementation. CONCLUSION: Although telehealth services are growing in popularity, the research gap on the efficacy of telehealth is high in low- and middle-income countries. To better guide the future development of telehealth services, rigorous economic evaluation of telehealth is needed.

Experience of the homecare of children on automatic peritoneal dialysis during the COVID-19 outbreak: A qualitative descriptive study.

AIMS: To describe the home care experience, challenges and coping strategies of caregivers with children on automatic peritoneal dialysis (PD) in mainland China during the early stage of the COVID-19 outbreak. DESIGN: A qualitative descriptive approach was adopted. Semi-structured telephone interviews were conducted among 14 families with children on automatic peritoneal dialysis from February 2nd to 10th, 2020. The care routine, stress and coping strategies of caregivers of children on peritoneal dialysis were collected. The data were analysed using thematic analysis. METHODS: Four key themes were defined: (1) concerns about PD treatment intertwined with worries about COVID-19; (2) retaining a sense of normality in the middle of the challenges; (3) staying safe; and (4) staying positive and carrying on. RESULTS: Families with children on automatic PD addressed the stress from COVID-19 and its containment measures by closely adhering to COVID-19 preventative measures, actively adjusting mentality and maintaining a sense of normality during the outbreak. This implies that healthcare staff need to be more aware of the complex medical needs of families with children on automatic PD, advocate for them and facilitate their navigation through the repurposed healthcare system.

A transnational lens into international student experiences of the COVID-19 pandemic.

We analyse the experiences of international students living in Canada during the COVID-19 pandemic through the lens of transnationalism that understands mobility as broadly uninterrupted, continuing and taken-for-granted, and international student migration (ISM) literature. With the onset of the COVID-19 pandemic, people had to contend with sudden border closures and stringent restrictions on all forms of travel. International students are regarded as the archetypal trans-migrants with frequent mobility and often multiple attachments to place. We interrogate these assumptions of mobility by drawing on interview data from 13 international students in Ontario from April to June of 2020. We found that international students experienced the pandemic transnationally and faced increased challenges, which heightened their reliance on support from transnational families, and generated anxieties about their future career and mobilities. We bring transnational theories into conversation with ISM literature to better understand international students' lived experiences in Canada during a pandemic.

Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin.

In the last 2 decades, pathogens originating in animals may have triggered three coronavirus pandemics, including the coronavirus disease 2019 pandemic. Thus, evaluation of the spillover risk of animal severe acute respiratory syndrome (SARS)-related coronavirus (SARSr-CoV) is important in the context of future disease preparedness. However, there is no analytical framework to assess the spillover risk of SARSr-CoVs, which cannot be determined by sequence analysis alone. Here, we established an integrity framework to evaluate the spillover risk of an animal SARSr-CoV by testing how viruses break through key human immune barriers, including viral cell tropism, replication dynamics, interferon signaling, inflammation, and adaptive immune barriers, using human ex vivo lung tissues, human airway and nasal organoids, and human lung cells. Using this framework, we showed that the two pre-emergent animal SARSr-CoVs, bat BtCoV-WIV1 and pangolin PCoV-GX, shared similar cell tropism but exhibited less replicative fitness in the human nasal cavity or airway than did SARS-CoV-2. Furthermore, these viruses triggered fewer proinflammatory responses and less cell death, yet showed interferon antagonist activity and the ability to partially escape adaptive immune barriers to SARS-CoV-2. Collectively, these animal viruses did not fully adapt to spread or cause severe diseases, thus causing successful zoonoses in humans. We believe that this experimental framework provides a path to identifying animal coronaviruses with the potential to cause future zoonoses. IMPORTANCE Evaluation of the zoonotic risk of animal SARSr-CoVs is important for future disease preparedness. However, there are misconceptions regarding the risk of animal viruses. For example, an animal SARSr-CoV could readily infect humans. Alternately, human receptor usage may result in spillover risk. Here, we established an analytical framework to assess the zoonotic risk of SARSr-CoV by testing a series of virus-host interaction profiles. Our data showed that the pre-emergent bat BtCoV-WIV1 and pangolin PCoV-GX were less adapted to humans than SARS-CoV-2 was, suggesting that it may be extremely rare for animal SARSr-CoVs to break all bottlenecks and cause successful zoonoses.

Research on the Characteristics of Safety Culture and Obstacle Factors among Residents under the Influence of COVID-19 in China.

This study established a comprehensive evaluation indicator model for the safety culture among residents during COVID-19 and an obstacle degree model for the identification of the major factors affecting the residents' safety culture. The results show that the overall level of the safety culture among residents was 0.6059. Safety education, channels for learning knowledge regarding safety, and implementation of safety management systems are currently the major obstacles affecting safety culture among residents, but there is still space for improvement in the future. Furthermore, the level of safety culture was strongly related to the distance from the infected, because this changes the risk of viral infection. There are also differences in obstacle factors in different regions. Therefore, it is necessary to implement measures targeting the improvement of safety culture in accordance with the risk of viral infection. Strategies for strengthening the safety culture are also given in this study for consideration in strategic decision making with the aim of promoting the improvement of safety culture among residents, which may help to reduce the risk of infection with COVID-19 for residents.

The Impact of Preventive Strategies Adopted during Large Events on the COVID-19 Pandemic: A Case Study of the Tokyo Olympics to Provide Guidance for Future Large Events.

This study aimed to analyze the impact of hosting large events on the spread of pandemics, taking Tokyo Olympics 2020 as a case study. A risk assessment method for the whole organization process was established, which could be used to evaluate the effectiveness of various risk mitigation measures. Different scenarios for Games participants and Japanese residents during the Tokyo Olympics were designed based on the infection control protocols proposed by the Olympic Committee and local governments. A modified Wells-Riley model considering the influence of social distance, masking and vaccination, and an SIQRV model that introduced the effect of quarantine and vaccination strategies on the pandemic spread were developed in this study. Based on the two models, our predicted results of daily confirmed cases and cumulative cases were obtained and compared with reported data, where good agreement was achieved. The results show that the two core infection control strategies of the bubble scheme and frequent testing scheme curbed the spread of the COVID-19 pandemic during the Tokyo Olympics. Among Games participants, Japanese local staff accounted for more than 60% of the total in positive cases due to their large population and most relaxed travel restrictions. The surge in positive cases was mainly attributed to the high transmission rate of the Delta variant and the low level of immunization in Japan. Based on our simulation results, the risk management flaws for the Tokyo Olympics were identified and improvement measures were investigated. Moreover, a further analysis was carried out on the impact of different preventive measures with respect to minimizing the transmission of new variants with higher transmissibility. Overall, the findings in this study can help policymakers to design scientifically based and practical countermeasures to cope with pandemics during the hosting of large events.