An inducible hACE2 transgenic mouse model recapitulates SARS-CoV-2 infection and pathogenesis in vivo.

The classical manifestation of COVID-19 is pulmonary infection. After host cell entry via human angiotensin-converting enzyme II (hACE2), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can infect pulmonary epithelial cells, especially the AT2 (alveolar type II) cells that are crucial for maintaining normal lung function. However, previous hACE2 transgenic models have failed to specifically and efficiently target the cell types that express hACE2 in humans, especially AT2 cells. In this study, we report an inducible, transgenic hACE2 mouse line and showcase three examples for specifically expressing hACE2 in three different lung epithelial cells, including AT2 cells, club cells, and ciliated cells. Moreover, all these mice models develop severe pneumonia after SARS-CoV-2 infection. This study demonstrates that the hACE2 model can be used to precisely study any cell type of interest with regard to COVID-19-related pathologies.

VR-Enhanced Cognitive Learning: Method, Framework, and Application

Both constructivist learning and situation-cognitive learning believe that learning outcomes are significantly affected by the context or learning environments. However, since 2019, the world has been ravaged by COVID-19. Under the threat of the virus, many offline activities, such as some practical or engineering courses, have been subjected to certain restrictions. Virtual Reality (VR) is an emerging, promising, and rapidly developing technology that enables users to obtain a near-real immersion experience by combining technologies such as computer science, communication, vision, etc. In the context of COVID-19, the advantages of VR immersive experiences are highlighted. By constructing a virtual learning environment, VR technology can greatly compensate for the shortage of traditional teaching conditions and help learners to carry out cognitive learning better. However, currently, VR-enhanced cognitive learning is still in its infancy, along with numerous problems and limitations. Therefore, this paper first conducted an in-depth study of some related concepts, such as constructivist learning and situated cognition learning. Then it proposes a general VR-enhanced cognitive learning framework and designs the general steps for constructing learning situations with VR technology. Based on the proposed model and framework, it developed a campus knowledge-learning APP using VR tools. Through a case study, it verified the validity and performance of the model and strategies. Questionnaire survey and experimental results show that the new model achieves a good learning effect and improves the efficiency of learning by at least 20% compared to the traditional learning methods.

Enhanced fitness of SARS-CoV-2 B.1.617.2 Delta variant in ferrets.

Competition assays were conducted in vitro and in vivo to examine how the Delta (B.1.617.2) variant displaced the prototype Washington/1/2020 (WA/1) strain. While WA/1 virus exhibited a moderately increased proportion compared to that in the inoculum following co-infection in human respiratory cells, Delta variant possessed a substantial in vivo fitness advantage as this virus becoming predominant in both inoculated and contact animals. This work identifies critical traits of the Delta variant that likely played a role in it becoming a dominant variant and highlights the necessities of employing multiple model systems to assess the fitness of newly emerged SARS-CoV-2 variants.

COVID-19 risk perception and tourist satisfaction: A mixed-method study of the roles of destination image and self-protection behavior.

This study aimed to examine the effects of COVID-19 risk perception on negative destination image and self-protection behavior, and the resultant effects on tourist satisfaction. Hence, this study applied a continuous interpretive mixed-method design combining quantitative and qualitative analyses. A quantitative survey (n = 486) in the cities of Ningbo, Huangshan, and Chengdu, China, and 19 qualitative interviews were conducted online. The results of the quantitative study show that: (1) Risk perception and negative destination image are antecedent variables influencing tourist satisfaction, and (2) there are significant positive correlations between risk perception and negative destination image, risk perception and tourist self-protection behavior, and negative destination image and tourist self-protection behavior. Moreover, (3) negative destination image had a partial mediating effect between risk perception and satisfaction. Furthermore, to supplement the research data and expand the quantitative findings, this study further examined whether the above variables are related to tourist satisfaction, through in-depth interviews with tourists. The findings showed that COVID-19 risk perception, negative destination image, and self-protection behavior all affect tourist satisfaction. The findings provide valuable crisis management suggestions for the government and should contribute to the efforts of tourist destinations to build a healthy and safe image, thereby contributing to the sustainable development of tourism industries in the post-epidemic era.

Distinct in vitro and in vivo neutralization profiles of monoclonal antibodies elicited by the receptor binding domain of the ancestral SARS-CoV-2.

Broadly neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are sought to curb coronavirus disease 2019 (COVID-19) infections. Here we produced and characterized a set of mouse monoclonal antibodies (mAbs) specific for the ancestral SARS-CoV-2 receptor binding domain (RBD). Two of them, 17A7 and 17B10, were highly potent in microneutralization assay with 50% inhibitory concentration (IC50 ) ≤135 ng/mL against infectious SARS-CoV-2 variants, including G614, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Kappa, Lambda, B.1.1.298, B.1.222, B.1.5, and R.1. Both mAbs (especially 17A7) also exhibited strong in vivo efficacy in protecting K18-hACE2 transgenic mice from the lethal infection with G614, Alpha, Beta, Gamma, and Delta viruses. Structural analysis indicated that 17A7 and 17B10 target the tip of the receptor binding motif in the RBD-up conformation. A third RBD-reactive mAb (3A6) although escaped by Beta and Gamma, was highly effective in cross-neutralizing Delta and Omicron BA.1 variants in vitro and in vivo. In competition experiments, antibodies targeting epitopes similar to these 3 mAbs were rarely enriched in human COVID-19 convalescent sera or postvaccination sera. These results are helpful to inform new antibody/vaccine design and these mAbs can be useful tools for characterizing SARS-CoV-2 variants and elicited antibody responses.

Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants.

SARS-CoV-2 variants have emerged with elevated transmission and a higher risk of infection for vaccinated individuals. We demonstrate that a recombinant prefusion-stabilized spike (rS) protein vaccine based on Beta/B.1.351 (rS-Beta) produces a robust anamnestic response in baboons against SARS-CoV-2 variants when given as a booster one year after immunization with NVX-CoV2373. Additionally, rS-Beta is highly immunogenic in mice and produces neutralizing antibodies against WA1/2020, Beta/B.1.351, and Omicron/BA.1. Mice vaccinated with two doses of Novavax prototype NVX-CoV2373 (rS-WU1) or rS-Beta alone, in combination, or heterologous prime-boost, are protected from challenge. Virus titer is undetectable in lungs in all vaccinated mice, and Th1-skewed cellular responses are observed. We tested sera from a panel of variant spike protein vaccines and find broad neutralization and inhibition of spike:ACE2 binding from the rS-Beta and rS-Delta vaccines against a variety of variants including Omicron. This study demonstrates that rS-Beta vaccine alone or in combination with rS-WU1 induces antibody-and cell-mediated responses that are protective against challenge with SARS-CoV-2 variants and offers broader neutralizing capacity than a rS-WU1 prime/boost regimen alone. Together, these nonhuman primate and murine data suggest a Beta variant booster dose could elicit a broad immune response to fight new and future SARS-CoV-2 variants.

Impacts of Omicron associated restrictions on vertical distributions of air pollution at a suburb site in Shanghai

To prevent the Omicron transmission, Shanghai government implemented varying degrees of restraint measures. This study provided a new insight into the responses of air pollution altitude dependence to restraint measures by conducting vertical observations at a suburb site in Shanghai. Based on the difference-in-differences (DiD) models that compare the results in 2021 (normal scenario) and 2022 (Omicron-based restriction), we evaluated the casual effects of restrictions on (i) nitrogen dioxide (NO 2), (ii) aerosol (presented by aerosol extinction coefficient (AEC)), formaldehyde (HCHO) and glyoxal (CHOCHO) and (iii) ozone (O 3), which are generally treaded as primary, multi-sources and secondary pollutants, respectively. The estimated results from 0.0 to 2.0 km show that the drop/rise induced by restrictions is greater below 1.0 km than that above 1.0 km. Averaged on vertical distributions, AEC, NO 2 , HCHO and CHOCHO during restrictions felled by 15.1% (0.12 km−1), 40.3% (1.65 ppbv), 10.0% (0.26 ppbv) and 28.6% (21.79 pptv), respectively, while O 3 increased by 21.3% (18.12 μg/m3). It indicates that restrictions induce significant drops in primary pollutants and enhancements in secondary pollutants. For multi-sources pollutants, the decline from primary sources can be partly offset by enhanced secondary productions, and the ratio of increased secondary sources to decreased primary sources can be elevated with height. The discrepancies of responses to restrictions are reflected in vertical distribution and types of air pollution, emphasizing the significance of vertical observations for diversified pollution. These finding can also be meaningful in the strategy development for prevention and control of air pollution. [Display omitted] • This study provided a new insight into the responses of air pollution altitude dependence to restraint measures by employing vertical observations. • The difference-in differences model was applied to evaluate the casual effects of restrictions on different types of pollution. • The decline of multi-sources pollutants from primary sources can be partly offset by enhanced secondary productions. [ FROM AUTHOR]

Cross-neutralization and viral fitness of SARS-CoV-2 Omicron sublineages.

The rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better understanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fitness and antigenic relationship among Omicron sublineages. In both K18-hACE2 mice and human airway cultures, Omicron sublineages exhibited a replication order of BA.5 ≥ BA.2 ≥ BA.2.12.1 > BA.1; no difference in body weight loss was observed among different sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice developed distinguishable cross-neutralizations against Omicron sublineages, but exhibited little neutralization against the index virus (i.e. USA-WA1/2020) or the Delta variant. Surprisingly, the BA.5-infected mice developed higher neutralization activity against heterologous BA.2 and BA.2.12.1 than that against homologous BA.5; serum neutralizing titres did not always correlate with viral replication levels in infected animals. Our results revealed a distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach.

Association of Culturable-Virus Detection and Household Transmission of SARS-CoV-2, California and Tennessee, 2020-2022.

From 2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) household transmission studies (enrolling April 2020 to January 2022) with rapid enrollment and specimen collection for 14 days, 61% (43/70) of primary cases had culturable virus detected ≥6 days post-onset. Risk of secondary infection among household contacts tended to be greater when primary cases had culturable virus detected after onset. Regardless of duration of culturable virus, most secondary infections (70%, 28/40) had serial intervals <6 days, suggesting early transmission. These data examine viral culture as a proxy for infectiousness, reaffirm the need for rapid control measures after infection, and highlight the potential for prolonged infectiousness (≥6 days) in many individuals.

Ozone Pollution of Megacity Shanghai during City-Wide Lockdown Assessed Using TROPOMI Observations of NO2 and HCHO

An unprecedented city-wide lockdown took place in Shanghai from April to May 2022 to curb the spread of COVID-19, which caused socio-economic disruption but a significant reduction of anthropogenic emissions in this metropolis. However, the ground-based monitoring data showed that the concentration of ozone (O3) remained at a high level. This study applied Tropospheric Monitoring Instrument (TROPOMI) observations to examine changes in tropospheric vertical column density (VCD) of nitrogen dioxide (NO2) and formaldehyde (HCHO), which are precursors of O3. Compared with the same period in 2019-2021, VCDs of NO2 and HCHO decreased respectively by ~50% and ~20%. Multiple regression analysis showed that the lockdown effect played a dominant role in this dramatic decline rather than meteorological impacts. Using the exponentially-modified Gaussian method, this study quantified nitrogen oxides (NOX) emission in Shanghai as 32.60 mol/s with a decrease of 50-80%, which was mainly contributed by the transportation and industrial sectors. The significant reduction of NOX emission in Shanghai is much higher than that of volatile organic compounds (VOCs), which led to dramatic changes in formaldehyde-to-nitrogen dioxide ratio (HCHO/NO2, FNR). Thus, when enforcing regulation on NOx emission control in the future, coordinately reducing VOCs emission should be implemented to mitigate urban O3 pollution.

Detection of Airborne Influenza A and SARS-CoV-2 Virus Shedding following Ocular Inoculation of Ferrets.

Despite reports of confirmed human infection following ocular exposure with both influenza A virus (IAV) and SARS-CoV-2, the dynamics of virus spread throughout oculonasal tissues and the relative capacity of virus transmission following ocular inoculation remain poorly understood. Furthermore, the impact of exposure route on subsequent release of airborne viral particles into the air has not been examined previously. To assess this, ferrets were inoculated by the ocular route with A(H1N1)pdm09 and A(H7N9) IAVs and two SARS-CoV-2 (early pandemic Washington/1 and Delta variant) viruses. Virus replication was assessed in both respiratory and ocular specimens, and transmission was evaluated in direct contact or respiratory droplet settings. Viral RNA in aerosols shed by inoculated ferrets was quantified with a two-stage cyclone aerosol sampler (National Institute for Occupational Safety and Health [NIOSH]). All IAV and SARS-CoV-2 viruses mounted a productive and transmissible infection in ferrets following ocular inoculation, with peak viral titers and release of virus-laden aerosols from ferrets indistinguishable from those from ferrets inoculated by previously characterized intranasal inoculation methods. Viral RNA was detected in ferret conjunctival washes from all viruses examined, though infectious virus in this specimen was recovered only following IAV inoculation. Low-dose ocular-only aerosol exposure or inhalation aerosol exposure of ferrets to IAV similarly led to productive infection of ferrets and shedding of aerosolized virus. Viral evolution during infection was comparable between all inoculation routes examined. These data support that both IAV and SARS-CoV-2 can establish a high-titer mammalian infection following ocular exposure that is associated with rapid detection of virus-laden aerosols shed by inoculated animals. IMPORTANCE Documented human infection with influenza viruses and SARS-CoV-2 has been reported among individuals wearing respiratory protection in the absence of eye protection, highlighting the capacity of these respiratory tract-tropic viruses to exploit nonrespiratory routes of exposure to initiate productive infection. However, comprehensive evaluations of how ocular exposure may modulate virus pathogenicity and transmissibility in mammals relative to respiratory exposure are limited and have not investigated multiple virus families side by side. Using the ferret model, we show that ocular exposure with multiple strains of either coronaviruses or influenza A viruses leads to an infection that results in shedding of detectable aerosolized virus from inoculated animals, contributing toward onward transmission of both viruses to susceptible contacts. Collectively, these studies support that the ocular surface represents a susceptible mucosal surface that, if exposed to a sufficient quantity of either virus, permits establishment of an infection which is similarly transmissible as that following respiratory exposure.

Impacts of Omicron associated restrictions on vertical distributions of air pollution at a suburb site in Shanghai

To prevent the Omicron transmission, Shanghai government implemented varying degrees of restraint measures. This study provided a new insight into the responses of air pollution altitude dependence to restraint measures by conducting vertical observations at a suburb site in Shanghai. Based on the difference-in-differences (DiD) models that compare the results in 2021 (normal scenario) and 2022 (Omicron-based restriction), we evaluated the casual effects of restrictions on (i) nitrogen dioxide (NO2), (ii) aerosol (presented by aerosol extinction coefficient (AEC)), formaldehyde (HCHO) and glyoxal (CHOCHO) and (iii) ozone (O3), which are generally treaded as primary, multi-sources and secondary pollutants, respectively. The estimated results from 0.0 to 2.0 km show that the drop/rise induced by restrictions is greater below 1.0 km than that above 1.0 km. Averaged on vertical distributions, AEC, NO2, HCHO and CHOCHO during restrictions felled by 15.1% (0.12 km−1), 40.3% (1.65 ppbv), 10.0% (0.26 ppbv) and 28.6% (21.79 pptv), respectively, while O3 increased by 21.3% (18.12 μg/m3). It indicates that restrictions induce significant drops in primary pollutants and enhancements in secondary pollutants. For multi-sources pollutants, the decline from primary sources can be partly offset by enhanced secondary productions, and the ratio of increased secondary sources to decreased primary sources can be elevated with height. The discrepancies of responses to restrictions are reflected in vertical distribution and types of air pollution, emphasizing the significance of vertical observations for diversified pollution. These finding can also be meaningful in the strategy development for prevention and control of air pollution.

Surveillance and Correlation of Severe Acute Respiratory Syndrome Coronavirus 2 Viral RNA, Antigen, Virus Isolation, and Self-Reported Symptoms in a Longitudinal Study With Daily Sampling.

The novel coronavirus pandemic incited unprecedented demand for assays that detect viral nucleic acids, viral proteins, and corresponding antibodies. The 320 molecular diagnostics in receipt of US Food and Drug Administration emergency use authorization mainly focus on viral detection; however, no currently approved test can be used to infer infectiousness, that is, the presence of replicable virus. As the number of tests conducted increased, persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA positivity by reverse-transcription polymerase chain reaction (RT-PCR) in some individuals led to concerns over quarantine guidelines. To this end, we attempted to design an assay that reduces the frequency of positive test results from individuals who do not shed culturable virus. We describe multiplex quantitative RT-PCR assays that detect genomic RNA (gRNA) and subgenomic RNA (sgRNA) species of SARS-CoV-2, including spike, nucleocapsid, membrane, envelope, and ORF8. Viral RNA abundances calculated from these assays were compared with antigen presence, self-reported symptoms, and culture outcome (virus isolation) using samples from a 14-day longitudinal household transmission study. By characterizing the clinical and molecular dynamics of infection, we show that sgRNA detection has higher predictive value for culture outcome compared to detection of gRNA alone. Our findings suggest that sgRNA presence correlates with active infection and may help identify individuals shedding culturable virus.

Enhanced virulence and waning vaccine-elicited antibodies account for breakthrough infections caused by SARS-CoV-2 delta and beyond.

Here we interrogate the factors responsible for SARS-CoV-2 breakthrough infections in a K18-hACE2 transgenic mouse model. We show that Delta and the closely related Kappa variant cause viral pneumonia and severe lung lesions in K18-hACE2 mice. Human COVID-19 mRNA post-vaccination sera after the 2nd dose are significantly less efficient in neutralizing Delta/Kappa than early 614G virus in vitro and in vivo. By 5 months post-vaccination, ≥50% of donors lack detectable neutralizing antibodies against Delta and Kappa and all mice receiving 5-month post-vaccination sera die after the lethal challenges. Although a 3rd vaccine dose can boost antibody neutralization against Delta in vitro and in vivo, the mean log neutralization titers against the latest Omicron subvariants are 1/3-1/2 of those against the original 614D virus. Our results suggest that enhanced virulence, greater immune evasion, and waning of vaccine-elicited protection account for SARS-CoV-2 variants caused breakthrough infections.

Comparative Assessment of Severe Acute Respiratory Syndrome Coronavirus 2 Variants in the Ferret Model.

The continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans necessitates evaluation of variants for enhanced virulence and transmission. We used the ferret model to perform a comparative analysis of four SARS-CoV-2 strains, including an early pandemic isolate from the United States (WA1), and representatives of the Alpha, Beta, and Delta lineages. While Beta virus was not capable of pronounced replication in ferrets, WA1, Alpha, and Delta viruses productively replicated in the ferret upper respiratory tract, despite causing only mild disease with no overt histopathological changes. Strain-specific transmissibility was observed; WA1 and Delta viruses transmitted in a direct contact setting, whereas Delta virus was also capable of limited airborne transmission. Viral RNA was shed in exhaled air particles from all inoculated animals but was highest for Delta virus. Prior infection with SARS-CoV-2 offered varied protection against reinfection with either homologous or heterologous variants. Notable genomic variants in the spike protein were most frequently detected following WA1 and Delta virus infection. IMPORTANCE Continued surveillance and risk assessment of emerging SARS-CoV-2 variants are critical for pandemic response and preparedness. As such, in vivo evaluations are indispensable for early detection of variants with enhanced virulence and transmission. Here, we used the ferret model to compare the pathogenicity and transmissibility of an original SARS-CoV-2 isolate (USA-WA1/2020 [WA1]) to those of a panel of Alpha, Beta, and Delta variants, as well as to evaluate protection from homologous and heterologous reinfection. We observed strain-specific differences in replication kinetics in the ferret respiratory tract and virus load emitted into the air, revealing enhanced transmissibility of the Delta virus relative to previously detected strains. Prior infection with SARS-CoV-2 provided varied levels of protection from reinfection, with the Beta strain eliciting the lowest level of protection. Overall, we found that ferrets represent a useful model for comparative assessments of SARS-CoV-2 infection, transmission, and reinfection.

Evaluating the Spatial Risk of Bacterial Foodborne Diseases Using Vulnerability Assessment and Geographically Weighted Logistic Regression

Foodborne diseases are an increasing concern to public health;climate and socioeconomic factors influence bacterial foodborne disease outbreaks. We developed an “exposure–sensitivity–adaptability” vulnerability assessment framework to explore the spatial characteristics of multiple climatic and socioeconomic environments, and analyzed the risk of foodborne disease outbreaks in different vulnerable environments of Zhejiang Province, China. Global logistic regression (GLR) and geographically weighted logistic regression (GWLR) models were combined to quantify the influence of selected variables on regional bacterial foodborne diseases and evaluate the potential risk. GLR results suggested that temperature, total precipitation, road density, construction area proportions, and gross domestic product (GDP) were positively correlated with foodborne diseases. GWLR results indicated that the strength and significance of these relationships varied locally, and the predicted risk map revealed that the risk of foodborne diseases caused by Vibrio parahaemolyticus was higher in urban areas (60.6%) than rural areas (20.1%). Finally, distance from the coastline was negatively correlated with predicted regional risks. This study provides a spatial perspective for the relevant departments to prevent and control foodborne diseases.

Impact Assessment of COVID-19 Lockdown on Vertical Distributions of NO2 and HCHO From MAX-DOAS Observations and Machine Learning Models.

Responses to the COVID-19 pandemic led to major reductions on air pollutant emissions in modern history. To date, there has been no comprehensive assessment for the impact of lockdowns on the vertical distributions of nitrogen dioxide (NO2) and formaldehyde (HCHO). Based on profiles from 0 to 2 km retrieved by Multi-AXis-Differential Optical Absorption Spectroscopy observation and a large volume of real-time data at a suburb site in Shanghai, China, four types of machine learning models were developed and compared, including multiple linear regression, support vector machine, bagged trees (BT), and artificial neural network. Ultimately BT model was employed to reproduce NO2 and HCHO profiles with the best performance. Predictions with different meteorological and surface pollution scenarios were conducted from 2017 to 2019, for assessing the corresponding impacts on the changes of NO2 and HCHO profiles during COVID-19 lockdown. The simulations illustrate that the NO2 decreased in 2020 by 43.8%, 45.5%, and 44.6%, relative to 2017, 2018, and 2019, respectively. For HCHO, the lockdown-induced situation presented the declines of 28.6%, 32.1%, and 10.9%, respectively. In the comparisons of vertical distributions, NO2 maintained decreasing at all altitudes, while HCHO decreased at low altitudes and increased at high altitudes. During COVID-19 lockdown, the reduction of NO2 and HCHO from the variation of surface pollutants was dominated below 0.5 km, while the relevant meteorological factors played a more significant role above 0.5 km.

Safety and immunogenicity following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): a secondary analysis of a randomised, placebo-controlled, phase 2 trial.

BACKGROUND: Emerging SARS-CoV-2 variants and evidence of waning vaccine efficacy present substantial obstacles towards controlling the COVID-19 pandemic. Booster doses of SARS-CoV-2 vaccines might address these concerns by amplifying and broadening the immune responses seen with initial vaccination regimens. We aimed to assess the immunogenicity and safety of a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373). METHODS: This secondary analysis of a phase 2, randomised study assessed a single booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-M adjuvant (NVX-CoV2373) in healthy adults aged 18-84 years, recruited from 17 clinical centres in the USA and Australia. Eligible participants had a BMI of 17-35 kg/m² and, for women, were heterosexually inactive or using contraception. Participants who had a history of SARS-CoV or SARS-CoV-2, confirmed diagnosis of COVID-19, serious chronic medical conditions, or were pregnant or breastfeeding were excluded. Approximately 6 months following their primary two-dose vaccination series (administered day 0 and day 21), participants who received placebo for their primary vaccination series received a placebo booster (group A) and participants who received NVX-CoV2373 for their primary vaccination series (group B) were randomly assigned (1:1) again, via centralised interactive response technology system, to receive either placebo (group B1) or a single booster dose of NVX-CoV2373 (5 µg SARS-CoV-2 rS with 50 µg Matrix-M adjuvant; group B2) via intramuscular injection; randomisation was stratified by age and study site. Vaccinations were administered by designated site personnel who were masked to treatment assignment, and participants and other site staff were also masked. Administration personnel also assessed the outcome. The primary endpoints are safety (unsolicited adverse events) and reactogenicity (solicited local and systemic) events and immunogenicity (serum IgG antibody concentrations for the SARS-CoV-2 rS protein antigen) assessed 14 days after the primary vaccination series (day 35) and 28 days following booster (day 217). Safety was analysed in all participants in groups A, B1, and B2, according to the treatment received; immunogenicity was analysed in the per-protocol population (ie, participants in groups A, B1, and B2) who received all assigned doses and who did not test SARS-CoV-2-positive or received an authorised vaccine, analysed according to treatment assignment). This trial is registered with ClinicalTrials.gov, NCT04368988. FINDINGS: 1610 participants were screened from Aug 24, 2020, to Sept 25, 2020. 1282 participants were enrolled, of whom 173 were assigned again to placebo (group A), 106 were re-randomised to NVX-CoV2373-placebo (group B1), and 104 were re-randomised to NVX-CoV2373-NVX-CoV2373 (group B2); after accounting for exclusions and incorrect administration, 172 participants in group A, 102 in group B1, and 105 in group B2 were analysed for safety. Following the active booster, the proportion of participants with available data reporting local (80 [82%] of 97 participants had any adverse event; 13 [13%] had a grade ≥3 event) and systemic (75 [77%] of 98 participants had any adverse event; 15 [15%] had a grade ≥3 event) reactions was higher than after primary vaccination (175 [70%] of 250 participants had any local adverse event, 13 [5%] had a grade ≥3 event; 132 [53%] of 250 had any systemic adverse event, 14 [6%] had a grade ≥3 event). Local and systemic events were transient in nature (median duration 1·0-2·5 days). In the per-protocol immunogenicity population at day 217 (167 participants in group A, 101 participants in group B1, 101 participants in group B2), IgG geometric mean titres (GMT) had increased by 4·7-fold and MN₅₀ GMT by 4·1-fold for the ancestral SARS-CoV-2 strain compared with the day 35 titres. INTERPRETATION: Administration of a booster dose of NVX-CoV2373 resulted in an incremental increase in reactogenicity. For both the prototype strain and all variants evaluated, immune responses following the booster were similar to or higher than those associated with high levels of efficacy in phase 3 studies of the vaccine. These data support the use of NVX-CoV2373 in booster programmes. FUNDING: Novavax and the Coalition for Epidemic Preparedness Innovations.

Perceived Benefits and Forest Tourists Consumption Intention: Environmental Protection Attitude and Resource Utilization Attitude as Mediators

Establishing a relationship model between environmental protection and resource utilization attitude and consumption intention is the key to promoting the sustainable development of forest tourism. From the standpoint of the Stimulus–Organism–Response (SOR) framework, the purpose of this study is to explore the complex causal relationships between perceived benefits, attitudes toward environmental protection, resource utilization attitudes, and consumption intentions in the context of forest tourism. The research data have been collected using a questionnaire survey of 436 tourists at Siming Mountain in the suburbs of Ningbo city, China. Furthermore, it is analyzed by structural equation modeling. The results indicate a positive correlation between the perceived benefits and tourists’ consumption intention that is mediated by the tourists’ attitude toward resource utilization. Although the independent mediating effect of environmental protection attitude is not supported in this study, both attitudes have played a chain-mediating role between perceived benefit and consumption intention. This study contributes to the existing knowledge by measuring the impact of perceived benefits and environmental attitudes of forest tourists on consumption intentions.

Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension.

High blood pressure is one of the most important risk factors for ischaemic heart disease, stroke, other cardiovascular diseases, chronic kidney disease and dementia. Mean blood pressure and the prevalence of raised blood pressure have declined substantially in high-income regions since at least the 1970s. By contrast, blood pressure has risen in East, South and Southeast Asia, Oceania and sub-Saharan Africa. Given these trends, the prevalence of hypertension is now higher in low-income and middle-income countries than in high-income countries. In 2015, an estimated 8.5 million deaths were attributable to systolic blood pressure >115 mmHg, 88% of which were in low-income and middle-income countries. Measures such as increasing the availability and affordability of fresh fruits and vegetables, lowering the sodium content of packaged and prepared food and staples such as bread, and improving the availability of dietary salt substitutes can help lower blood pressure in the entire population. The use and effectiveness of hypertension treatment vary substantially across countries. Factors influencing this variation include a country's financial resources, the extent of health insurance and health facilities, how frequently people interact with physicians and non-physician health personnel, whether a clear and widely adopted clinical guideline exists and the availability of medicines. Scaling up treatment coverage and improving its community effectiveness can substantially reduce the health burden of hypertension.