Risk Spillover Effects of International Risk Factors on China's Energy Market - Based on Geopolitical Threats and Shipping Markets (preprint)

Risks caused by geo-risk cases, such as regional conflicts, propagate around the world, and this study provides insights into the dynamic and complex interactions of risks between international geopolitical risks, international shipping markets, China's carbon market, and the energy sector. The findings show that international geopolitical risk and international shipping markets are net transmitters of risk with positive net spillover values, indicating that they tend to export risk volatility to other markets. In contrast, the Chinese carbon market and the markets of traditional energy and high-emission sectors exhibit amplified volatility in the face of extreme risk events such as the COVID-19 pandemic, the Russian-Ukrainian conflict and the Israeli-Palestinian conflict. This highlights the time-varying nature of risk spillovers in these markets. Notably, the peaks in net spillovers from the Geopolitical Risk Index to the Baltic Dry Index and Shanghai crude oil futures suggest a direct correlation with geopolitical tensions affecting the oil and shipping industries, such as conflicts in oil-rich regions or maritime disputes affecting shipping lanes. These findings highlight the mediating role of international shipping in the transmission of geopolitical risks to regional markets. The paper concludes with policy recommendations for predicting and mitigating the impact of geopolitical uncertainty and shipping markets on energy markets.

Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial-First progress report.

High blood pressure (BP) and type-2 diabetes (T2DM) are forerunners of chronic kidney disease and left ventricular dysfunction. Home BP telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling risk stratification and personalized prevention. UPRIGHT-HTM (NCT04299529) is an investigator-initiated, multicenter, open-label, randomized trial with blinded endpoint evaluation designed to assess the efficacy of HTM plus UPP (experimental group) over HTM alone (control group) in guiding treatment in asymptomatic patients, aged 55-75 years, with ≥5 cardiovascular risk factors. From screening onwards, HTM data can be freely accessed by all patients and their caregivers; UPP results are communicated early during follow-up to patients and caregivers in the intervention group, but at trial closure in the control group. From May 2021 until January 2023, 235 patients were screened, of whom 53 were still progressing through the run-in period and 144 were randomized. Both groups had similar characteristics, including average age (62.0 years) and the proportions of African Blacks (81.9%), White Europeans (16.7%), women 56.2%, home (31.2%), and office (50.0%) hypertension, T2DM (36.4%), micro-albuminuria (29.4%), and ECG (9.7%) and echocardiographic (11.5%) left ventricular hypertrophy. Home and office BP were 128.8/79.2 mm Hg and 137.1/82.7 mm Hg, respectively, resulting in a prevalence of white-coat, masked and sustained hypertension of 40.3%, 11.1%, and 25.7%. HTM persisted after randomization (48 681 readings up to 15 January 2023). In conclusion, results predominantly from low-resource sub-Saharan centers proved the feasibility of this multi-ethnic trial. The COVID-19 pandemic caused delays and differential recruitment rates across centers.

Financial relief policy and social distancing during the COVID-19 pandemic

In this paper, we investigate the effect of stimulus payments during the COVID-19 pandemic on the social distancing practices of their recipients. While the directed cash payments stipulated by the 2020 CARES Act were intended to mitigate the economic impact of closures imposed in response to the outbreak, we find that this relief may also have inadvertently contributed to the spread of the virus due to increased social activity. We find that, as the payments were sent out on a staggered weekly schedule, there was a corresponding spike in weekend traffic as indicated by a number of mobility metrics that measure social distancing, over and above the usual uptick expected from weekend shopping following receipt of the stimulus payments on Fridays. This preliminary study gives some indication that the economic benefits of the stimulus package may in fact be outweighed by the detrimental effects of looser social distancing practices prolonging the outbreak.

The changes in job-housing balance during the Covid-19 period in China.

By using three continuous years of national-scale cellphone signaling data from Jan. 2019 to Dec. 2021, this study adds fresh evidence for job-housing balance changes at the Quxian level during the COVID-19 period in China. The findings show that according to the resident-balance index and worker-balance index, the job-housing balance jumped when the number of COVID-19 confirmed cases reached its peak in February 2020, with an average of 94.4 % which is the highest level during these three years. The study also found that the Quxian-level job-housing balance has generally improved steadily in the two years of the pandemic. In addition, the results highlighted the huge gaps between females and males in the job-housing balance, but the gender disparities in job-housing balance were reduced to a minimum during the pandemic lockdown. In addition, by comparison analysis of the changes in resident-balance index and worker-balance index during this unprecedented crisis, this study found that for Quxians with high economic vitality, worker-balance index increased greater than resident-balance index, but for Quxians with low economic vitality, the reverse happened. Our findings provide a better understanding of the job-housing relationship during public health crises that can support the urban management in the future policymaking.

Emotional disturbance and risk factors among COVID-19 confirmed cases in isolation hotels.

Patients with coronavirus disease 2019 (COVID-19) has been isolated in hospital-managed isolation hotels under a policy of the Taiwan government. Centrally isolation patients are more likely to experience psychological symptoms. The purpose of the study was to investigate emotional disturbance during their isolation period and then pinpoint the factors during their isolation period associated with the emotional disturbance. We retrospectively analysed the medical charts of the patients confined to a Banqiao isolation hotel between May 28 and July 3, 2021. The 5-item brief symptom rating scale (BSRS-5) was used to evaluate emotional disturbance levels. Descriptive and logistic regression was used for the data analysis. In total, 197 complete medical records were reviewed, and of these 84 (42.6%) showed emotional disturbance. The majority of them reported only minor disturbance (n = 49, 58.3%). After controlling for confounding factors, being satisfied about medical information was the only protective factor associated with emotional disturbance (OR = 0.2, P = 0.018). Being a male patient (OR = 3.0, P = 0.005), worrying about stigmatization (OR = 2.2, P = 0.041) and being unable to contact family members (OR = 2.9, P = 0.018) increased the risk of experiencing emotional disturbance. Patients with clinical symptoms, namely sore throat (OR = 3.4, P = 0.013) and muscle aches (OR = 6.3, P = 0.005), were also found to be more likely to report emotional disturbance. Mental disturbance commonly occurs among patient with COVID-19 who are isolated in a hospital-managed hotel. Being a male patient, having symptoms, namely a sore throat and muscle pain, being unable to contact family and/or a failure to receive sufficient medical information were found to be associated with emotional disturbance. In order to help isolated patients, government officials should provide a clear rationale for isolation and recognize the patients' efforts to follow the government's policy, which will help to minimize social stigma.

Durability of neutralization against Omicron subvariants after vaccination and breakthrough infection.

Booster immunizations and breakthrough infections can elicit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4-6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants.

Coronavirus disease 2019: Repeated immersion of chlorine-containing disinfectants has adverse effects on goggles.

Introduction: During COVID-19, some front-line personnel experienced varying degrees of eye discomfort due to the use of goggles repeatedly disinfected with chlorine-containing disinfectant. Methods: The eye damage information of 276 front-line personnel who used goggles in a hospital from October 1, 2021, to December 1, 2021, was collected by filling out a questionnaire. To study the effect of chlorinated disinfectants on goggles, we immersed the goggles in the same volume of water and chlorinated disinfectant buckets. We tested the light transmittance, color and texture, and airtightness of the goggles at different times (1, 3, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240, and 268 h). In addition, we detected where chlorinated disinfectant remained in the goggles by using disinfectant concentration test paper. Results: 60 (21.82%) people experienced dry eyes, stinging pain, photophobia and tearing, conjunctival congestion, eyelid redness, and swelling. After treatment or rest, the patient's ocular symptoms were significantly relieved within 3 days. With the extension of disinfection time, the light transmission of the lenses gradually decreased, and the light transmission reduced when immersion occurred at 216 h. After 72 h of disinfection, the color of the goggle frame began to change to light yellow, the texture gradually became hard and brittle, and the color became significantly darker at 268 h of disinfection. The airtightness of the goggles began to decrease after 168 h of disinfection, the airtightness decreased substantially at 268 h, and the shape changed significantly. In addition, the concentration test paper results show that the disinfection solution mainly resides in the goggle frame seam and goggles' elastic bands' bundle. Conclusions: Repeated chlorine disinfectant disinfection will reduce the effectiveness of goggles protection and damage front-line personnel's eye health.

Changes in tourist mobility after COVID-19 outbreaks.

We comparatively examined tourist mobility changes in the entire country and explicitly covered two distinct waves of COVID-19 outbreaks, based on mobile phone data from 277.15 million tourists from 2019 to 2021 in China. The results show that domestic tourism in Beijing was even higher after the pandemic than prior to it. In addition, we found that female and elderly groups had a slower recovery after the first wave, whereas this was the opposite one year later, after the second wave. Additionally, wealthier, larger cities were notably hit the hardest. Overall, our findings provide a better understanding of tourism management in public health crises and policy-making during post-pandemic recovery and for future outbreaks.

Characterization and pathogenicity of the porcine epidemic diarrhea virus isolated in China.

Piglet diarrhea caused by the porcine epidemic diarrhea virus (PEDV) is a common problem on pig farms in China associated with high morbidity and mortality rates. In this study, three PEDV isolates were successfully detected after the fourth blind passage in Vero cells. The samples were obtained from infected piglet farms in Jilin (Changchun), and Shandong (Qingdao) Provinces of China and were designated as CH/CC-1/2018, CH/CC-2/2018, and CH/QD/2018. According to the analysis of the complete S protein gene sequence, the CH/CC-1/2018 and CH/CC-2/2018 were allocated to the G2b branch, while CH/QD/2018 was located in the G1a interval and was closer to the vaccine strain CV777. Successful detection and identification of the isolated strains were carried out using electron microscopy and indirect immunofluorescence. Meanwhile, animal challenge experiments and viral RNA copies determination were used to compare the pathogenicity. The results showed that CH/CC-1/2018 in Changchun was more pathogenic than CH/QD/2018 in Qingdao. In conclusion, the discovery of these new strains is conducive to the development of vaccines to prevent the pandemic of PEDV, especially that the CH/CC-1/2018, and CH/CC-2/2018 were not related to the classical vaccine strain CV777.

Intelligent and Interactive Chatbot Based on the Recommendation Mechanism to Reach Personalized Learning

With the impacts of Covid-19 epidemic, e-learning has become a popular research issue. Therefore, how to upgrade the interactivity of e-learning, and allow learners to quickly access personalized and popular learning information from huge digital materials, is very important. However, chatbots are mostly used in automation, as well as simple occasions of general standard question and answer. But to solve the different problems of e-learners in the learning process, chatbots are used to filter the blind spots of learners and to provide further relevant information, so that e-learning can improve in efficiency and interactivity. This study utilizes AI, two-stage Bayesian algorithm, and crawler technology to provide customized learning materials according to learner's current learning situation. The experimental results show that this research system can indeed correctly understand and judge the blind spots of digital learners, and effectively find the relevant e-learning and video information. The accuracy rate reaches nearly 90%.

Durability of neutralization against Omicron subvariants after vaccination and breakthrough infection

Booster immunizations and breakthrough infections can elicit SARS-CoV-2 Omicron subvariants neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4–6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of ∼9- to 41-fold, ∼16- to 63-fold, and ∼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants. Graphical Zhu et al. report that a two-dose CoronaVac or ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity and Delta, BA.1 and BA.2 breakthrough infection induce neutralization against earlier Omicron variants, but not for BQ.1.1 and XBB, up to 5 months after vaccination or infection.

Coronavirus disease 2019: Repeated immersion of chlorine-containing disinfectants has adverse effects on goggles

Introduction During COVID-19, some front-line personnel experienced varying degrees of eye discomfort due to the use of goggles repeatedly disinfected with chlorine-containing disinfectant. Methods The eye damage information of 276 front-line personnel who used goggles in a hospital from October 1, 2021, to December 1, 2021, was collected by filling out a questionnaire. To study the effect of chlorinated disinfectants on goggles, we immersed the goggles in the same volume of water and chlorinated disinfectant buckets. We tested the light transmittance, color and texture, and airtightness of the goggles at different times (1, 3, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240, and 268 h). In addition, we detected where chlorinated disinfectant remained in the goggles by using disinfectant concentration test paper. Results 60 (21.82%) people experienced dry eyes, stinging pain, photophobia and tearing, conjunctival congestion, eyelid redness, and swelling. After treatment or rest, the patient's ocular symptoms were significantly relieved within 3 days. With the extension of disinfection time, the light transmission of the lenses gradually decreased, and the light transmission reduced when immersion occurred at 216 h. After 72 h of disinfection, the color of the goggle frame began to change to light yellow, the texture gradually became hard and brittle, and the color became significantly darker at 268 h of disinfection. The airtightness of the goggles began to decrease after 168 h of disinfection, the airtightness decreased substantially at 268 h, and the shape changed significantly. In addition, the concentration test paper results show that the disinfection solution mainly resides in the goggle frame seam and goggles' elastic bands' bundle. Conclusions Repeated chlorine disinfectant disinfection will reduce the effectiveness of goggles protection and damage front-line personnel's eye health.

Brace for Another Crisis: Empirical Evidence from US Construction Industry and Firm Performance during and after 2007–2009 Global Financial Crisis

Despite the strong connection between the construction industry and the economy, very little is known about how a nation's prevailing economic conditions affect the construction industry and firm performance. Building upon economic contagion literature, this research empirically investigates the effect of the 2007–2009 global financial crisis (i.e., prevailing economic conditions) on the United States (US) construction industry and firm performance. The authors performed the analysis of the joint test of contagion, crisis severity index, and student t-test using the daily stock index in the US market and the daily stock prices and annual financial data of 39 selected US construction firms between 1st January 2005 and 31st December 2012, spanning precrisis, crisis and postcrisis periods. The longitudinal empirical data, involving a total of 2084 data points for each firm and the US stock market, confirmed a widespread negative effect of the crisis on the US construction industry in a pattern that is consistent with the occurrence of major events (e.g., the collapse of Lehman Brothers);and this negative effect continued, with a lower level of severity, into the postcrisis period. Within the industry, the highly market-driven homebuilding firms are affected more significantly by the crisis than construction and engineering firms. These time series trends and patterns support the strong construction-economy nexus. Additionally, construction firms with poor financial positions (i.e., profitability, liquidity, leverage, and turnover ratios), especially liquidity positions, are likely to suffer more strongly from the crisis and its residual impact. Thus, to survive, recover from and prepare for future economic disturbances, such as those caused by the COVID-19 pandemic, construction firms should closely monitor and manage their capabilities to generate revenue and repay their debt—that is to maintain sound cash flows. In this regard, practical recommendations are made accordingly. Theoretically, this research contributes to the understanding of the heterogeneous effect of economic conditions on the construction industry and firm performance and its contributing contextual factors. [ FROM AUTHOR]

How do low-income single-mothers get by when unemployment strikes: Patterns of multiple program participation after transition from employment to unemployment.

Little is known about longitudinal patterns of welfare program participation among single mothers after they transition from employment to unemployment. To better understand how utilization patterns of these welfare programs may change during the 12 months after a job loss, we used the 2008 Survey of Income and Program Participation to examine the patterns of participation in Medicaid, the Supplemental Nutrition Assistance Program, Temporary Assistance for Needy Families, and unemployment insurance among 342 single mothers who transitioned from employment to unemployment during the Great Recession. Using sequence analysis and cluster analysis, this paper identified four distinct patterns of program participation: (a) constantly receiving in-kind benefits; (b) primarily but not solely receiving food stamps; (c) inconsistent unemployment insurance or Medicaid-based benefits; and (d) limited or no benefits. Almost two-fifths of our sample of single mothers received inconsistent, limited, or no benefits. Results of the multinomial regression revealed that race, work disability, poverty, homeownership, and region of residence were significant factors that influenced whether study subjects participated in or had access to social safety net programs. Our findings illustrate the heterogeneity in patterns of multiple program participation among single mothers transitioning from employment to unemployment. Better understanding these varied patterns may inform decisions that increase the accessibility of US social safety net programs for single mothers during periods of personal economic hardship.

Financial relief policy and social distancing during the COVID-19 pandemic.

In this paper, we investigate the effect of stimulus payments during the COVID-19 pandemic on the social distancing practices of their recipients. While the directed cash payments stipulated by the 2020 CARES Act were intended to mitigate the economic impact of closures imposed in response to the outbreak, we find that this relief may also have inadvertently contributed to the spread of the virus due to increased social activity. We find that, as the payments were sent out on a staggered weekly schedule, there was a corresponding spike in weekend traffic as indicated by a number of mobility metrics that measure social distancing, over and above the usual uptick expected from weekend shopping following receipt of the stimulus payments on Fridays. This preliminary study gives some indication that the economic benefits of the stimulus package may in fact be outweighed by the detrimental effects of looser social distancing practices prolonging the outbreak.

Predictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection: a prospective multicentre cohort study.

BACKGROUND: The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker. METHODS: CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country. FINDINGS: From June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1-3 in 445 (44%) participants, 4-5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05-2·92) unadjusted and 1·67 (1·34-2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60-2·01) when unadjusted and 1·63 (1·41-1·91) when adjusted (p<0·0001 for all). The predictive accuracy of the optimised COV50 thresholds was 74·4% (71·6-77·1%) for mortality (threshold 0·47) and 67·4% (64·4-70·3%) for disease progression (threshold 0·04). When adjusted for covariables and the baseline WHO score, these thresholds improved AUCs from 0·835 to 0·853 (p=0·033) for death and from 0·697 to 0·730 (p=0·0008) for progression. Of 196 participants who received ambulatory care, 194 (99%) did not reach the 0·04 threshold. The cost reductions associated with 1 day less hospitalisation per 1000 participants were million Euro (M€) 0·887 (5-95% percentile interval 0·730-1·039) in participants at a low risk (COV50 <0·04) and M€2·098 (1·839-2·365) in participants at a high risk (COV50 ≥0·04). INTERPRETATION: The urinary proteomic COV50 marker might be predictive of adverse COVID-19 outcomes. Even in people with mild-to-moderate PCR-confirmed infections (WHO scores 1-4), the 0·04 COV50 threshold justifies earlier drug treatment, thereby potentially reducing the number of days in hospital and associated costs. FUNDING: German Federal Ministry of Health.

Optimized Self-Adaptive Power Distribution for Microgrids in a Typical Tourism Water Village of Northern China under COVID-19 Background

This work presents an improved self-adaptive power distribution approach for the microgrid in five modes under different pandemic conditions in a typical tourism water village in Northern China. Differently from the other studies, this work concentrates on satisfying the specific power supply requirements under the COVID-19 background, with the maximum value of the composite index as the object function. Composite index includes not only the economic factors, but also some compulsive factors to ensure the requested power supply of the residents/tourists. The improved particle swarm optimization method which employs the modified weighted factor and the elite strategy is utilized to optimize the power dispatching of the microgrid. Moreover, the impact of the pandemic has been fully considered by comparing the power dispatching before and after the pandemic. The case study in Baiyangdian Region confirms the effectiveness of the proposed method. With this method, the optimal power dispatching is determined under different modes.

Application of Visitor Eye Movement Information to Museum Exhibit Analysis

The motivation of this study is that after the COVID-19 epidemic, museum exhibition visits have also been significantly affected. The purpose of this research is to better understand the visual cognition of visitors, so as to improve the application of physical field or online exhibitions. Currently, no research is available on the differences in the visitor's viewing and cognitive process with eye movements sequence analysis that stem from the exhibition planning and design of different museums. This study tracks and analyzes the eye movement trajectories of visitors and studies its relation to learning and cognition and finds the key to influencing cognition through behavioral sequence analysis of displayed content. The results show that those interested in the displayed content have better cognitive performance, are immersed in reading text, and have a substantial shift in eye movement. Contrarily, those not interested in the displayed content are distracted and often turn their attention back to the title of the content. In this study, eye movement and fixation are indicators that can be used as a reference for the future design of displays to improve the effectiveness of presenting information to a visitor. Furthermore, this research can also provide future applications in integrating the virtual world and cognitive information, in the application of AR, VR, or metaverse environment, to provide people's cognition of rapid information in the virtual environment.

A recombinant infectious bronchitis virus from a chicken with a spike gene closely related to that of a turkey coronavirus

Using viral metagenomics, the complete genome sequence of an infectious bronchitis virus (IBV) strain (named ahysx-1) from a fecal sample from a healthy chicken in Anhui province, China, was determined. The genome sequence of ahysx-1 was found to be very similar to that of IBV strain ck/CH/LLN/131040 (KX252787), except for the spike gene region, which is similar to that of a turkey coronavirus strain (EU022526), suggesting that ahysx-1 is a recombinant. Recombination analysis and phylogenetic analysis based on the genomic sequences of ahysx-1 and other related strains confirmed that ahysx-1 appears to be a recombinant resulting from a recombination event that occurred between a chicken coronavirus and a turkey coronavirus. Further studies need to be performed to determine whether this recombinant IBV strain is pathogenic and whether it is transmitted between chickens and turkeys.

Low-Dose SARS-CoV-2 S-Trimer with an Emulsion Adjuvant Induced Th1-Biased Protective Immunity.

During the sustained COVID-19 pandemic, global mass vaccination to achieve herd immunity can prevent further viral spread and mutation. A protein subunit vaccine that is safe, effective, stable, has few storage restrictions, and involves a liable manufacturing process would be advantageous to distribute around the world. Here, we designed and produced a recombinant spike (S)-Trimer that is maintained in a prefusion state and exhibits a high ACE2 binding affinity. Rodents received different doses of S-Trimer (0.5, 5, or 20 µg) antigen formulated with aluminum hydroxide (Alum) or an emulsion-type adjuvant (SWE), or no adjuvant. After two vaccinations, the antibody response, T-cell responses, and number of follicular helper T-cells (Tfh) or germinal center (GC) B cells were assessed in mice; the protective efficacy was evaluated on a Syrian hamster infection model. The mouse studies demonstrated that adjuvating the S-Trimer with SWE induced a potent humoral immune response and Th1-biased cellular immune responses (in low dose) that were superior to those induced by Alum. In the Syrian hamster studies, when S-Trimer was adjuvanted with SWE, higher levels of neutralizing antibodies were induced against live SARS-CoV-2 from the original lineage and against the emergence of variants (Beta or Delta) with a slightly decreased potency. In addition, the SWE adjuvant demonstrated a dose-sparing effect; thus, a lower dose of S-Trimer as an antigen (0.5 µg) can induce comparable antisera and provide complete protection from viral infection. These data support the utility of SWE as an adjuvant to enhance the immunogenicity of the S-Trimer vaccine, which is feasible for further clinical testing.