COVID-19 Vaccine Hesitancy Among Patients Recovered From COVID-19 Infection in Wuhan, China: Cross-Sectional Questionnaire Study.

BACKGROUND: Although patients recovered from COVID-19 already have immunity gained from natural infection, they are still at risk of reinfection due to the emergence of new variants of COVID-19 and the diminishing of naturally acquired immunity over time. Vaccination is associated with efficacious protection against COVID-19 infection and could boost infection-acquired immunity; however, various COVID-19 survivors have not been vaccinated due to vaccine hesitancy. OBJECTIVE: The aim of this study was to investigate COVID-19 vaccine hesitancy and related factors among COVID-19 survivors. METHODS: A cross-sectional questionnaire survey was conducted among patients who recovered from COVID-19 infection in Wuhan, China, between June 10 and July 25, 2021. The questionnaire included sociodemographic information, items on COVID-19 infection, the COVID-19 vaccine hesitancy scale based on the 3Cs (complacency, convenience, and confidence) model, trust in vaccine manufacturers and health facilities, and reasons for the decision to accept COVID-19 vaccination. Multivariate logistic regression analysis was used to assess the factors influencing COVID-19 vaccine hesitancy. RESULTS: Among the 1422 participants, 538 (37.8%) were not vaccinated against COVID-19. The COVID-19-recovered patients who self-reported having a current unhealthy status expressed more hesitancy about the COVID-19 vaccine than those who perceived themselves to be healthy (odds ratio [OR] 0.45, 95% CI 0.28-0.71). Compared to the asymptomatic patients, patients with mild symptoms were more likely to receive a COVID-19 vaccine (OR 1.67, 95% CI 1.02-2.82). Regarding the 3Cs model, high complacency (P=.005) and low convenience (P=.004) were significant negative factors for COVID-19 vaccination. Trust in vaccine manufacturers and health facilities was a significant positive factor for COVID-19 vaccination (OR 1.14, 95% CI 1.09-1.19). "Self-needs" was the main reason for patients to receive the COVID-19 vaccine, whereas "already have antibodies and do not need vaccination" was the main reason for patients to not receive the COVID-19 vaccine. CONCLUSIONS: Among the three major factors of vaccine hesitancy, complacency proved to be the most notable among COVID-19-recovered patients. Therefore, educational campaigns can focus on raising the awareness of risk of infection and the benefits of vaccination to reduce complacency toward vaccination among this population. In particular, for individuals who have recovered from COVID-19, improving factors related to convenience such as transportation, the environment of vaccination, and providing door-to-door service was also deemed necessary to facilitate their vaccination. In addition, addressing the concerns about vaccination of COVID-19-recovered patients could foster trust and promote their uptake of vaccination.

Mpox multi-antigen mRNA vaccine candidates by a simplified manufacturing strategy afford efficient protection against lethal orthopoxvirus challenge.

Current unprecedented mpox outbreaks in non-endemic regions represent a global public health concern. Although two live-attenuated vaccinia virus (VACV)-based vaccines have been urgently approved for people at high risk for mpox, a safer and more effective vaccine that can be available for the general public is desperately needed. By utilizing a simplified manufacturing strategy of mixing DNA plasmids before transcription, we developed two multi-antigen mRNA vaccine candidates, which encode four (M1, A29, B6, A35, termed as Rmix4) or six (M1, H3, A29, E8, B6, A35, termed as Rmix6) mpox virus antigens. We demonstrated that those mpox multi-antigen mRNA vaccine candidates elicited similar potent cross-neutralizing immune responses against VACV, and compared to Rmix4, Rmix6 elicited significantly stronger cellular immune responses. Moreover, immunization with both vaccine candidates protected mice from the lethal VACV challenge. Investigation of B-cell receptor (BCR) repertoire elicited by mpox individual antigen demonstrated that the M1 antigen efficiently induced neutralizing antibody responses, and all neutralizing antibodies among the top 20 frequent antibodies appeared to target the same conformational epitope as 7D11, revealing potential vulnerability to viral immune evasion. Our findings suggest that Rmix4 and Rmix6 from a simplified manufacturing process are promising candidates to combat mpox.

Vaccine hesitancy promotes emergence of new SARS-CoV-2 variants.

The successive emergence of SARS-CoV-2 mutations has led to an unprecedented increase in COVID-19 incidence worldwide. Currently, vaccination is considered to be the best available solution to control the ongoing COVID-19 pandemic. However, public opposition to vaccination persists in many countries, which can lead to increased COVID-19 caseloads and hence greater opportunities for vaccine-evasive mutant strains to arise. To determine the extent that public opinion regarding vaccination can induce or hamper the emergence of new variants, we develop a model that couples a compartmental disease transmission framework featuring two strains of SARS-CoV-2 with game theoretical dynamics on whether or not to vaccinate. We combine semi-stochastic and deterministic simulations to explore the effect of mutation probability, perceived cost of receiving vaccines, and perceived risks of infection on the emergence and spread of mutant SARS-CoV-2 strains. We find that decreasing the perceived costs of being vaccinated and increasing the perceived risks of infection (that is, decreasing vaccine hesitation) will decrease the possibility of vaccine-resistant mutant strains becoming established by about fourfold for intermediate mutation rates. Conversely, we find increasing vaccine hesitation to cause both higher probability of mutant strains emerging and more wild-type cases after the mutant strain has appeared. We also find that once a new variant has emerged, perceived risk of being infected by the original variant plays a much larger role than perceptions of the new variant in determining future outbreak characteristics. Furthermore, we find that rapid vaccination under non-pharmaceutical interventions is a highly effective strategy for preventing new variant emergence, due to interaction effects between non-pharmaceutical interventions and public support for vaccination. Our findings indicate that policies that combine combating vaccine-related misinformation with non-pharmaceutical interventions (such as reducing social contact) will be the most effective for avoiding the establishment of harmful new variants.

Safety, immunogenicity, and efficacy of the mRNA vaccine CS-2034 as a heterologous booster versus homologous booster with BBIBP-CorV in adults aged ≥18 years: a randomised, double-blind, phase 2b trial.

BACKGROUND: Heterologous boosting is suggested to be of use in populations who have received inactivated COVID-19 vaccines. We aimed to assess the safety and immunogenicity of a heterologous vaccination with the mRNA vaccine CS-2034 versus the inactivated BBIBP-CorV as a fourth dose, as well as the efficacy against the SARS-CoV-2 omicron (BA.5) variant. METHODS: This trial contains a randomised, double-blind, parallel-controlled study in healthy participants aged 18 years or older (group A) and an open-label cohort in participants 60 years and older (group B), who had received three doses of inactivated whole-virion vaccines at least 6 months before enrolment. Pregnant women and people with major chronic illnesses or a history of allergies were excluded. Eligible participants in group A were stratified by age (18-59 years and ≥60 years) and then randomised by SAS 9.4 in a ratio of 3:1 to receive a dose of the mRNA vaccine (CS-2034, CanSino, Shanghai, China) or inactivated vaccine (BBIBP-CorV, Sinopharm, Beijing, China). Safety and immunogenicity against omicron variants of the fourth dose were evaluated in group A. Participants 60 years and older were involved in group B for safety observations. The primary outcome was geometric mean titres (GMTs) of the neutralising antibodies against omicron and seroconversion rates against BA.5 variant 28 days after the boosting, and incidence of adverse reactions within 28 days. The intention-to-treat group was involved in the safety analysis, while all patients in group A who had blood samples taken before and after the booster were involved in the immunogenicity analysis. This trial was registered at the Chinese Clinical Trial Registry Centre (ChiCTR2200064575). FINDINGS: Between Oct 13, and Nov 22, 2022, 320 participants were enrolled in group A (240 in the CS-2034 group and 80 in the BBIBP-CorV group) and 113 in group B. Adverse reactions after vaccination were more frequent in CS-2034 recipients (158 [44·8%]) than BBIBP-CorV recipients (17 [21·3%], p<0·0001). However, most adverse reactions were mild or moderate, with grade 3 adverse reactions only reported by eight (2%) of 353 participants receiving CS-2034. Heterologous boosting with CS-2034 elicited 14·4-fold (GMT 229·3, 95% CI 202·7-259·4 vs 15·9, 13·1-19·4) higher concentration of neutralising antibodies to SARS-CoV-2 omicron variant BA.5 than did homologous boosting with BBIBP-CorV. The seroconversion rates of SARS-CoV-2-specific neutralising antibody responses were much higher in the mRNA heterologous booster regimen compared with BBIBP-CorV homologous booster regimen (original strain 47 [100%] of 47 vs three [18·8%] of 16; BA.1 45 [95·8%] of 48 vs two [12·5%] 16; and BA.5 233 [98·3%] of 240 vs 15 [18·8%] of 80 by day 28). INTERPRETATION: Both the administration of mRNA vaccine CS-2034 and inactivated vaccine BBIBP-CorV as a fourth dose were well tolerated. Heterologous boosting with mRNA vaccine CS-2034 induced higher immune responses and protection against symptomatic SARS-CoV-2 omicron infections compared with homologous boosting, which could support the emergency use authorisation of CS-2034 in adults. FUNDING: Science and Technology Commission of Shanghai, National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Hematological characteristics of COVID-19 patients with fever infected by the Omicron variant in Shanghai: A retrospective cohort study in China.

BACKGROUND: A wave of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly spread in Shanghai, China. Hematological abnormalities have been reported in coronavirus disease 2019 (COVID-19) patients; however, the difference in hematological parameters between COVID-19 patients with fever and patients who are febrile from other causes remains unexplored. METHODS: This retrospective cohort study enrolled 663 SARS-CoV-2 positive patients identified by RT-PCR. Clinical parameters, including age, sex, and threshold cycle values of all COVID-19 patients, and hematological parameters of COVID-19 patients in the fever clinic were abstracted for analysis. RESULTS: Overall, 60.8% of COVID-19 patients were male, and the median age was 45 years. Most of COVID-19 patients were asymptomatic, while 25.8% of patients showed fever and 10.9% of patients had other emergencies. COVID-19 patients with fever had significantly lower white blood cells (WBCs), neutrophils, lymphocytes, platelets and C-reactive protein (CRP), and significantly higher monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and mean platelet volume-to-platelet ratio (MPR) levels, compared with those in SARS-CoV-2 negative patients with fever from other causes (p < 0.05). Neutrophil-to-lymphocyte ratio (NLR), PLR, and systemic inflammatory index (SII) levels were significantly higher in COVID-19 patients with emergencies (p < 0.05). WBCs showed the best performance with an area under the curve (0.756), followed by neutrophils (0.730) and lymphocytes (0.694) in the diagnosis of COVID-19 in the fever clinic. CONCLUSION: WBCs, neutrophils, lymphocytes, platelets, CRP and MLR, PLR, and MPR may be useful in early diagnosis of COVID-19 in the fever clinic.

Lessons drawn from Shanghai for controlling highly transmissible SARS-CoV-2 variants: insights from a modelling study.

BACKGROUND: The continuous emergence of novel SARS-CoV-2 variants with markedly increased transmissibility presents major challenges to the zero-COVID policy in China. It is critical to adjust aspects of the policy about non-pharmaceutical interventions (NPIs) by searching for and implementing more effective ways. We use a mathematical model to mimic the epidemic pattern of the Omicron variant in Shanghai to quantitatively show the control challenges and investigate the feasibility of different control patterns in avoiding other epidemic waves. METHODS: We initially construct a dynamic model with a core step-by-step release strategy to reveal its role in controlling the spread of COVID-19, including the city-based pattern and the district-based pattern. We used the least squares method and real reported case data to fit the model for Shanghai and its 16 districts, respectively. Optimal control theory was utilized to explore the quantitative and optimal solutions of the time-varying control strength (i.e., contact rate) to suppress the highly transmissible SARS-CoV-2 variants. RESULTS: The necessary period for reaching the zero-COVID goal can be nearly 4 months, and the final epidemic size was 629,625 (95%CI: [608,049, 651,201]). By adopting the city-based pattern, 7 out of 16 strategies released the NPIs more or earlier than the baseline and ensured a zero-resurgence risk at the average cost of 10 to 129 more cases in June. By adopting the district-based pattern, a regional linked release can allow resumption of social activity to ~ 100% in the boundary-region group about 14 days earlier and allow people to flow between different districts without causing infection resurgence. Optimal solutions of the contact rate were obtained with various testing intensities, and higher diagnosis rate correlated with higher optimal contact rate while the number of daily reported cases remained almost unchanged. CONCLUSIONS: Shanghai could have been bolder and more flexible in unleashing social activity than they did. The boundary-region group should be relaxed earlier and more attention should be paid to the centre-region group. With a more intensive testing strategy, people could return to normal life as much as possible but still ensure the epidemic was maintained at a relatively low level.

Suicidal ideation and associated risk factors among COVID-19 patients who recovered from the first wave of the pandemic in Wuhan, China.

BACKGROUND/OBJECTIVES: Symptoms of psychiatric, neurological, and physical illnesses with post-COVID syndrome could increase suicidal ideation (SI) and behavior in COVID-19 survivors. However, information on the level of SI among COVID-19 survivors in China is still limited. We aimed to assess the prevalence and risk factors of SI among COVID-19 survivors in Wuhan, China. METHODS: The cross-sectional study was carried out among former COVID-19 patients in Jianghan District (Wuhan, China) from June 10 to July 25, 2021. SI, fatigue, stigma, sleep disorder, resilience, peace of mind, and social support of the participants were measured by the SI-related item, Fatigue Scale (FS-14), short version of COVID-19 Stigma Scale, Pittsburgh Sleep Quality Index (PSQI), The Peace of Mind Scale (PoM), The Resilience Style Questionnaire (RSQ) and two single separate items for measuring social support. Logistic regression was utilized to identify associated factors of SI. Mediation analysis was performed to assess the potential mechanisms between psychological factors and SI. RESULTS: A total of 1,297 participants were included in this study. 6.7% of them reported SI. Marriage (AOR = 0.389, P = 0.003) and peace of mind (AOR = 0.854, P < 0.001) were negatively associated with SI. History of psychological or emotional counseling before COVID-19 infection (AOR = 1.889, P = 0.049), fatigue (AOR = 1.110, P = 0.007), higher self-reported COVID-19 related stigma (AOR = 1.054, P = 0.003) and sleep disorder (AOR = 1.112, P = 0.001) were positively associated with SI. CONCLUSIONS: Consideration should be taken into account to develop appropriate alleviating measures such as mindfulness-based cognitive therapy to reduce the rates of SI among COVID-19 survivors and improve their resilience to cope with the personal impact of the COVID-19 pandemic.

Entangling of Peptide Nanofibers Reduces the Invasiveness of SARS-CoV-2.

The viral spike (S) protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells, facilitating its entry and infection. Here, functionalized nanofibers targeting the S protein with peptide sequences of IRQFFKK, WVHFYHK and NSGGSVH, which are screened from a high-throughput one-bead one-compound screening strategy, are designed and prepared. The flexible nanofibers support multiple binding sites and efficiently entangle SARS-CoV-2, forming a nanofibrous network that blocks the interaction between the S protein of SARS-CoV-2 and the ACE2 on host cells, and efficiently reduce the invasiveness of SARS-CoV-2. In summary, nanofibers entangling represents a smart nanomedicine for the prevention of SARS-CoV-2.

An ACAT inhibitor suppresses SARS-CoV-2 replication and boosts antiviral T cell activity.

The severity of disease following infection with SARS-CoV-2 is determined by viral replication kinetics and host immunity, with early T cell responses and/or suppression of viraemia driving a favourable outcome. Recent studies uncovered a role for cholesterol metabolism in the SARS-CoV-2 life cycle and in T cell function. Here we show that blockade of the enzyme Acyl-CoA:cholesterol acyltransferase (ACAT) with Avasimibe inhibits SARS-CoV-2 pseudoparticle infection and disrupts the association of ACE2 and GM1 lipid rafts on the cell membrane, perturbing viral attachment. Imaging SARS-CoV-2 RNAs at the single cell level using a viral replicon model identifies the capacity of Avasimibe to limit the establishment of replication complexes required for RNA replication. Genetic studies to transiently silence or overexpress ACAT isoforms confirmed a role for ACAT in SARS-CoV-2 infection. Furthermore, Avasimibe boosts the expansion of functional SARS-CoV-2-specific T cells from the blood of patients sampled during the acute phase of infection. Thus, re-purposing of ACAT inhibitors provides a compelling therapeutic strategy for the treatment of COVID-19 to achieve both antiviral and immunomodulatory effects. Trial registration: NCT04318314.

Perceptive movement of susceptible individuals with memory.

The perception of susceptible individuals naturally lowers the transmission probability of an infectious disease but has been often ignored. In this paper, we formulate and analyze a diffusive SIS epidemic model with memory-based perceptive movement, where the perceptive movement describes a strategy for susceptible individuals to escape from infections. We prove the global existence and boundedness of a classical solution in an n-dimensional bounded smooth domain. We show the threshold-type dynamics in terms of the basic reproduction number [Formula: see text]: when [Formula: see text], the unique disease-free equilibrium is globally asymptotically stable; when [Formula: see text], there is a unique constant endemic equilibrium, and the model is uniformly persistent. Numerical analysis exhibits that when [Formula: see text], solutions converge to the endemic equilibrium for slow memory-based movement and they converge to a stable periodic solution when memory-based movement is fast. Our results imply that the memory-based movement cannot determine the extinction or persistence of infectious disease, but it can change the persistence manner.

Estimating the time-dependent effective reproduction number and vaccination rate for COVID-19 in the USA and India.

The effective reproduction number, $ R_t $, is a vital epidemic parameter utilized to judge whether an epidemic is shrinking, growing, or holding steady. The main goal of this paper is to estimate the combined $ R_t $ and time-dependent vaccination rate for COVID-19 in the USA and India after the vaccination campaign started. Accounting for the impact of vaccination into a discrete-time stochastic augmented SVEIR (Susceptible-Vaccinated-Exposed-Infectious-Recovered) model, we estimate the time-dependent effective reproduction number $ (R_t) $ and vaccination rate $ (\xi_t) $ for COVID-19 by using a low pass filter and the Extended Kalman Filter (EKF) approach for the period February 15, 2021 to August 22, 2022 in India and December 13, 2020 to August 16, 2022 in the USA. The estimated $ R_t $ and $ \xi_t $ show spikes and serrations with the data. Our forecasting scenario represents the situation by December 31, 2022 that the new daily cases and deaths are decreasing for the USA and India. We also noticed that for the current vaccination rate, $ R_t $ would remain greater than one by December 31, 2022. Our results are beneficial for the policymakers to track the status of the effective reproduction number, whether it is greater or less than one. As restrictions in these countries ease, it is still important to maintain safety and preventive measures.

The role of high cholesterol in SARS-CoV-2 infectivity

Coronavirus disease 2019 (COVID19) is a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus binds to angiotensinogen converting enzyme 2 (ACE2) which mediates viral entry into mammalian cells. COVID19 is notably severe in elderly and those with underlying chronic conditions. The cause of selective severity is not well understood. Here we show cholesterol and the signaling lipid phosphatidyl-inositol 4,5 bisphosphate (PIP2) regulate viral infectivity through the localization of ACE2's into nanoscopic (<200 nm) lipid clusters. Uptake of cholesterol into cell membranes (a condition common to chronic disease) causes ACE2 to move from PIP2 lipids to endocytic ganglioside (GM1) lipids, where the virus is optimally located for viral entry. In mice, age, and high fat diet increase lung tissue cholesterol by up to 40%. And in smokers with chronic disease, cholesterol is elevated two-fold, a magnitude of change that dramatically increases infectivity of virus in cell culture. We conclude increasing the ACE2 location near endocytic lipids increases viral infectivity and may help explain the selective severity of COVID-19 in aged and diseased populations.

Proxalutamide for the treatment of COVID-19 rebound following Paxlovid treatment: Report of four cases and review of the literature.

BACKGROUND: The pandemic the coronavirus disease 2019 (COVID-19) has created a global health crisis. Although Paxlovid is recommended for the early-stage treatment of mild-to-moderate COVID-19 in patients at increased risk of progression to severe COVID-19, more and more cases are reported a COVID-19 rebound after Paxlovid treatment. Currently, information on the additional treatment for COVID-19 rebound following Paxlovid treatment is limited. CASE REPORT: Here, we present four cases with COVID-19 who were mild on admission. All cases experienced a COVID-19 rebound and progressed to severe COVID-19, following treatment with Paxlovid (300 mg of nirmatrelvir with 100 mg ritonavir, twice daily for 5 days). After being treated with proxalutamide (300 mg/day), all cases finally turned real-time reverse transcription polymerase chain reaction (RT-PCR) negative. CONCLUSION: Our cases suggested that proxalutamide might be an effective remedial treatment option for patients experiencing a COVID-19 rebound after Paxlovid treatment.

Perceived stigma among discharged patients of COVID-19 in Wuhan, China: A latent profile analysis.

Background: Perceived stigma has greatly influenced the life quality of the COVID-19 patients who recovered and were discharged (RD hereafter). It is essential to understand COVID-19 stigma of RD and its related risk factors. The current study aims to identify the characteristics of perceived COVID-19 stigma in RD using latent profile analysis (LPA), to explore its psycho-social influencing factors, and to determine the cut-off point of the stigma scale using receiver operating characteristic (ROC) analysis. Methods: A cross-sectional study was conducted among COVID-19 RD in 13 communities in Jianghan District, Wuhan City, Hubei Province, China from June 10 to July 25, 2021, enrolling total 1,297 participants. Data were collected on demographic characteristics, COVID-19 perceived stigma, post-traumatic stress disorder (PTSD), anxiety, depression, sleep disorder, fatigue, resilience, social support, and peace of mind. LPA was performed to identify different profiles of perceived COVID-19 stigma level. Univariate analysis and multinominal logistic regression analysis were conducted to explore the influencing factors in different profiles. ROC analyses was carried out to identify the cut-off value of perceived stigma. Results: Among the participants, three profiles of perceived stigma were identified: "low perceived COVID-19 stigma" (12.8%), "moderate perceived COVID-19 stigma" (51.1%), and "severe perceived COVID-19 stigma" (36.1%). Multinominal logistic regression analysis revealed that older age, living with other people, anxiety, and sleep disorder were positively associated with moderate perceived COVID-19 stigma, while higher educational level was negatively associated with moderate perceived COVID-19 stigma. Female, older age, living with other people, anxiety, and sleep disorder were positively associated with severe perceived COVID-19 stigma, while higher educational level, social support, and peace of mind were negatively associated with severe perceived COVID-19 stigma. ROC curve of the Short Version of COVID-19 Stigma Scale (CSS-S) for screening perceived COVID-19 stigma showed that the optimal cut-off value was ≥ 20. Conclusion: The study focuses on the issue of perceived COVID-19 stigma and its psycho-socio influencing factors. It provides evidence for implementing relevant psychological interventions to COVID-19 RD.

Increase in body mass index during the COVID-19 pandemic among people who smoke: An analysis of multi-site electronic health records.

The effects of the COVID-19 period among people who smoke (compared by sex) are largely unknown. The purpose of this study was to compare body mass index (BMI) increase among men and women who smoked during the pandemic. We used a retrospective longitudinal, observational study design of secondary data. We used electronic health records from TriNetX network (n = 486,072) from April 13, 2020-May 5, 2022 among adults aged 18-64 who smoked and had a normal BMI prior to the pandemic. The main measure was a change of BMI from < 25 to ≥25. Risk ratio was determined between men and women with propensity score matching. Overall, 15.8% increased BMI to ≥25; 44,540 (18.3%) were women and 32,341 (13.3%) were men (Risk Ratio = 1.38, 95% CI: 1.36, 1.40; p < .0001). Adults with diabetes, hypertension, asthma, COPD or emphysema or who were women, were more likely to develop BMI≥25 during the pandemic. Women who smoked were more likely to have an increase in BMI than men who smoked during the COVID-19 period.

Patients with advanced pancreatic and biliary cancer appear vulnerable to SARS-CoV-2 Omicron variant: An observational study during the COVID-19 outbreak in Shanghai.

Background: The COVID-19 pandemic has spread rapidly across the globe. Cancer patients have a higher risk of severe infections and associated mortality than the general population. However, the lethal effect of Omicron-variant affection on advanced pancreatic and biliary cancer patients is still not clear. Herein, we designed an observational study to shed light on the influence of the Omicron variant on this so-called "King of Cancer" and improve management of these patients with COVID-19 in the future. Methods: Omicron-infected patients with advanced pancreatic and biliary cancer were enrolled from 15 April to 31 May 2022. Four groups were set up in this study: Group 1, Omicron-infected cancer patients (N = 4); Group 2, non-infected cancer patients (N = 4); Group 3, infected non-cancer-afflicted subjects (N = 4); Group 4, non-infected non-cancer-afflicted subjects (N = 4). On Days 0, 7, and 14 after infection, the blood samples were collected dynamically from all subjects. The primary endpoints were disease severity and survival. Results: At the endpoint of this observational study, Patient Nos. 2, 3, and 4 died separately on Days 11, 25, and 13 after viral infection. All of them had advanced cancer, with a death rate of up to 75%. Group 1 presented an overall T-cell exhaustion status compared with other groups. Group 1 had obviously lower T-cell populations and higher B-cell percentages and CD4+T/CD8+T ratios (P <0.05). Time-course cytokine monitoring results showed that IL-1ß was significantly decreased in Group 1 (P <0.05) and generally kept at a low level without obvious fluctuation. IL-6 was markedly increased in infected cancer patients (P <0.01) but remained at a low level and had no apparent change during the whole infection process in non-cancer-afflicted subjects. Furthermore, several inflammatory parameter indexes indicated a tight association of Omicron infection with the disease course and prognosis of Omicron-infected cancer patients. Conclusions: Advanced pancreatic and biliary cancer patients with Omicron infection have severe symptoms and poor outcomes. More attention, protective measures, and routine healthcare services should be recommended to these vulnerable populations in clinical practice during the pandemic in the foreseeable future.

Developing and testing a protocol to systematically assess social interaction with urban outdoor environment.

Social interaction is significant for individuals' mental and psychological well-being in communities. With the growing demand for outdoor activities in urban settings under the COVID­19 pandemic, urban parks have become important public resources for human social activities. Researchers have developed numerous instruments to measure park use behaviors, but most are designed for assessing physical activity while ignoring social interactive behaviors. Despite the importance, no single protocol objectively assesses the range of social interactions in urban outdoor environments. To bridge the research gap, we have developed a social interaction scale (SIS) based on Parten's scheme. The innovative protocol, named Systematically Observing Social Interaction in Parks (SOSIP) was developed based on the SIS, allowing systematic evaluation of human's interactive behaviors in outdoor environment both from their levels of social interaction and group size. The psychometric properties of SOSIP were established through the verification of content validity and reliability tests. Additionally, we applied SOSIP to explore relationships between park features and social interaction via hierarchical linear models (HLMs). Statistical comparisons between SOSIP and other forms of social interaction were discussed and indicated strong reliability of applying SOSIP. The results indicated SOSIP is a valid and reliable protocol for objectively assessing social interactive behaviors within urban outdoor environments and informing better understanding of individuals' mental and psychological health benefits.

The personalized recommendation for OTA flight cancellation and change services during the pandemic

The COVID-19 pandemic has had a dramatic impact on people's travels. Due to the recurrent pandemic and regionally different policies in China, travelers must pay a lot for flight cancellations and changes. To accommodate this, online travel agencies (OTA) can provide a more flexible ancillary as a supplement to the airline company's services. Here, we introduced the upgraded all-in-one (AIO) service package, which offers compensation for flight delays, changes, or refund. We also designed a dynamic recommendation engine (DRE), which can make real-time personalized recommendations. Backed by AB testing, the machine learning-based DRE not only raises the package attach rate without interrupting the flight ordering process, but also helps the customers cut cost when making flight cancellations or changes.

Mediating effect of perceived social support between mindfulness level and mental health of nursing undergraduates during the epidemic of novel coronavirus pneumonia

Objective: To study students' mental health status during epidemic of novel coronavirus pneumonia, and to explore the influence of mindfulness level and perceived social support on mental health. Methods: A total of 240 undergraduate nursing students were investigated with Depression Anxiety and Stress Scale, Five Facets Mindfulness Questionnaire, Perceived Social Support Scale and Pittsburgh Sleep Quality Index. SAS and Mplus were applied to describe the data and conduct mediation analysis. Results: About 18.8% of the participants were depressed and 27.9% were anxious, 13.3% were stressed, and 31.7% had problems of sleeping. The mindfulness level could directly affect sleep disorder (beta = - 0.242, P < 0.001), stress (beta = - 0.397, P < 0.001), anxiety (beta = - 0.350, P < 0.001)and depression(beta = - 0.484, P < 0.001), and could also indirectly affect sleep disorder (beta = - 0.171, P < 0.001), stress (beta = - 0.105, P = 0.029), anxiety (beta = - 0.102, P = 0.034) and depression (beta = - 0.180, P < 0.001) via the mediation role of perceived social support with the mediating effects accounted for 41.40%, 20.92%, 22.52% and 37.19%, respectively. Conclusions: Mindfulness level can improve the mental health of nursing undergraduates through direct action and understanding the intermediary role of social support. Nursing educators can consider integrating mindfulness decompression training into daily teaching, and give nursing undergraduates enough psychological and emotional support and encouragement to improve their mental health level.

The SAR-based development of small molecular HBV capsid assembly modulators

Hepatitis B virus (HBV) infected about 296 million people worldwidely, while clinical useful therapeutic agents were still limited. Capsid assembly modulators (CAM) have been validated as efficient anti-HBV virus agents with the potential to achieve functional cure, therefore piqued much attention in recent years. There are various novel scaffold agents been developed and more than ten CAM candidates have been progressed into clinical trials with efficient anti-HBV activities. Herein, we summarised the SAR-based development of CAMs with various scaffolds, including heteroaryldihydropyrimidines (HAPs), phenylacrylamides (PPAs), sulfamoylbenzamides (SBAs), pyridazinone, bis-heterocycle, arylformamides, aminothiazoles, and others, which may provide new suggestions for the further development of CAMs.