Stigma and health inequality experienced by ethnic minorities during the COVID-19 pandemic in a Chinese community: an implication to health policymakers.

Introduction: Ethnic minorities are considered one of the most vulnerable groups during the COVID-19 pandemic. However, the explanatory pathway of how their disadvantaged experiences during epidemics are related to the embedded and longstanding stigmas against them and how these embedded stigmas can affect their resilience in disease outbreaks are not well understood. This study investigated the experiences of ethnic minorities in the COVID-19 pandemic, and how their experiences were related to the embedded stigma toward them. Methods: This study adopted a qualitative approach, interviewed 25 individuals (13 women and 12 men) from ethnic minority groups residing in Hong Kong from August 2021 to February 2022 in a semi-structured format. Thematic analysis was conducted to analyze the data. Results: The participants were isolated and stereotyped as infectious during the COVID-19 pandemic at community and institutional levels. Their experiences did not occur suddenly during the pandemic but were embedded in the longstanding segregation and negative stereotypes toward ethnic minorities in different aspects of life before the pandemic. These negative stereotypes affected their resilience in living and coping with the pandemic. Conclusion: The participants' experiences during the COVID-19 pandemic were mostly disadvantageous and predominantly initiated by the mainstream stigmatization toward them by the local Chinese residents and government. Their disadvantaged experiences in the pandemic should be traced to the embedded social systems, imposing structural disparities for ethnic minorities when accessing social and medical resources during a pandemic. Because of the preexisting stigmatization and social seclusion of ethnic minorities in Hong Kong, the participants experienced health inequality, which stemmed from social inequality and the power differential between them and the Chinese locals. The disadvantaged situation of the participants negatively affected their resilience to the pandemic. To enable ethnic minorities better cope with future epidemics, merely providing assistance to them during an epidemic is barely adequate, but a more supportive and inclusive social system should be established for them in the long run.

A pattern-centered analysis of adolescents' concerns and hopes about future crises: Differences in ways of coping and personal adjustment.

INTRODUCTION: Many adolescents are concerned about global and future crises, such as the health of the planet or terrorism/safety. Yet, adolescents can also express hope about the future. Thus, asking adolescents about their concern and hope could yield subgroups with different ways of coping and personal adjustment. METHOD: Australian adolescents (N = 863; age 10-16) completed surveys to report their concern (worry and anger) and hope about the planet, safety, jobs, income, housing, and technology, as well as their active and avoidant coping, depression, and life satisfaction. RESULTS: Four distinct subgroups were identified using cluster analysis: Hopeful (low on concern and high on hope across all issues, 32%), Uninvolved (low in concern and hope; 26%), Concerned about the Planet (CP, 27%), and Concerned about Future Life (CFL, 15%). When compared (adjusting for age, sex, and COVID timing), the CP subgroup was highest in active coping (e.g., taking action) but moderate in personal adjustment. Hopeful had the most positive adjustment, whereas CFL had the poorest adjustment. Uninvolved were lowest in coping but moderate in adjustment. CONCLUSIONS: Findings suggest ways of coping and adjustment may not always align, in that CP is connected with more active coping but also some cost to personal adjustment, whereas Hopeful is associated with optimal adjustment but perhaps at the cost of active coping. In addition, although CFL adolescents emerged as the at-risk group, the low levels of hope and coping in Uninvolved adolescents raise the possibility that they are at risk of future problems.

Using knowledge of, attitude toward, and daily preventive practices for COVID-19 to predict the level of post-traumatic stress and vaccine acceptance among adults in Hong Kong.

Introduction: COVID-19 has been perceived as an event triggering a new type of post-traumatic stress (PTSD) that can live during and after the pandemic itself. However, it remains unclear whether such PTSD is partly related to people's knowledge of, attitude toward and daily behavioral practices (KAP) for COVID-19. Methods: Through a telephone survey, we collected responses from 3,011 adult Hong Kong residents. Then using the Catboost machine learning method, we examined whether KAP predicted the participant's PTSD level, vaccine acceptance and participation in voluntary testing. Results: Results suggested that having good preventative practices for, poor knowledge of, and negative attitude toward COVID-19 were associated with greater susceptibility to PTSD. Having a positive attitude and good compliance with preventative practices significantly predicted willingness to get vaccinated and participate in voluntary testing. Good knowledge of COVID-19 predicted engagement in testing but showed little association with vaccine acceptance. Discussion: To maintain good mental health and ongoing vaccine acceptance, it is important to foster people's sense of trust and belief in health professionals' and government's ability to control COVID-19, in addition to strengthening people's knowledge of and compliance with preventative measures.

Immunogenicity and Durability of Antibody Responses to Homologous and Heterologous Vaccinations with BNT162b2 and ChAdOx1 Vaccines for COVID-19.

During the COVID-19 pandemic, vaccines were developed based on various platform technologies and were approved for emergency use. However, the comparative analysis of immunogenicity and durability of vaccine-induced antibody responses depending on vaccine platforms or vaccination regimens has not been thoroughly examined for mRNA- or viral vector-based vaccines. In this study, we assessed spike-binding IgG levels and neutralizing capacity in 66 vaccinated individuals prime-boost immunized either by homologous (BNT162b2-BNT162b2 or ChAdOx1-ChAdOx1) or heterologous (ChAdOx1-BNT162b2) vaccination for six months after the first vaccination. Despite the discrepancy in intervals for the prime-boost vaccination regimen of different COVID-19 vaccines, we found stronger induction and relatively rapid waning of antibody responses by homologous vaccination of the mRNA vaccine, while weaker boost effect and stable maintenance of humoral immune responses were observed in the viral vector vaccine group over 6 months. Heterologous vaccination with ChAdOx1 and BNT162b2 resulted in an effective boost effect with the highest remaining antibody responses at six months post-primary vaccination.

Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19.

In the absence of drugs to treat or prevent COVID-19, drug repurposing can be a valuable strategy. Despite a substantial number of clinical trials, drug repurposing did not deliver on its promise. While success was observed with some repurposed drugs (e.g., remdesivir, dexamethasone, tocilizumab, baricitinib), others failed to show clinical efficacy. One reason is the lack of clear translational processes based on adequate preclinical profiling before clinical evaluation. Combined with limitations of existing in vitro and in vivo models, there is a need for a systematic approach to urgent antiviral drug development in the context of a global pandemic. We implemented a methodology to test repurposed and experimental drugs to generate robust preclinical evidence for further clinical development. This translational drug development platform comprises in vitro, ex vivo, and in vivo models of SARS-CoV-2, along with pharmacokinetic modeling and simulation approaches to evaluate exposure levels in plasma and target organs. Here, we provide examples of identified repurposed antiviral drugs tested within our multidisciplinary collaboration to highlight lessons learned in urgent antiviral drug development during the COVID-19 pandemic. Our data confirm the importance of assessing in vitro and in vivo potency in multiple assays to boost the translatability of pre-clinical data. The value of pharmacokinetic modeling and simulations for compound prioritization is also discussed. We advocate the need for a standardized translational drug development platform for mild-to-moderate COVID-19 to generate preclinical evidence in support of clinical trials. We propose clear prerequisites for progression of drug candidates for repurposing into clinical trials. Further research is needed to gain a deeper understanding of the scope and limitations of the presented translational drug development platform.

COVID-19 one year on: identification of at-risk groups for psychological trauma and poor health-protective behaviour using a telephone survey.

BACKGROUND: This study examined the profiles and correlates of psychological trauma, compliance with preventative measures, vaccine acceptance and participation in voluntary testing during the novel coronavirus disease 2019 (COVID-19) pandemic among the adult population in Hong Kong (n = 3,011). METHODS: Data were collected through a telephone survey between December 2020 and February 2021, using measures of psychological trauma, compliance with preventative measures, reading news reports on COVID-19, vaccine acceptance and willingness to participate in voluntary testing. RESULTS: The prevalence of possible post-traumatic stress disorder was found to be 12.4%. Respondents were generally compliant with routine preventative measures, and approximately half had accepted vaccination and voluntary testing. Participants who had lower levels of education, were unemployed or had no income showed greater psychological trauma symptoms, whereas female, older and more educated participants showed greater compliance with preventative measures. Participants who spent more time watching news reports of COVID-19 had greater psychological trauma, but also greater compliance. Participants who were male, older, had lower education levels or were married showed greater acceptance of vaccination and participation in voluntary testing. CONCLUSIONS: Socio-demographic factors affected both psychological trauma and engagement in health-protective measures at one year after the onset of the pandemic. The theoretical and practical implications of these findings are discussed.

The application of technology to improve cognition in older adults: A review and suggestions for future directions.

The rapidly increasing worldwide population of older adults, along with the increasing prevalence of cognitive impairment and dementia in this population, is a growing health-care problem. As such, advances in technology-based cognitive interventions and games are playing an increasingly key role in preserving and improving older adults' cognitive function, especially during the COVID-19 pandemic when opportunities for face-to-face activities or training are few. In this paper, we summarize from previous studies systematic reviews and meta-analyses on the various types of technology used in cognitive interventions (namely, computerized cognitive training, virtual-reality interventions and robot-assisted interventions) and the empirical evidence on the effects of these technologies on global and specific cognitive functions in healthy and clinical populations of older adults (e.g., older adults with mild cognitive impairment or dementia). We also describe older adults' perceptions, experiences and acceptance of these technologies. Finally, we discuss the limitations, challenges and future avenues of research in this field.

Perceptions of and hesitancy toward COVID-19 vaccination in older Chinese adults in Hong Kong: a qualitative study.

BACKGROUND: COVID-19 vaccination is recommended for older adults by the World Health Organization. However, by July 15, 2021, only 26% of individuals over 60 years old in Hong Kong had received a first dose of the vaccine. The health belief model and the theory of planned behavior have been used to understand the determinants for COVID-19 vaccination in past literature. However, vaccination determinants can be complex and involve social and cultural factors that cannot be explained by micro-individual factors alone; hence, the health belief model and the theory of planned behavior cannot provide a complete understanding of vaccine hesitancy. Few studies on the barriers to, hesitancy toward, and motivations for COVID-19 vaccination among older Chinese adults have been performed. The aim of this study is to fill this gap by conducting a comprehensive analysis of this subject using the critical medical anthropology framework, extending the health belief model and the theory of planned behavior in understanding vaccination determinants among the older adult population. METHODS: Between November 2020 and February 2021, 31 adults (24 women and 7 men) over the age of 65 took part in semi-structured, one-on-one interviews. The data we gathered were then analyzed through a phenomenological approach. RESULTS: Two major themes in the data were examined: barriers to vaccination and motivations for vaccination. The participants' perceptions of and hesitancy toward vaccination demonstrated a confluence of factors at the individual (trust, confidence, and social support networks), microsocial (stigma toward health care workers), intermediate-social (government), and macrosocial (cultural stereotypes, civic and collective responsibility, and economic considerations) levels according to the critical medical anthropology framework. CONCLUSIONS: The decision to receive a COVID-19 vaccination is a complex consideration for older adults of low socioeconomic status in Hong Kong. Using the critical medical anthropology framework, the decision-making experience is a reflection of the interaction of factors at different layers of social levels. The findings of this study extend the health belief model and the theory of planned behavior regarding the understanding of vaccination perceptions and relevant behaviors in an older adult population.

Immune Responses to the ChAdOx1 nCoV-19 and BNT162b2 Vaccines and to Natural Coronavirus Disease 2019 Infections Over a 3-Month Period.

BACKGROUND: There are limited data directly comparing immune responses to vaccines and to natural infections with coronavirus disease 2019 (COVID-19). This study assessed the immunogenicity of the BNT162b2 and ChAdOx1 nCoV-19 vaccines over a 3-month period and compared the immune responses with those to natural infections. METHOD: We enrolled healthcare workers who received BNT162b2 or ChAdOx1 nCoV-19 vaccines and patients with confirmed COVID-19 and then measured S1 immunoglobulin (Ig) G and neutralizing antibodies and T-cell responses. RESULTS: A total of 121 vaccinees and 26 patients with confirmed COVID-19 were analyzed. After the second dose, the BNT162b2 vaccine yielded S1 IgG antibody responses similar to those achieved with natural infections (mean IgG titer [standard deviation], 2241 [899] vs 2601 [5039]; P = .68) but significantly stronger than responses to the ChAdOx1 vaccine (174 [96]; P < .001). The neutralizing antibody titer generated by BNT162b2 was 6-fold higher than that generated by ChAdOx1 but lower than that by natural infection. T-cell responses persisted for 3 months with BNT162b2 and natural infection but decreased with ChAdOx1. CONCLUSIONS: Antibody responses after the second dose of BNT162b2 are higher than after the second dose of ChAdOx1 and like those occurring after natural infection. T-cell responses are maintained longer in BNT162b2 vaccinees than in ChAdOx1 vaccinees.

Correlation between Reactogenicity and Immunogenicity after the ChAdOx1 nCoV-19 and BNT162b2 mRNA Vaccination.

Correlation between vaccine reactogenicity and immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Thus, we investigated to determine whether the reactogenicity after coronavirus disease 2019 vaccination is associated with antibody (Ab) titers and T cell responses. This study was prospective cohort study done with 131 healthcare workers at tertiary center in Seoul, South Korea. The degrees of the local reactions after the 1st and 2nd doses of ChAdOx1 nCov-19 (ChAdOx1) vaccination were significantly associated with the S1-specific IgG Ab titers (p=0.003 and 0.01, respectively) and neutralizing Ab (p=0.04 and 0.10, respectively) in age- and sex-adjusted multivariate analysis, whereas those after the BNT162b2 vaccination did not show significant associations. T cell responses did not show significant associations with the degree of reactogenicity after the ChAdOx1 vaccination or the BNT162b2 vaccination. Thus, high degree of local reactogenicity after the ChAdOx1 vaccine may be used as an indicator of strong humoral immune responses against SARS-CoV-2.

Comparison of Antibody and T Cell Responses Induced by Single Doses of ChAdOx1 nCoV-19 and BNT162b2 Vaccines.

There are limited data directly comparing humoral and T cell responses to the ChAdOx1 nCoV-19 and BNT162b2 vaccines. We compared Ab and T cell responses after first doses of ChAdOx1 nCoV-19 vs. BNT162b2 vaccines. We enrolled healthcare workers who received ChAdOx1 nCoV-19 or BNT162b2 vaccine in Seoul, Korea. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S1 protein-specific IgG Abs (S1-IgG), neutralizing Abs (NT Abs), and SARS-CoV-2-specific T cell response were evaluated before vaccination and at 1-wk intervals for 3 wks after vaccination. A total of 76 persons, comprising 40 injected with the ChAdOx1 vaccine and 36 injected with the BNT162b2 vaccine, participated in this study. At 3 wks after vaccination, the mean levels (±SD) of S1-IgG and NT Abs in the BNT162b2 participants were significantly higher than in the ChAdOx1 participants (S1-IgG, 14.03±7.20 vs. 6.28±8.87, p<0.0001; NT Ab, 183.1±155.6 vs. 116.6±116.2, p=0.035), respectively. However, the mean values of the T cell responses in the 2 groups were comparable after 2 wks. The humoral immune response after the 1st dose of BNT162b2 developed faster and was stronger than after the 1st dose of ChAdOx1. However, the T cell responses to BNT162b2 and ChAdOx1 were similar.

A new high-content screening assay of the entire hepatitis B virus life cycle identifies novel antivirals.

BACKGROUND & AIMS: Chronic hepatitis B is an incurable disease. Addressing the unmet medical need for therapies has been hampered by a lack of suitable cell culture models to investigate the HBV life cycle in a single experimental setup. We sought to develop a platform suitable to investigate all aspects of the entire HBV life cycle. METHODS: HepG2-NTCPsec+ cells were inoculated with HBV. Supernatants of infected cells were transferred to naïve cells. Inhibition of infection was determined in primary and secondary infected cells by high-content imaging of viral and cellular factors. Novel antivirals were triaged in cells infected with cell culture- or patient-derived HBV and in stably virus replicating cells. HBV internalisation and target-based receptor binding assays were conducted. RESULTS: We developed an HBV platform, screened 2,102 drugs and bioactives, and identified 3 early and 38 late novel HBV life cycle inhibitors using infectious HBV genotype D. Two early inhibitors, pranlukast (EC50 4.3 µM; 50% cytotoxic concentration [CC50] >50 µM) and cytochalasin D (EC50 0.07 µM; CC50 >50 µM), and 2 late inhibitors, fludarabine (EC50 0.1 µM; CC50 13.4 µM) and dexmedetomidine (EC50 6.2 µM; CC50 >50 µM), were further investigated. Pranlukast inhibited HBV preS1 binding, whereas cytochalasin D prevented the internalisation of HBV. Fludarabine inhibited the secretion of HBV progeny DNA, whereas dexmedetomidine interfered with the infectivity of HBV progeny. Patient-derived HBV genotype C was efficiently inhibited by fludarabine (EC50 0.08 µM) and dexmedetomidine (EC50 8.7 µM). CONCLUSIONS: The newly developed high-content assay is suitable to screen large-scale drug libraries, enables monitoring of the entire HBV life cycle, and discriminates between inhibition of early and late viral life cycle events. LAY SUMMARY: HBV infection is an incurable, chronic disease with few available treatments. Addressing this unmet medical need has been hampered by a lack of suitable cell culture models to study the entire viral life cycle in a single experimental setup. We developed an image-based approach suitable to screen large numbers of drugs, using a cell line that can be infected by HBV and produces large amounts of virus particles. By transferring viral supernatants from these infected cells to uninfected target cells, we could monitor the entire viral life cycle. We used this system to screen drug libraries and identified novel anti-HBV inhibitors that potently inhibit HBV in various phases of its life cycle. This assay will be an important new tool to study the HBV life cycle and accelerate the development of novel therapeutic strategies.

Territorywide Study of Early Coronavirus Disease Outbreak, Hong Kong, China.

Initial cases of coronavirus disease in Hong Kong were imported from mainland China. A dramatic increase in case numbers was seen in February 2020. Most case-patients had no recent travel history, suggesting the presence of transmission chains in the local community. We collected demographic, clinical, and epidemiologic data from 50 patients, who accounted for 53.8% of total reported case-patients as of February 28, 2020. We performed whole-genome sequencing to determine phylogenetic relationship and transmission dynamics of severe acute respiratory syndrome coronavirus 2 infections. By using phylogenetic analysis, we attributed the community outbreak to 2 lineages; 1 harbored a common mutation, Orf3a-G251V, and accounted for 88.0% of the cases in our study. The estimated time to the most recent common ancestor of local coronavirus disease outbreak was December 24, 2019, with an evolutionary rate of 3.04 × 10-3 substitutions/site/year. The reproduction number was 1.84, indicating ongoing community spread.

Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs.

Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC50s), and in particular, two FDA-approved drugs-niclosamide and ciclesonide-were notable in some respects.