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Background: Promoting COVID-19 prevention is key to pandemic control and innovative interventions can help communicate reliable science to the public. Under the Hong Kong Jockey Club SMART Family-Link Project, we developed and evaluated a pilot intervention for promoting COVID-19 prevention through a web-based family game, guided by the Theory of Planned Behavior and a strength-based approach. Methods: The "SMART Epidemic prevention" pilot theme was launched to the public on September 21, 2020 for 4 weeks. The game had two parts: (i) strength recognition and (ii) quiz questions on knowledge and behaviors about COVID-19 prevention. Simple baseline, in-game, and postgame evaluation assessed players' perceived knowledge, behaviors, family well-being, game satisfaction, and perceived benefits. Results: Of 86 registered families, 55 played actively, including 212 players (51% female, 35% aged below 18) who self-identified as children (44%), parents (39%), and grandparents (11%). In weeks 1 and 4, an average of 7 and 18 game rounds were played per family, and 86.6% and 75.9% of rounds had perfect (2) behavior matches. Postgame evaluation with 51 families showed improvements in epidemic prevention knowledge and behaviors, family communication, family happiness (all P  < 0.001), and family relationship ( P  = 0.002) with small effect sizes (0.15-0.29). Overall game satisfaction was rated 4.49 (scale of 1-5). Ninety-four percent of families shared knowledge from the game with others. Conclusions: Our pilot web-based family game first showed preliminary evidence on enhancing COVID-19 prevention knowledge and behaviors, and family well-being, with participants recognizing family strengths, reporting high satisfaction and various perceived benefits, and showing sustained gameplay. Trial Registration: The research protocol was registered at the National Institutes of Health (Identifier No. NCT04550065) on September 16, 2020.

The BIOFIRE SPOTFIRE Respiratory (R) Panel is a novel, in vitro diagnostic PCR assay with 15 pathogen targets. The runtime is about 15 min which is the shortest among similar panels in the market. We evaluated the performance of the SPOTFIRE R Panel with 151 specimens, including 133 collected from the upper respiratory tract (URT), 13 from the lower respiratory tract (LRT) and 5 external quality assessment program (EQAP) samples. The respiratory specimens were enrolled throughout the first two post-COVID-19 influenza seasons in Hong Kong (March to December 2023). For URT specimens, full concordance was observed between the SPOTFIRE R Panel and the standard-of-care FilmArray Respiratory 2.1 plus Panel (RP2.1 plus ) for 109 specimens (109/133, 81.95%). After discrepant analysis, the SPOTFIRE R Panel identified more pathogens than the RP2.1 plus in 15 specimens and vice versa in 3 specimens. The per-target negative and positive percentage agreement (NPA and PPA) were 92.86-100% except the PPA of adenovirus (88.24%). For LRT and EQAP samples, all results were fully concordant. To conclude, the performance of the SPOTFIRE R Panel was comparable to the RP2.1 plus .

Background: Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary. Fractional dosing by intradermal (ID) administration has been shown to be equally immunogenic as intramuscular (IM) administration for several vaccines, but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents., Methods: Participants aged 11-17 years received two doses of IM or ID vaccine, followed by the 3rd dose 13-42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively., Results: Spike protein (S) immunoglobulin G (IgG), S-receptor-binding domain (RBD) IgG, S IgG Fcγ receptor IIIa (FcγRIIIa)-binding, SNM [sum of individual (S), nucleocapsid protein (N), and membrane protein (M) peptide pool]-specific interleukin-2 (IL-2) + CD4 + , SNM-specific IL-2 + CD8 + , S-specific IL-2 + CD8 + , N-specific IL-2 + CD4 + , N-specific IL-2 + CD8 + and M-specific IL-2 + CD4 + responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test, 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2 + CD4 + , interferon-γ + CD8 + and IL-2 + CD8 + responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. The ID groups reported more local, mild adverse reactions., Conclusion: This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines., (© 2023. The Author(s).)

Background: Pneumothorax, pneumomediastinum and subcutaneous emphysema are respiratory complications of Coronavirus disease 2019 occurring with noteworthy frequency in patients especially with severe disease. They can be life-threatening and often complicate patient managment., Methods: This was a retrospective, observational study of patients admitted in Nepal Armed Police Force hospital from 13/05/2020 to 28/12/2021 diagnosed with pneumothorax, pneumomediastinum or subcutaneous emphysema singly or in combination. Data were collected from clinical charts, imaging records and electronic medical records of Severe Acute Respiratory Syndrome Coronavirus-type 2 positive patients 18 years and older. The frequency and type of the defined complications, the inflammatory markers and ventilatory parameters just prior to their diagnosis, the duration of hospitalization and ICU admission and in-hospital mortality rate were studied., Results: Out of 4013 COVID-19 patients admitted in the hospital during the period, a total of 28 patients were observed to develop the complications, the overall incidence being 0.7% among hospitalized patients and 5.6% among ICU patients. The proportion of subcutaneous emphysema (64.3%) was highest followed by pneumomediastinum (46.4%) and then pneumothorax (39.3%) existing singly or in combination among the 28 patients, where four patients developed the complications spontaneously. Mean Positive End Expiratory Pressure of 12.1±2.6 cmH2O and Peak Inspiratory Pressure or Pressure Support of 30.9±10.3 cmH2O were observed for patients under positive pressure ventilation. Most of the patients who developed the complications (78.6%) died during treatment., Conclusions: Pulmonary air leak complications occur frequently in COVID-19 patients treated with or without positive pressure ventilation signifying increased disease severity, risk of ICU admission and high mortality rate. Hence, clinicians should be vigilant of these complications in all patients affected with COVID-19 and institute timely management.

Background: While the advanced health care settings are struggling hard to handle the sudden surge of COVID-19 cases, resource poor settings in developing countries like Nepal can barely stand to fight the increasing number of severe cases. Easily available cost effective interventions would be great blessing for such settings. This study aimed to study if awake prone positioning can be used as such intervention in COVID 19., Methods: The retrospective study involved 150 patients admitted between November 2020 and January 2021 at Nepal Armed Police Force Hospital and met specific inclusion criteria. Data was obtained at four different time points in relation to prone position and was analysed using International Business Machines Statistical Package for the Social Sciences (SPSS) version 23., Results: It was found that among 150 patients, majority (109; 72.7%) were males and 60(40%) had some comorbidities. The mean oxygen saturation was found to increase significantly from 87.18 %(SD 3.531) to 91.08(SD 2.206) after fifteen minutes of prone positioning. One way ANOVA test showed that there was significant difference in oxygen saturation between at least two time points. (F (3,596) = [180.005], p=0.000). Games Howell Post Hoc test for multiple comparisons showed that the mean value of SPO-2 was significantly different across all four time points, at significance level 0.05., Conclusions: This study found Awake Prone positioning as a promising cost effective and feasible intervention for improving oxygenation in COVID 19 and thus could be a blessing to the resource poor health care settings.

This study aimed to assess the efficacy of a guided online mindfulness-based intervention (iMBI) for community residents experiencing emotional distress during the COVID-19 pandemic in Hong Kong. In a randomized controlled trial, 64 participants were recruited from collaborating community-based mental health service units in Hong Kong and assigned to either the treatment (n = 32) or control (n = 32) groups. The treatment group received a guided iMBI consisting of 16 online modules, weekly telephone counseling, and two half-day online workshops on mindfulness practice. In contrast, the waitlist control group did not receive any intervention during the initial stage. Using a 2 (two groups) × time (pre versus post) repeated measures linear mixed model and one-way analysis of variance, authors demonstrated that the treatment group experienced a significantly larger reduction in anxiety and depressive symptoms with a large effect size compared with the control group. Additionally, the treatment group showed a significantly greater improvement in mindfulness with a moderate effect size. The findings support the effectiveness of guided iMBI for community residents experiencing emotional distress during the COVID-19 pandemic in Hong Kong., (© 2024 National Association of Social Workers.)

The mRNA-based BNT162b2 and inactivated whole-virus CoronaVac are two widely used COVID-19 vaccines that confer immune protection to healthy individuals. However, hesitancy toward COVID-19 vaccination appeared to be common for patients with neuromuscular diseases (NMDs) due to the paucity of data on the safety and efficacy in this high-risk patient population. Therefore, we examined the underlying factors associated with vaccine hesitancy across time for NMDs and assessed the reactogenicity and immunogenicity of these two vaccines. Patients aged 8-18 years with no cognitive delay were invited to complete surveys in January and April 2022. Patients aged 2-21 years were enrolled for COVID-19 vaccination between June 2021 and April 2022, and they recorded adverse reactions (ARs) for 7 days after vaccination. Peripheral blood was obtained before and within 49 days after vaccination to measure serological antibody responses compared to healthy children and adolescents. Forty-one patients completed vaccine hesitancy surveys for both timepoints, while 22 joined the reactogenicity and immunogenicity arm of the study. Two or more family members vaccinated against COVID-19 was positively associated with intention of vaccination (odds ratio 11.7, 95% CI 1.81-75.1, p  = .010). Pain at the injection site, fatigue, and myalgia were the commonest ARs. Most ARs were mild (75.5%, n  = 71/94). All 19 patients seroconverted against the wildtype SARS-CoV-2 after two doses of either vaccine, similar to 280 healthy counterparts. There was lower neutralization against the Omicron BA.1 variant. BNT162b2 and CoronaVac were safe and immunogenic for patients with NMDs, even in those on low-dose corticosteroids.

Depressive symptoms have been commonly reported in older adults during the coronavirus disease (COVID-19) pandemic. Social isolation as a result of social distancing to prevent COVID-19 was reported to increase the level of depressive symptoms both directly and indirectly through the mediating effect of loneliness. Depressive symptoms in older adults can be regulated through health behaviors such as physical activity. Therefore, this study used a moderated mediation model to explain depressive symptoms. The English Longitudinal Study of Ageing COVID-19 wave 2 data were used. A total of 296 individuals were excluded due to missing values, leaving a final sample of 6499. Depressive symptoms, social isolation, loneliness, and physical activity were used in the moderated mediation analysis with various demographic and general health variables as covariates. Loneliness was found to significantly mediate the relationship between social isolation and depression. While moderate physical activity significantly moderated the effects of social isolation and loneliness on depressive symptoms, mild physical activity alone significantly moderated the effects of loneliness on depressive symptoms. This study revealed the impact of social isolation on depressive symptoms directly and indirectly mediated by loneliness, with a moderating effect of moderate and mild physical activity in the elderly during COVID-19 in a moderated mediation model.

How do citizens choose COVID-19 vaccines, and when do they wish to be vaccinated? A choice-based conjoint experiment was conducted in Hong Kong to examine factors that shape citizens' preference toward COVID-19 vaccines and their time preference to be vaccinated, which is overlooked in extant literature. Results suggest people are most concerned about vaccines' efficacy and severe side-effects, and that cash incentives are not useful in enhancing vaccine appeal. The majority of respondents show low intention for immediate vaccination, and many of them want to delay their vaccination. Further analysis shows that their time preference is shaped more by respondent characteristics than vaccine attributes. In particular, confidence in the vaccine, trust in government, and working in high-risk professions are associated with earlier timing for vaccine uptake. Meanwhile, forced COVID testing would delay vaccination. The findings offer a novel view in understanding how people decide whether and when to receive new vaccines, which have pivotal implications for a head start of any mass vaccination programs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Clinical trials in humans are vital to test safety and efficacy of new interventions and are accompanied with the complexity of related regulatory guidelines, stringent time frame and financial burden particularly when participants are children. Conducting clinical trials in low and middle income countries, where 90% of global diseases occur, increases the complexity as resources, infrastructures, and experience related to clinical trials may be limited in some countries. During the COVID-19 pandemic, due to multiple infection control measures such as social distancing, lock-down of the societies, and increased work load of hospital workers, conducting clinical trials seemed very challenging. Related guidelines and recommendations on clinical trials required updates to adapt the situation for ongoing clinical trials to be continued and new clinical trials to be initiated. In this review report, we described the lessons learnt through our experiences, challenges we faced, and the mitigation measures implemented as a response while conducting a phase III clinical trial on a non-COVID-19 vaccine at a government children's hospital during the COVID-19 pandemic. We hope this report will contribute in lowering the obstacles to allow the successful completion of future studies, in countries where people live with the burden of vaccine-preventable diseases.

Background: Patients recovering from COVID-19 may need vaccination against SARS-CoV-2 because acquired immunity from primary infection may wane, given the emergence of new SARS-CoV-2 variants. Understanding the trends of anti-spike IgG and neutralizing antibody titers in patients recovering from COVID-19 may inform the decision made on the appropriate interval between recovery and vaccination., Methods: Participants aged 20 years or older and diagnosed with COVID-19 between January and December, 2020 were enrolled. Serum specimens were collected every three months from 10 days to 12 months after the onset of symptom for determinations of anti-spike IgG and neutralizing antibody titers against SARS-CoV-2 Wuhan strain with D614G mutation, alpha, gamma and delta variants., Results: Of 19 participants, we found a decreasing trend of geometric mean titers of anti-spike IgG from 560.9 to 217 and 92 BAU/mL after a 4-month and a 7-month follow-up, respectively. The anti-spike IgG titers declined more quickly in the ten participants with severe or critical disease than the nine participants with only mild to moderate disease between one month and seven months after SARS-CoV-2 infection (-8.49 vs - 2.34-fold, p < 0.001). The neutralizing activity of the convalescent serum specimens collected from participants recovering from wild-type SARS-CoV-2 infection against different variants was lower, especially against the delta variants (p < 0.01 for each variant with Wuhan strain as reference)., Conclusion: Acquired immunity from primary infection with SARS-CoV-2 waned within 4-7 months in COVID-19 patients, and neutralizing cross-activities against different SARS-CoV-2 variants were lower compared with those against wild-type strain., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2022. Published by Elsevier B.V.)

Background: Studies correlating reactogenicity and immunogenicity of COVID-19 vaccines are limited to BNT162b2, with inconsistent results. We investigated whether adverse reactions after other COVID-19 vaccines reliably predict humoral responses., Methods: Adult volunteers were recruited for homologous or heterologous prime-boost vaccinations with adenoviral (ChAdOx1, AstraZeneca) and/or mRNA (mRNA-1273, Moderna) vaccines administered either 4 or 8 weeks apart. Adverse effects were routinely solicited and recorded by subjects in a standard diary card for up to 84 days post booster vaccination. Anti-SARS-CoV-2 IgG titers were measured pre- (visit 1), and post-booster dose at days 14 (visit 2) and 28 (visit 3)., Results: A total of 399 participants (75% women) with a median age of 41 (interquartile range, 33-48 IQR) years were included. Vaccine-induced antibody titers at days 14 and 28 were significantly higher among subjects who reported local erythema, swelling, pain, as well as systemic fever, chills, headache, myalgia, arthralgia, fatigue compared to those who did not experience local or systemic reactogenicity. Post-vaccination humoral responses did not correlate with the occurrence of skin rash and correlated weakly with gastrointestinal symptoms. A significant correlation between post-vaccination peak body temperature and anti-SARS-CoV-2 spike IgG at Day 14, independent of vaccine type and schedule, was found., Conclusion: Specific symptoms of reactogenicity such as post-vaccination injection site pain, swelling, erythema and fever, myalgia and fatigue are significantly predictive of the magnitude of the anti-SARS-CoV-2 antibody response., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Povidone-iodine (PVP-I) inactivates a broad range of pathogens. Despite its widespread use over decades, the safety of PVP-I remains controversial. Its extended use in the current SARS-CoV-2 virus pandemic urges the need to clarify safety features of PVP-I on a cellular level. Our investigation in epithelial, mesothelial, endothelial, and innate immune cells revealed that the toxicity of PVP-I is caused by diatomic iodine (I 2 ), which is rapidly released from PVP-I to fuel organic halogenation with fast first-order kinetics. Eukaryotic toxicity manifests at below clinically used concentrations with a threshold of 0.1% PVP-I (wt/vol), equalling 1 mM of total available I 2 Above this threshold, membrane disruption, loss of mitochondrial membrane potential, and abolition of oxidative phosphorylation induce a rapid form of cell death we propose to term iodoptosis. Furthermore, PVP-I attacks lipid rafts, leading to the failure of tight junctions and thereby compromising the barrier functions of surface-lining cells. Thus, the therapeutic window of PVP-I is considerably narrower than commonly believed. Our findings urge the reappraisal of PVP-I in clinical practice to avert unwarranted toxicity whilst safeguarding its benefits., (© 2023 Steins et al.)

Introduction: Two doses of inactivated SARS-CoV-2 vaccine CoronaVac cannot elicit high efficacy against symptomatic COVID-19, especially against the Omicron variant, but that can be improved by a third dose in adults. The use of a third dose of CoronaVac in adolescents may be supported by immunobridging studies in the absence of efficacy data., Methods: With an immunobridging design, our study (NCT04800133) tested the non-inferiority of the binding and neutralizing antibodies and T cell responses induced by a third dose of CoronaVac in healthy adolescents (N=94, median age 14.2 years, 56% male) compared to adults (N=153, median age 48.1 years, 44% male). Responses against wild-type (WT) and BA.1 SARS-CoV-2 were compared in adolescents. Safety and reactogenicity were also monitored., Results: A homologous third dose of CoronaVac further enhanced antibody response in adolescents compared to just 2 doses. Adolescents mounted non-inferior antibody and T cell responses compared to adults. Although S IgG and neutralizing antibody responses to BA.1 were lower than to WT, they remained detectable in 96% and 86% of adolescents. T cell responses to peptide pools spanning only the mutations of BA.1 S, N and M in adolescents were preserved, increased, and halved compared to WT respectively. No safety concerns were identified., Discussion: The primary vaccination series of inactivated SARS-CoV-2 vaccines for adolescents should include 3 doses for improved humoral immunogenicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Leung, Cohen, Mu, Rosa Duque, Cheng, Wang, Wang, Zhang, Zhang, Tam, Lam, Chan, Chaothai, Kwan, Chan, Li, Luk, Tsang, Chu, Wong, Mori, Leung, Valkenburg, Peiris, Tu and Lau.)

Background: Persons with suicidality including suicidal ideation (SI), suicide plans (SP) and/or suicide attempts (SA) are at higher risk for future suicide than those without suicidality. To reduce the risk of future suicide, it is important to understand symptoms of emotional distress that have the strongest links with SI, SP and SA. This network analysis examined item-level relations of depressive and anxiety symptoms with suicidality among adolescents during the COVID-19 pandemic., Methods: Adolescents between 12 and 20 years of age were assessed with the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and individual binary reponse (no/yes) items assessing SI, SP, and SA during the pandemic. The structure of depressive symptoms, anxiety symptoms and suicidality was characterized using "Expected Influence" and "Bridge Expected Influence" as centrality indices in the symptom network. Network stability was tested using a case-dropping bootstrap procedure. Node-specific predictive betweenness was computed to examine short paths of anhedonia, other depressive symptoms and anxiety symptoms with suicidality. A Network Comparison Test (NCT) was conducted to examine whether network characteristics differed based on gender., Results: Prevalence rates of depressive symptoms, anxiety symptoms, and suicidality were 44.60 % (95% confidence interval (CI) = 41.53-47.67 %), 31.12 % (95%CI = 28.26-33.98 %), and 16.95 % (95%CI = 14.63-19.26 %), respectively, in the study sample. The network analysis identified GAD3 ("Worry too much") as the most central symptom, followed by GAD6 ("Irritability") and PHQ6 ("Guilt") in the sample. Additionally, PHQ6 ("Guilt"), GAD6 ("Irritability"), and PHQ2 ("Sad mood") were bridge nodes linking depressive and anxiety symptoms with suicidality. A flow network indicated that the connection between S ("Suicidality") and PHQ6 ("Guilt") reflected the strongest connection, followed by connections of S ("Suicidality") with GAD2 ("Uncontrollable worrying"), and S ("Suicidality") with PHQ2 ("Sad mood"). Finally, PHQ2 ("Sad mood") was the main bridge node linking anhedonia with other depressive and anxiety symptoms and suicidality in the sample., Conclusions: Findings highlight the potential importance of reducing specific depressive and anxiety symptoms as possible means of reducing suicidality among adolescents during the pandemic. Central symptoms and key bridge symptoms identified in this study should be targeted in suicide prevention for at-risk adolescents., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Asthma is a chronic respiratory condition that affects 10% of Canadian children and is often exacerbated by viral respiratory infections, prompting concerns about the severity of SARS-CoV-2 disease in children with asthma. We compared sociodemographic and clinical characteristics of children presenting to the emergency department and the incidence of these visits, before and during the pandemic., Methods: We included children aged 0 to 17 years presenting with asthma to 2 tertiary pediatric emergency departments in Montréal, Quebec, between the prepandemic (Jan. 1, 2017, to Mar. 31, 2020) and pandemic (Apr. 1, 2020, to June 30, 2021) periods. We compared the number of emergency department visits and hospital admissions with an interrupted time series analysis and compared the sociodemographic characteristics based on the Canadian Index of Multiple Deprivation (CIMD) and clinical characteristics (including triage level, intensive care admissions, etc.) with Mann-Whitney and χ 2 tests., Results: We examined 22 746 asthma-related emergency department visits. During the pandemic, a greater proportion of patients presented a triage level 1 or 2 (19.3% v. 14.7%) and were admitted to the intensive care unit (2.5% v. 1.3%). The patients' CIMD quintile distributions did not differ between the 2 periods. We found a 47% decrease (relative risk [RR] 0.53, 95% confidence interval [CI] 0.37 to 0.76) in emergency department visits and a 49% decrease (RR 0.51, 95% CI 0.34 to 0.76) in hospital admissions during the pandemic., Interpretation: The decrease in asthma-related emergency department visits was observed through the third wave of the pandemic, but children presented with a higher acuity and with no identified sociodemographic changes. Future studies are required to understand individual behaviours that may have led to the increased acuity at presentation observed in this study., Competing Interests: Competing interests: None declared., (© 2023 CMA Impact Inc. or its licensors.)

The appropriate interval between heterologous prime adenoviral vectored vaccination and boost mRNA vaccination remains unclear. We recruited 100 adult participants to receive a prime adenoviral vectored vaccine (ChAdOx1, AstraZeneca) and a boost mRNA vaccine (mRNA-1273, Moderna) 12 weeks apart and checked their serum SARS-CoV-2 anti-spike IgG titers and neutralizing antibody titers against B.1.1.7 (alpha) and B.1.617.2 (delta) variants on the 28 th day after the boost dose. Results were compared with our previous study cohorts who received the same prime-boost vaccinations at 4- and 8-week intervals. Compared to other heterologous vaccination groups, the 12-week interval group had higher neutralizing antibody titers against SARS-CoV-2 variants than the 4-week interval group and was similar to the 8-week interval group at day 28. Adverse reactions after the boost dose were mild and transient. Our results support deploying viral vectored and mRNA vaccines in a flexible schedule with intervals from 8 to 12 weeks., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background/purpose: The efficacy and safety of coronavirus disease 2019 (COVID-19) booster vaccines remain limited. We investigated the immunogenicity and adverse events of the third dose of mRNA vaccines in healthy adults., Methods: Volunteers vaccinated with two doses of the adenoviral vaccine (ChAdOx1) 12 weeks before were administered with an mRNA COVID-19 vaccine. These were divided into three groups, full-dose mRNA-1273 (group 1); half-dose mRNA-1273 (group 2); and full-dose BNT-162b2 (group 3). Primary outcomes included serum anti-SARS-CoV-2 spike immunoglobulin G (IgG) titers and neutralizing antibody titers against B.1.1.7 (alpha), B.1.617.2 (delta), and B.1.1.529 (omicron) variants. Secondary outcomes included the evaluation of humoral and cellular immunity and vaccine-associated adverse events after the boost., Results: Totally 300 participants were recruited, and 298 participants were enrolled. For all three groups, an increase in anti-SARS-CoV-2 spike IgG geometric mean titers (30.12- to 71.80-fold) and neutralizing antibody titers against the alpha variant (69.80- to 173.23-folds), delta variant (132.69- to 324.63-folds), and omicron variant (135.36- to 222.37-folds) were observed on day 28. All groups showed robust T- and B-cell responses after boosting. Adverse events were overall mild and transient but with higher prevalence and severity in group 1 participants than in other groups., Conclusion: Third dose mRNA COVID-19 vaccines markedly enhanced cellular and humoral responses and were safe. Immunological responses and adverse events were higher in individuals receiving the full-dose mRNA-1273 vaccine, followed by a half-dose mRNA-1273 vaccine and BNT-162b2 vaccine., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article, (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

We reported 25 recipients (14 females and 11 males) aged from 18 to 65 years who unexpectedly received a primary dose of undiluted BNT162b2 vaccine (180 μg). The most common adverse reactions included injection site pain (n = 22), followed by fever (9), fatigue (8), chest tightness (6), and dizziness (6). The most common laboratory abnormalities were anemia (n = 4) and elevated liver transaminase level (4), followed by abnormal leukocyte counts (3) and elevated D-dimer level (3). The adverse reactions and laboratory abnormalities of these recipients were mild and spontaneously recovered within a few weeks. Significant elevations of anti-SARS-CoV-2 spike IgG titers after a booster dose of the BNT162b2 were found. Similar to reports of BNT162b2 clinical trials, the adverse reactions and laboratory abnormalities of these recipients were mild, and they spontaneously recovered within a few weeks. These results provide clinical and immunological effects of undiluted BNT162b2 vaccine inoculation., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

The high effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported in some studies, but immune responses conferring this protection are not yet elucidated. In this analysis, our study (NCT04800133) aims to evaluate the humoral and cellular responses against wild-type and Omicron (BA.1, BA.2 and/or BA.5) SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents. At 5 months after 2 doses, S IgG, S IgG Fc receptor-binding, and neutralising antibody responses waned significantly, yet neutralising antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses. The antibody responses and S-specific IFN-γ + and IL-2 + CD8 + T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2. Compared to adults, humoral responses for the third dose were non-inferior or superior in adolescents. The S-specific IFN-γ + and IL-2 + CD4 + and CD8 + T cell responses in adolescents and adults were comparable or non-inferior. Interestingly, after 3 doses, adolescents had preserved S IgG, S IgG avidity, S IgG FcγRIIIa-binding, against Omicron BA.2, as well as preserved cellular responses against BA.1 S and moderate neutralisation levels against BA.1, BA.2 and BA.5. Sera from 100 and 96% of adolescents tested at 1 and 5 months after two doses could also neutralise BA.1. Our study found high antibody and T cell responses, including potent cross-variant reactivity, after three doses of BNT162b2 vaccine in adolescents in its current formulation, suggesting that current vaccines can be protective against symptomatic Omicron disease., (© 2022. The Author(s).)

Background: Whether immunocompromising conditions affect the immunogenicity of COVID-19 booster vaccination remains a concern, which impedes the vaccination campaign in people most vulnerable to COVID-19-associated morbidity and mortality. We aimed to evaluate the effect of immune dysfunction on immunogenicity of homologous and heterologous prime-boost COVID-19 vaccination., Methods: Between July and August, 2021, 399 participants were randomized to receive ChAdOx1/ChAdOx1 8 weeks apart, ChAdOx1/mRNA-1273 8 weeks apart, ChAdOx1/mRNA-1273 4 weeks apart, and mRNA-1273/mRNA-1273 4 weeks apart. The anti-SARS-CoV-2 spike IgG antibody titers on the day before booster vaccination and 4 weeks after booster vaccination were compared between participants with and without immunocompromising conditions., Results: Among ChAdOx1-primed participants, a trend of lower anti-SARS-CoV-2 spike IgG titers before booster vaccination were found in participants with autoimmune diseases (geometric means, 34.76 vs. 84.25 binding antibody units [BAU]/mL, P = 0.173), compared to those without. Participants receiving immunosuppressants and/or immunomodulators had significant lower anti-SARS-CoV-2 spike IgG titers before booster vaccination than those without (geometric means, 36.39 vs. 83.84 BAU/mL; P = 0.001). Among mRNA-1273-boosted participants, anti-SARS-CoV-2 spike IgG titers 4 weeks after booster vaccination were similar across all the strata. Participants with autoimmune diseases and receiving immunosuppressants and/or immunomodulators, had numerically lower anti-SARS-CoV-2 spike IgG titers 4 weeks after booster vaccination compared to those without (geometric means, 1474.34 vs. 1923.23 and 1590.61 vs. 1918.38 BAU/mL; P > 0.05)., Conclusion: The immunogenicity of prime vaccination with ChAdOx1 decreased by immune dysfunction, but enhanced after receiving boost vaccination with mRNA-1273. Our study results support the efficacy of mRNA-1273 booster dose among immunocompromised hosts., Competing Interests: Conflict of Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

Our study (NCT04800133) aimed to determine the safety and immunogenicity in patients with IEIs receiving a 3-dose primary series of mRNA vaccine BNT162b2 (age 12+) or inactivated whole-virion vaccine CoronaVac (age 3+) in Hong Kong, including Omicron BA.1 neutralization, in a nonrandomized manner. Intradermal vaccination was also studied. Thirty-nine patients were vaccinated, including 16 with homologous intramuscular 0.3ml BNT162b2 and 17 with homologous intramuscular 0.5ml CoronaVac. Two patients received 3 doses of intradermal 0.5ml CoronaVac, and 4 patients received 2 doses of intramuscular BNT162b2 and the third dose with intradermal BNT162b2. No safety concerns were identified. Inadequate S-RBD IgG and surrogate virus neutralization responses were found after 2 doses in patients with humoral immunodeficiencies and especially so against BA.1. Dose 3 of either vaccine increased S-RBD IgG response. T cell responses against SARS-CoV-2 antigens were detected in vaccinated IEI patients by intracellular cytokine staining on flow cytometry. Intradermal third dose vaccine led to high antibody response in 4 patients. The primary vaccination series of BNT162b2 and CoronaVac in adults and children with IEIs should include 3 doses for optimal immunogenicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Leung, Mu, Duque, Cheng, Wang, Zhang, Zhang, Tam, Lee, Lam, Chan, Cheang, Chung, Wong, Lee, Li, Chaothai, Tsang, Chua, Cheong, Au, Kwok, Chan, Chong, Lee, Ho, Lee, Tu, Peiris and Lau.)

The present study aimed to analyze changes in health-related physical fitness among Korean elementary and middle school students before (2019) and after (2021) the COVID-19 pandemic. Data collection was completed by requesting the physical activity promotion system (PAPS) data from elementary and middle school students. This information is obtained annually by the Goyang Office of Education in Gyeonggi-do, Korea. The collected data were measured in 2019 and 2021. Data were collected from 17,000 children in the fifth and sixth grades of elementary school and about 24,000 boys and girls in the first, second, and third grades of middle school. Chi-square analyses were used to examine data from each school's health-related physical fitness examinations. Our results indicated that physical fitness levels were significantly lower in 2021 than in 2019 across the following six areas: cardiorespiratory endurance, power, muscular strength, flexibility, obesity, and overall health-related physical fitness ( p < 0.05). In addition, the ratio of students with excellent physical fitness (PAPS Grades 1 and 2) significantly decreased from 2019 to 2021, while the ratio of students with poor physical fitness (PAPS Grades 3, 4, and 5) increased ( p < 0.05). In addition, there were some differences according to grade and gender. Discussions regarding the impact of decreases in physical activity on physical fitness, interpretations of physical fitness in the context of a pandemic, and practical measures that can be implemented to improve health and fitness among children and adolescents in such situations remain essential.

Background: The coronavirus disease 2019 (COVID-19) pandemic disrupted the working lives of Macau residents, possibly leading to mental health issues such as depression. The pandemic served as the context for this investigation of the network structure of depressive symptoms in a community sample. This study aimed to identify the backbone symptoms of depression and to propose an intervention target., Methods: This study recruited a convenience sample of 975 Macao residents between 20th August and 9th November 2020. In an electronic survey, depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9). Symptom relationships and centrality indices were identified using directed and undirected network estimation methods. The undirected network was constructed using the extended Bayesian information criterion (EBIC) model, and the directed network was constructed using the Triangulated Maximally Filtered Graph (TMFG) method. The stability of the centrality indices was evaluated by a case-dropping bootstrap procedure. Wilcoxon signed rank tests of the centrality indices were used to assess whether the network structure was invariant between age and gender groups., Results: Loss of energy, psychomotor problems, and guilt feelings were the symptoms with the highest centrality indices, indicating that these three symptoms were backbone symptoms of depression. The directed graph showed that loss of energy had the highest number of outward projections to other symptoms. The network structure remained stable after randomly dropping 50% of the study sample, and the network structure was invariant by age and gender groups., Conclusion: Loss of energy, psychomotor problems and guilt feelings constituted the three backbone symptoms during the pandemic. Based on centrality and relative influence, loss of energy could be targeted by increasing opportunities for physical activity., Competing Interests: The authors declare that they have no competing interests., (© 2022 Zhao et al.)

Mindfulness-based art therapy has shown to improve psychological well-being. Zentangle is an easy-to-learn, mindfulness-based art therapy suitable for everyone. We reported the transition from face-to-face to online Zentangle workshops in family social services during COVID-19. We explored feedback from face-to-face workshops and the acceptability of an online approach utilizing information communication technology (ICT) to achieve greater service reach, satisfaction, and knowledge and related outcomes. Under the Hong Kong Jockey Club SMART Family-Link Project and in collaboration with Caritas Integrated Family Service Centre-Aberdeen, this study was conducted in two phases: a four-session, face-to-face workshop (phase one) and eleven online single-session workshops (phase two) from September 2019 to September 2020. A total of 305 participants joined the workshops. Phase one participants ( n = 11) reported high satisfaction (4.7 out of 5), increases in knowledge (4.2/5) and confidence (3.9/5) towards managing stress, increases in knowledge (4.1/5) and confidence (3.9/5) in showing support and care towards family members, and an increase in knowledge towards strengthening family relationships (4.0/5). Phase two participants ( n = 294) also reported high satisfaction (4.7/5) and strongly agreed that ICT helped with learning Zentangle more conveniently, that they had increased knowledge and interest in Zentangle (all 4.7/5), and would definitely join the workshop again (4.8/5). The qualitative data supported the quantitative findings. We are the first to report on the utilization of ICT in an exploratory trial of brief, online Zentangle art workshops targeting the general public, with high satisfaction and positive participant experiences with ICT integration, learning Zentangle, and enhanced psychological and family well-being. This study provided preliminary evidence on the use of ICT to successfully transition face-to-face to online workshops and reach a wider audience.

Background: Although the Coronavirus Disease 2019 (COVID-19) has greatly impacted individuals' mental health and quality of life, network analysis studies of associations between symptoms of common syndromes during the pandemic are lacking, particularly among Macau residents. This study investigated the network structure of insomnia, anxiety, and depression and explored their associations with quality of life in this population., Method: This online survey was conducted in Macau between August 18 and November 9, 2020. Insomnia, anxiety, depressive symptoms, and quality of life were assessed with the Insomnia Severity Index, Generalized Anxiety Disorder Scale, Patient Health Questionnaire, and World Health Organization Quality of Life-brief version, respectively. Analyses were performed to identify central symptoms and bridge symptoms of this network and their links to quality of life., Results: 975 participants enrolled in this survey. The prevalence of depressive, anxiety and insomnia symptoms were 38.5% (95% confidence interval (CI): 35.5%-41.5%), 28.8% (95%CI: 26.0%-31.7%), and 27.6% (95% CI: 24.8%-30.4%), respectively. "Sleep maintenance" had the highest expected influence centrality, followed by "Trouble relaxing", "Interference with daytime functioning", "Irritability", and "Fatigue". Five bridge symptoms were identified: "Sleep problems", "Restlessness", "Irritability", "Severity of sleep onset", and "Motor activity". The insomnia symptom, "Sleep dissatisfaction", had the strongest direct relation to quality of life., Conclusion: Insomnia symptoms played a critical role in the distress symptom network regarding node and bridge centrality as well as associations with quality of life among Macau residents. Close attention to these symptoms may be critical to reducing risk and preventing exacerbations in common forms of distress in this population., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Recreational activities such as physical and social activities are key components of a healthy life for the elderly. Since the outbreak of Corona 19, leisure facilities such as indoor sports facilities, religious facilities, and cultural facilities have been closed, and group activities such as volunteer activities and clubs are also being held under control. These measures are expected to bring about many changes in the leisure activities of the elderly. In this study, an empirical analysis was made on how COVID-19 caused changes in leisure activities of the elderly using national statistical data. For the data analysis, raw data of the "2019 National Leisure Activities Survey" and "2020 National Leisure Activities Survey" conducted by the Ministry of Culture, Sports and Tourism were used, and data of a total of 5,069 elderly people were analyzed. As for the analysis method, the changes in leisure activities of the elderly before and after COVID-19 in terms of participation rate were compared and analyzed. In addition, the changes in leisure activities of the elderly in terms of the type of leisure activities were examined before and after COVID-19 as well. As a result of the analysis, the participation rate in sports activities, hobbies and entertainment activities, and leisure activities increased, while the participation rates in culture and art viewing and participation activities, sports viewing activities, tourism activities, and social activities decreased. In particular, it was found that the proportion of the elderly spending leisure time centered on active and social activities decreased, and the proportion of the elderly consuming leisure time centered on passive activities increased. As a result, it was found that the leisure activities of the elderly are changing passively due to COVID-19. Leisure support policies for active leisure activities of the elderly are likely to be necessary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Park and Kang.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets lipid-producing cells for viral tropism. In this review, we connect systemic lipid couriers, particularly high-density lipoproteins (HDLs) and exosomes, with the neurological facets of SARS-CoV-2 infection. We discuss how SARS-CoV-2 preferentially targets lipid-secreting cells and usurps host cell lipid metabolism for efficient replication and systemic spreading. Besides providing natural veils for viral materials against host immunity, the inherent properties of some of these endogenous lipid particles to traverse the blood-brain barrier (BBB) also offer alternative routes for SARS-CoV-2 neurotropism. Importantly, virus-driven neurological aberrations mediated by HDLs and exosomes are fueled by lipid rafts, which are implicated in the production and transmigration of these lipid particles across the BBB. Finally, we discuss how repurposing existing drugs targeting lipid rafts and cholesterol homeostasis may be beneficial toward alleviating the global coronavirus disease 2019 (COVID-19) disease burden., Competing Interests: Declaration of interests S.M.L. is an employee of LipidALL Technologies. G.S. receives research funding from the Agilent Applications and Core Technology - University Research. The other author declares no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We present an interim analysis of a registered clinical study (NCT04800133) to establish immunobridging with various antibody and cellular immunity markers and to compare the immunogenicity and reactogenicity of 2-dose BNT162b2 and CoronaVac in healthy adolescents as primary objectives. One-dose BNT162b2, recommended in some localities for risk reduction of myocarditis, is also assessed. Antibodies and T cell immune responses are non-inferior or similar in adolescents receiving 2 doses of BNT162b2 (BB, N = 116) and CoronaVac (CC, N = 123) versus adults after 2 doses of the same vaccine (BB, N = 147; CC, N = 141) but not in adolescents after 1-dose BNT162b2 (B, N = 116). CC induces SARS-CoV-2 N and N C-terminal domain seropositivity in a higher proportion of adolescents than adults. Adverse reactions are mostly mild for both vaccines and more frequent for BNT162b2. We find higher S, neutralising, avidity and Fc receptor-binding antibody responses in adolescents receiving BB than CC, and a similar induction of strong S-specific T cells by the 2 vaccines, in addition to N- and M-specific T cells induced by CoronaVac but not BNT162b2, possibly implying differential durability and cross-variant protection by BNT162b2 and CoronaVac, the 2 most used SARS-CoV-2 vaccines worldwide. Our results support the use of both vaccines in adolescents., (© 2022. The Author(s).)

The COVID-19 pandemic has a unprecedented impact on the way individuals make sense of the interconnected nature of themselves in relation to the world. This study investigated the mediating role of transcendental awareness and compassion in the association of interconnectedness with a sense of civic duty and collective action participation during COVID-19 using a longitudinal design. A total of 336 young adult participants were recruited at baseline and were asked to complete measures of interconnectedness, transcendental awareness, compassion, civic duty, and collective action participation at three time points over a 6-month period. Path analysis was used to test the hypothesized mediation model. The results showed that compassion fully mediated the positive association between interconnectedness and collective action participation and partially mediated the positive association between interconnectedness and civic duty. Transcendental awareness also partially mediated the positive association between interconnectedness and civic duty but not collective action participation. This study highlighted the potential of interconnectedness in promoting civic duty and engagement in collective action through transcendental awareness and compassion during the COVID-19 pandemic.

This study aimed to explore the factor structure of the Korean version of the occupational socialization of beginning physical education teachers scale, in the context of the COVID-19 pandemic, and to verify its relationship with health perception education. In October 2021, 257 Korean beginning physical education teachers were enrolled in this study. Data were analyzed using frequency analysis, exploratory factor analysis, confirmatory factor analysis, descriptive statistics, reliability analysis, and multiple regression analysis. Regarding the findings, first, the occupational socialization of beginning physical education teachers scale showed a six-factor structure: role recognition, past physical education class experience, pre-service teacher education, organizational atmosphere, fellow physical education teachers, and sports facility. Second, occupational socialization of beginning physical education teachers showed a partial positive effect on health perception education. These results suggest that the Korean Metropolitan and Provincial Offices of Education and Korean schools should develop various methods to support and ensure the occupational socialization of beginning physical education teachers. Such efforts may enable these new professionals to effectively adapt to their schools, teaching roles, and provide effective health education to students under the difficult context of the COVID-19 pandemic, wherein normal educational activities are hindered.

Background: Speech therapy is important for ideal functional outcome after cleft palate surgery. Nationwide lockdown due to outbreak of COVID-19 in Nepal restricted the ability of patients to travel to nearby outreach centers for regular speech therapy. The objectives were to assess the feasibility and challenges of conducting online speech therapy with postpalatoplasty children during COVID-19 pandemic; and evaluate the ways to overcome them., Methods: Patients with cleft palate surgery done at least 3 months prior were given online speech therapy. Feasibility, advantages and challenges of online speech therapy were evaluated through interviewing the guardians and speech therapy providers., Results: A total of 89 patients were included in the study. Only 11.2% had secondary palatine procedures. Almost all the children (97.8%) had face to face speech therapy prior to study period. Best use of time, use of audiovisual aid, no need to travel and rapid progress were the most commonly perceived strengths of online speech therapy. The most frequent challenges were internet connectivity, unclear voice, lack of direct interaction and unstable power supply. Recommended ways to improve online speech therapy were cited as better internet connectivity, having a fixed schedule and availing free or affordable Wifi., Conclusions: Despite the challenges, online speech therapy provided us with a way to reach out to the cleft palate children when face-to-face therapy was not possible due to COVID-19 pandemic. We see its role even during non-pandemic situations for the children who are unable to visit the speech therapy centers.

Background: Understanding the relative transmissibility of SARS-CoV-2 virus across different contact settings and the possibility of superspreading events is important for prioritizing disease control. Such assessment requires proper consideration of individual level exposure history, which is made possible by contact tracing., Methods: The case-ascertained study in Shandong, China including 97 laboratory-confirmed index cases and 3158 close contacts. All close contacts were quarantined after their last exposure of index cases. Contacts were tested for COVID-19 regularly by PCR to identify both symptomatic and asymptomatic infections. We developed a Bayesian transmission model to the contact tracing data to account for different duration of exposure among individuals to transmission risk in different settings, and the heterogeneity of infectivity of cases., Results: We estimate secondary attack rates (SAR) to be 39% (95% credible interval (CrI): 20-64%) in households, 30% (95% CrI: 11-67%) in healthcare facilities, 23% (95% CrI: 7-51%) at workplaces, and 4% (95% CrI: 1-17%) during air travel. Models allowing heterogeneity of infectivity of cases provided a better goodness-of-fit. We estimated that 64% (95% CrI: 55-72%) of cases did not generate secondary transmissions, and 20% (95% CrI: 15-26%) cases explained 80% of secondary transmissions., Conclusions: Household, healthcare facilities and workplaces are efficient setting for transmission. Timely identification of potential superspreaders in most transmissible settings remains crucial for containing the pandemic., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The COVID-19 pandemic struck the world unguarded, some places outperformed others in COVID-19 containment. This longitudinal study considered a comparative evaluation of COVID-19 containment across 50 distinctly governed regions between March 2020 and November 2021. Our analysis distinguishes between a pre-vaccine phase (March-November 2020) and a vaccinating phase (December 2020-November 2021). In the first phase, we develop an indicator, termed lockdown efficiency (LE), to estimate the efficacy of measures against monthly case numbers. Nine other indicators were considered, including vaccine-related indicators in the second phase. Linear mixed models are used to explore the relationship between each government policy & hygiene education (GP&HE) indicator and each vital health & socioeconomic (VH&SE) measure. Our ranking shows that surveyed countries in Oceania and Asian outperformed countries in other regions for pandemic containment prior to vaccine development. Their success appears to be associated with non-pharmaceutical interventions, acting early, and adjusting policies as needed. After vaccines have been distributed, maintaining non-pharmacological intervention is the best way to achieve protection from variant viral strains, breakthrough infections, waning vaccine efficacy, and vaccine hesitancy limiting of herd immunity. The findings of the study provide insights into the effectiveness of emerging infectious disease containment policies worldwide., (© 2022. The Author(s).)

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on the long-term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC 50 in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by cotreatment in K18-hACE2-transgenic mice, accompanied by a significant prevention of virus-associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggest that C6G25S provides an alternative and effective approach to combating the COVID-19 pandemic., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

The COVID-19 pandemic caused different types of harms and benefits, but the combined patterns of perceived harms and benefits are unclear. We aimed to identify the patterns of perceived harms and benefits of the COVID-19 outbreak and to examine their associations with socio-demographic characteristics, happiness, and changes in smoking and drinking. A population-based cross-sectional online survey was conducted in May 2020 on Hong Kong adults (N = 4520). Patterns of perceived harms and benefits of COVID-19 were identified using latent profile analysis. Their associations with socio-demographic characteristics, happiness, and changes in smoking and drinking were examined using multinomial logistic regression. We identified three distinct patterns: indifferent (66.37%), harm (13.28%), and benefit (20.35%). Compared with the indifferent subgroup, the harm subgroup was younger, less happy, and had increased drinking, and hence might be at higher risk, whereas the benefit subgroup was more likely to be female, live with one or more cohabitants, have postsecondary education, be happier, and have decreased drinking, and could be more adaptive. Future studies can target the harm subgroup to facilitate their positive adjustments.

Background/purpose: Efficacy and safety data of heterologous prime-boost vaccination against SARS-CoV-2 remains limited., Methods: We recruited adult volunteers for homologous or heterologous prime-boost vaccinations with adenoviral (ChAdOx1, AstraZeneca) and/or mRNA (mRNA-1273, Moderna) vaccines. Four groups of prime-boost vaccination schedules were designed: Group 1, ChAdOx1/ChAdOx1 8 weeks apart; Group 2, ChAdOx1/mRNA-1273 8 weeks apart; Group 3, ChAdOx1/mRNA-1273 4 weeks apart; and Group 4, mRNA-1273/mRNA-1273 4 weeks apart. The primary outcome was serum anti-SARS-CoV-2 IgG titers and neutralizing antibody titers against B.1.1.7 (alpha) and B.1.617.2 (delta) variants on day 28 after the second dose. Adverse events were recorded up until 84 days after the second dose., Results: We enrolled 399 participants with a median age of 41 years and 75% were female. On day 28 after the second dose, the anti-SARS-CoV-2 IgG titers of both heterologous vaccinations (Group 2 and Group 3) were significantly higher than that of homologous ChAdOx1 vaccination (Group 1), and comparable with homologous mRNA-1273 vaccination (Group 4). The heterologous vaccination group had better neutralizing antibody responses against the alpha and delta variant as compared to the homologous ChAdOx1 group. Most of the adverse events (AEs) were mild and transient. AEs were less frequent when heterologous boosting was done at 8 weeks rather than at 4 weeks., Conclusion: Heterologous ChAdOx1/mRNA-1273 vaccination provided higher immunogenicity than homologous ChAdOx1 vaccination and comparable immunogenicity with the homologous mRNA-1273 vaccination. Our results support the safety and efficacy of heterologous prime-boost vaccination using the ChAdOx1 and mRNA-1273 COVID-19 vaccines. (ClinicalTrials.gov number, NCT05074368)., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

Family support through the sharing of information helps to shape and regulate the health and behaviours of family members, but little is known about how families are sharing COVID-19-related information, or about its associations with family communication quality and well-being. We examined the associations of COVID-19 information sharing methods with sociodemographic characteristics, the perceived benefits of information communication and technology (ICT) methods, and family communication quality and well-being in Hong Kong. Of 4852 respondents (53.2% female, 41.1% aged over 55 years), the most common sharing method was instant messaging (82.3%), followed by face-to-face communication (65.7%), phone (25.5%) and social media (15.8%). Female sex (adjusted prevalence ratio (aPR) 1.09), older age (aPRs 1.14-1.22) and higher household income (aPR 1.06) (all p ≤ 0.04) were associated with instant messaging use, while post-secondary education was associated with face-to-face (aPR 1.10), video call (aPR 1.79), and email (aPR 2.76) communications (all p ≤ 0.03). Each ICT sharing method used was associated with a higher likelihood of both reported benefits (aPRs 1.26 and 1.52), better family communication quality and family well-being (adjusted βs 0.43 and 0.30) (all p ≤ 0.001). We have first shown that COVID-19 information sharing in families using both traditional methods and ICTs, and using more types of methods, was associated with perceived benefits and better family communication quality and well-being amidst the pandemic. Sociodemographic differences in COVID-19 information sharing using ICTs were observed. Digital training may help enhance social connections and promote family well-being.

Cell death plays an important role during pathogen infections. Here, we report that interferon-γ (IFNγ) sensitizes macrophages to Toll-like receptor (TLR)-induced death that requires macrophage-intrinsic death ligands and caspase-8 enzymatic activity, which trigger the mitochondrial apoptotic effectors, BAX and BAK. The pro-apoptotic caspase-8 substrate BID was dispensable for BAX and BAK activation. Instead, caspase-8 reduced pro-survival BCL-2 transcription and increased inducible nitric oxide synthase (iNOS), thus facilitating BAX and BAK signaling. IFNγ-primed, TLR-induced macrophage killing required iNOS, which licensed apoptotic caspase-8 activity and reduced the BAX and BAK inhibitors, A1 and MCL-1. The deletion of iNOS or caspase-8 limited SARS-CoV-2-induced disease in mice, while caspase-8 caused lethality independent of iNOS in a model of hemophagocytic lymphohistiocytosis. These findings reveal that iNOS selectively licenses programmed cell death, which may explain how nitric oxide impacts disease severity in SARS-CoV-2 infection and other iNOS-associated inflammatory conditions., Competing Interests: Declaration of interests The authors declare that D.S.S., J.P., A.W., I.Y.K., M.R., J.P.C., K.C.D., S.H., H.A., M.D., Y.D., L.M., M.D., A.S.H., S.E.N., J.R.G., M.J.H., E.D.H., A.S., J.S., M.P., R.F., and J.E.V. are employees or former employees of the Walter and Eliza Hall Medical Institute, which receives milestone payments from Genentech and AbbVie for the development of ABT-199 for cancer therapy. J.E.V. sits on the advisory board of Avammune Therapeutics., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The prevalence of and risk factors for uncertainty stress among residents during the COVID-19 pandemic remain unclear. An online cross-sectional survey was conducted to explore and identify the risk factors for high perceived uncertainty stress among the general public in China during the COVID-19 outbreak. Information about the respondents' socioeconomic characteristics, knowledge of and attitudes towards COVID-19, perceived uncertainty stress, social capital, anxiety, and depressive symptoms was collected and analysed. Among the 1205 respondents, 45.3% (546) reported a high level of uncertainty stress. Multiple linear regression analysis indicated that anxiety (β=3.871, P <0.001) and depression symptoms (β=2.458,  P <0.001), family residence (in towns or rural areas) (β=0.947,  P <0.001), lack of support for local epidemic control strategies (β=1.253,  P <0.001), worry about the pandemic (β=1.191,  P <0.001), and symptoms of weakness among family members (β=1.525,  P =0.002) were positively associated with perceived uncertainty stress. Cognitive social capital (β=-0.883,  P <0.001) and social networks (β=-0.726,  P <0.001) were negatively, but social participation (β=0.714,  P <0.001) was positively associated with perceived uncertainty stress. Our findings identify factors associated with a higher level of uncertainty stress and should be helpful in the consideration of effective policies and interventions for uncertainty stress during the initial phases of public health emergencies.

Background: Delaying doctor consultation is harmful. Fear of COVID-19 leads to delays in seeking medical care at a time when pandemic information overflows. However, little is known about the role of COVID-19 related fear, attention to information, and fact-checking in such delay. Objective: Under the Hong Kong Jockey Club SMART Family-Link Project, we examined the associations of delay in doctor consultation amidst the pandemic with sociodemographic characteristics, COVID-19 related fear, attention to information, and fact-checking. Methods: We conducted a population-based online cross-sectional survey in May 2020 on Hong Kong Chinese adults. Respondents reported whether the pandemic caused any delay in doctor consultation (yes/no), level of COVID-19 related fear, attention to information and fact-checking (all on a scale of 0 to 10 and recoded into tertiles of low, moderate, high). Regression analyses were used to examine the associations of delay and fear with sociodemographic characteristics, attention and fact-checking, adjusting for covariates. Data were weighted by sex, age and education level of the population. Results: Of 4,551 respondents (46.5% male, 59.7% aged over 45 years), 10.1% reported delay in doctor consultation. The mean score was 6.4 for fear, 8.0 for attention and 7.4 for fact-checking. Delay was more common in males and increased with age and fear. High vs. low level of fear was associated with delay [adjusted odd ratios (AOR) 2.68, 95% confidence interval (CI) 2.08, 3.47]. Moderate level of fact-checking was negatively associated with delay (AOR 1.28, 95% CI 0.98, 1.67). Females reported greater fear and fear decreased with age. Fear increased with attention to information and decreased with fact-checking. Fear substantially mediated the association of delay with attention (96%) and fact-checking (30%). Conclusions: We have first shown that delay in doctor consultation increased with fear of COVID-19 and decreased with fact-checking amidst the pandemic. Fear also increased with attention to COVID-19 related information and decreased with fact-checking. Understanding these associations can help policymakers develop targeted communication and support to the public to reduce delayed doctor consultations and the associated COVID-19-related or unrelated morbidity and mortality in the community., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lai, Sit, Wu, Wang, Wong, Ho and Lam.)

Aim: The aim of this case study was to assess whether 8 sessions of mobile call based integrated Body-Mind-Spirit (IBMS) intervention could help COVID-19 patient to deal with psychological issues. Methods: This article is based on a practical example of working with COVID-19 patient using the IBMS model. It is a single subject study involving a 50 year old south Indian male living in a Covid Care Center (CCC). Mobile call interviews and brief symptom inventory were used for evaluation. Subject underwent 8 sessions of integrated body-mind-spirit Intervention through video/mobile calls of 45 minutes each time for 8 sessions offered on alternative days over a period of 15 days with pre-post assessments. Results: The results indicate that there was a reduction in somatic symptoms, anxiety and depression on 15th day. Conclusion: Illustrations of real life cases may help psychiatric nurses to gain insight into the application of psycho-social-spiritual interventions through mobile phone during isolation and lockdown.

This study aims to investigate the changes in the structural relationship between alienation in physical education (PE) classes, school happiness, and future healthy life expectations in Korean adolescents after the COVID-19 pandemic. The data were collected from Korean adolescents using different scales. The collected data were analyzed using frequency analysis, reliability analysis, validity analysis, independent t test, and path analysis. The key results were: First, there were partial changes in each of the parameters since the outbreak of COVID-19. Second, before the pandemic, alienation in PE classes negatively affected school happiness, and school happiness positively affected expectations of a future healthy life; however, alienation in PE classes did not affect the expectations of a future healthy life, showing a complete mediating effect. Third, during the pandemic, alienation in PE classes negatively affected school happiness, and school happiness positively affected the expectations of a future healthy life; alienation in PE classes negatively affected the expectations of a future healthy life, showing a partial mediating effect. These findings emphasize the importance and potential of school education, especially PE, in promoting happiness and healthy lives in adolescents. We expect these findings to have practical implications for future research by presenting theoretical and empirical data.

Background: COVID-19 pandemic hit all age group with different presentations and outcome. This study aimed at exploring the clinical characteristics, investigational findings, hospital outcome along with 90 days follow up of COVID-19 infection in children., Methods: This was longitudinal descriptive study among hospital admitted children with COVID-19 RT-PCR positive during first wave of Pandemic with 90 days telephonic follow up. Demographic and clinical characteristics, comorbidities, SPO2, investigations, need of oxygen , PICU admission, need of ventilator, outcome (improved and discharged, death) and duration of hospital stay were recorded and 90 days telephonic follow up was performed for any illness and hospital admission., Results: Out of 65 children admitted, male 44 (67.7%) and female 21 (32.3%), median age was 23 months ( IQR 6 days -14 years) with 52( 80.0%) without any comorbid conditions. The common signs were Fever 40(61.5%) vomiting 15 (23.1%) and Cough 11(16.9%).Thirteen (20.0%) children has platelets count less than 150000 and 16(24.6%) had C - reactive protein Positive .Mean duration of hospital stay 8 days (Range 1 -44 days), 20( 30.8% ) needed oxygen , 20(30.8%) needed Pediatric intensive care unit (PICU)admission and 6 (9.2%), needed ventilator. Forty seven (72.3%) recovered and discharged with death of 6.2% (n=4). Fifty six children (75.4%) has not experienced any problem after COVID -19 and only 2 children needed hospital admission in 90 days telephone follow up., Conclusions: In the first wave of the pandemic, Respiratory and Gastrointestinal symptoms were common presentation with few Severe and critical cases. Majority had good outcome. Majority has no other related illness till 90 days after discharge.

There are more than 170 million confirmed cases of COVID-19 worldwide, yet its effects on the endocrine system remain under-reported due to lack of awareness by the public, primary care givers and specialists. This is a narrative review using up-to-date literature discussing the consequences that infection with SARS-CoV-2 can have on diabetes and the endocrine glands including the adrenals, thyroid and pituitary, as well as hyponatremia and hypogonadism. Endocrinologists, internists and primary care physicians need to be aware of the involvement of the endocrine organs when dealing with people recovering from COVID-19 and actively manage any complications to reduce mortality and improve the quality of life of those affected., (© Royal College of Physicians 2021. All rights reserved.)

The COVID-19 pandemic is revealing growing reports of atypical presentation of the disease beyond the respiratory system. SARS-CoV-2 infection has been linked to multisystem vasculopathy including cardiopulmonary, cerebral and renal vasculature, potentially brought on by a dysregulated host immune response in a probable setting of a cytokine storm. Here, we describe a case of a previously healthy and active 74-year-old man presenting with acute cognitive decline with preceding non-specific influenza-like symptoms. He was then diagnosed with cerebral amyloid angiopathy (CAA)-associated intracerebral haemorrhage and was found to be COVID-19 positive. COVID-19-induced immune response may have further compromised the cerebral vessels already weakened by CAA, triggering multiple microhaemorrhages leading to clinical presentation. The limited evidence about the heterogeneity of COVID-19 manifestations suggests that clinicians should be aware and screen for concurrent COVID-19 in patients presenting with neurological features during the peak of this pandemic, as this offers the best chance for better clinical outcome., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: During the COVID-19 pandemic, Americans have increasingly relied on internet versus television news. The extent to which this change in health news consumption practice impacts health knowledge is not known. This study investigates the relationship between most trusted information source and COVID-19 knowledge., Methods: A cross-sectional online survey was sent to a convenience sample from a list of adults on a central Pennsylvania health system's marketing database 25-31 March 2020. Respondents were grouped by their trusted news sources and comparison of respondent COVID-19 knowledge was made between these groups for 5948 respondents., Results: Those who selected government health websites as their most trusted source were more likely to answer COVID-19 questions correctly than those who selected other internet news sources or television news (OR 1.21, p < .05; 1.08, p > .05; and 0.87, p < .05, respectively). Those who used Facebook as an additional source of news in any way were less likely to answer COVID-19 questions correctly than those who did not (OR 0.93, p  < .05)., Conclusions: COVID-19 knowledge correlates with trusted news source. To increase public knowledge of COVID-19 in order to maximize information dissemination and compliance with COVID-19-related public health recommendations, those who provide health information should consider use of the public's most trusted sources of information, as well as monitoring and correcting misinformation presented by other sources. Independent content review for accuracy in media may be warranted in public health emergencies to improve knowledge.