B cell acute lymphoblastic leukemia following mild COVID-19 in an 11-year-old boy (preprint)

Coronavirus disease-2019 (COVID-19) has infected millions of people with high lethality in the world, but little is known whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has impacts on triggering pediatric acute lymphoblastic leukemia (ALL). We present a case of a child with atypical clinical manifestation who developed B-cell acute lymphoblastic leukemia following a mild symptomatic COVID-19 infection. This case underlines the risks of potential oncogenic effects with the history of this viral infection and a state of immunosuppression.

Humoral immune response to omicron infection in long-term Wuhan-Hu-1-imprinted population (preprint)

Recent WHO vaccination guidance no longer recommends COVID-19 vaccination beyond the first booster in low risk population, citing high population-level hybrid immunity due to widespread omicron infections.1 Although SARS-CoV-2 infection confers durable protection against reinfection,2-4 it may also produce immune imprinting, which skews subsequent immune response to variant antigens toward the first-exposed antigen based on the antigenic distance.5,6 China has the earliest and exclusively Wuhan-Hu-1(WH1)-imprinted population before the 2022 nation-wide omicron outbreak,7 which offers a unique opportunity to study long-term immune imprinting between most antigenically distant strains. Here, we assessed pseudovirus neutralization activity and anti-WH1 receptor binding domain (RBD) antibodies in 4 Chinese cohorts with hybrid or vaccine-only imprinting, or naïve to SARS-CoV-2 prior to omicron BF.7 infection. Both hybrid and vaccine-only imprinting augmented post-infection serum neutralization of WH1 and omicron sub-variants BF.7/BQ.1.1/XBB.1.5 comparing to naïve background. Feedback from pre-existing high-affinity antibodies limited the magnitude of humoral immune response to omicron infection without compromising protection, while antigenic seniority of pre-existing cross-reactive B cells only slightly reduces forward neutralization breadth in hybrid- and RBD vaccine-imprinted participants. Our results support the effectiveness of hybrid immunity against omicron reinfection in long-term imprinted population and provide immunological basis for similar epidemiological findings.8-10

The impact of the COVID-19 epidemic on tuberculosis control in China.

BACKGROUND: In response to the COVID-19 epidemic, China implemented a series of interventions that impacted tuberculosis (TB) control in the country. METHODS: Based on routine surveillance data and questionnaires, the study analyzed TB notification, follow-up examinations, and treatment outcomes. The data were split into three phases in relation to outbreak, lockdown and reopen when the nationwide COVID-19 response started in 2020: control (11 weeks prior), intensive (11 weeks during and immediately after), and regular (4 additional weeks). Data from 2017-2019 were used as baseline. FINDINGS: The notified number of TB patients decreased sharply in the 1st week of the intensive period but took significantly longer to rebound in 2020 compared with baseline. The percentages of TB patients undergoing sputum examination within one week after 2 months treatment and full treatment course in the intensive period were most affected and decreased by 8% in comparison with control period. 75•2% (221/294) of counties reallocated CDC and primary health care workers to fight the COVID-19 epidemic, 26•9% (725/2694) of TB patients had postponed or missed their follow-up examinations due to travel restrictions and fear of contracting COVID-19. INTERPRETATION: In the short term, the COVID-19 epidemic mostly affected TB notification and follow-up examinations in China, which may lead to a surge of demand for TB services in the near future. To cope with this future challenge, an emergency response mechanism for TB should be established. FUNDING: National Health Commission of China-Bill & Melinda Gates Foundation TB Collaboration project (OPP1137180).

Prevalence of grief symptoms and disorders in the time of COVID-19 pandemic: A meta-analysis.

Millions of people worldwide are mourning the loss of loved ones due to the COVID-19 epidemic, which may adversely impact their mental health. This meta-analysis aimed to investigate pandemic grief symptoms and disorders for developing policy, practice, and research priorities. The databases of Cochrane, Embase, Ovid-MEDLINE, WHO COVID-19, NCBI SARS-CoV-2, Scopus, Web of Science, CINAHL, and Science Direct were comprehensively searched until July 31, 2022. The Joanna Briggs Institute's and Hoy's criteria were used to evaluate the studies. A pooled prevalence was presented in a forest plot figure with a corresponding 95% confidence interval (CI) and prediction interval. Between-study heterogeneity was measured using the I2 and Q statistics. Variations in the prevalence estimates in different subgroups were examined by moderator meta-analysis. The search identified 3677 citations, of which 15 studies involving 9289 participants were included in the meta-analysis. The pooled prevalence rate of grief symptoms was 45.1% (95%CI: 32.6%-57.5%), and grief disorder was 46.4% (95%CI: 37.4%-55.5%). Grief symptoms were significantly higher in <6 months (45.8%; 95%CI: 26.3%-65.3%) compared to the period of more than 6 months. Unfortunately, moderator analyses for grief disorders could not be performed due to limited studies. The prevalence of grief problems during the pandemic was substantially higher than in non-pandemic conditions; therefore, it is crucial to strengthen bereavement support to reduce psychological distress. The results provide a foundation for nurses and healthcare workers to anticipate a heightened need for support and provision of bereavement care in the post-pandemic era.

Effectiveness of respiratory rehabilitation in patients with COVID-19: A meta-analysis.

AIM: Examine effectiveness of respiratory rehabilitation and moderating factors on lung function and exercise capacity in post-COVID-19 patients. DESIGN: Meta-analysis. METHODS: R software 4.0.2 assessed the effectiveness of respiratory rehabilitation adopting the random-effects model and presenting standardised mean differences (SMDs). Heterogeneity was determined by Cochran's Q and I2 . The Cochrane Risk of Bias 2.0 and MINORS evaluated quality of the included studies. DATA SOURCES: A comprehensive search was undertaken in Cochrane, Embase, Ovid-MEDLINE, Scopus, NCBI SARS-CoV-2 Resources, ProQuest, Web of Science and CINAHL until March 2022. RESULTS: Of the 5703 identified studies, 12 articles with 596 post-COVID-19 patients were included. Eleven of our twelve studies had moderate to high quality and one study had high risk of bias assessed with MINORS and RoB 2 tool. Overall, respiratory rehabilitation was effective in improving forced expiratory volume in 1 s (1.14; 95%CI 0.39-1.18), forced vital capacity (0.98; 95%CI 0.39-1.56), total lung capacity (0.83; 95%CI 0.22-1.44), 6-minute walk distance (1.56; 95%CI 1.10-2.02) and quality of life (0.99; 95%CI 0.38-1.60). However, no significant differences were observed for ratio of the forced expiratory volume in 1 s to the forced vital capacity of the lungs, anxiety and depression. Respiratory rehabilitation for post-COVID-19 patients was effective in those without comorbidities, performed four types of exercise programs, frequency ≥3 times/week and rehabilitation time 6 weeks. CONCLUSIONS: Respiratory rehabilitation improved lung function, exercise capacity and quality of life in post-COVID-19 patients. The findings suggest rehabilitation programs for post-COVID-19 patients should use multiple respiratory exercise programs with frequency of ≥3 times per week for longer than 6 weeks. IMPACT: These findings will help improve the implementation of respiratory rehabilitation programs for post-COVID-19 patients. IMPLICATIONS FOR THE PROFESSION: Our findings can be used to develop patient-centred respiratory rehabilitation interventions by nurses and clinicians for post-COVID-19 patients. REPORTING METHOD: PRISMA guideline was followed. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Global prevalence of low resilience among the general population and health professionals during the COVID-19 pandemic: A meta-analysis.

OBJECTIVE: To estimate the global prevalence of low resilience among the general population and health professionals during the COVID-19 pandemic. METHODS: Embase, Ovid-MEDLINE, PubMed, Scopus, Web of Science, CINAHL, WHO COVID-19 databases, and grey literature were searched for studies from January 1, 2020, to August 22, 2022. Hoy's assessment tool was used to assess for risk of bias. Meta-analysis and moderator analysis was performed using the Generalized Linear Mixed Model with a corresponding 95 % confidence interval (95 % CI) adopting the random-effect model in R software. Between-study heterogeneity was measured using I2 and τ2 statistics. RESULTS: Overall, 44 studies involving 51,119 participants were identified. The pooled prevalence of low resilience was 27.0 % (95 % CI: 21.0 %-33.0 %) with prevalence among the general population being 35.0 % (95 % CI: 28.0 %-42.0 %) followed by 23.0 % (95 % CI: 16.0 %-30.9 %) for health professionals. The 3-month trend analysis of the prevalence of low resilience beginning January 2020 to June 2021 revealed upward then downward patterns among overall populations. The prevalence of low resilience was higher in females, studied during the delta variant dominant period, frontline health professionals, and undergraduate degree education. LIMITATIONS: Study outcomes showed high heterogeneity; however, sub-group and meta-regression analyses were conducted to identify potential moderating factors. CONCLUSIONS: Globally, 1 out of 4 people among the general population and health professionals experienced low resilience due to COVID-19 adversity. The prevalence of low resilience was twice as much among the general population compared to health professionals. These findings provide information for policymakers and clinicians in the development and implementation of resilience-enhancing programs.

Inhibition mechanism and antiviral activity of an α-ketoamide based SARS-CoV-2 main protease inhibitor (preprint)

SARS-CoV-2 has demonstrated extraordinary ability to evade antibody immunity by antigenic drift. Small molecule drugs may provide effective therapy while being part of a solution to circumvent SARS-CoV-2 immune escape. In this study we report an alpha-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease (Mpro), RAY1216. Enzyme inhibition kinetic analysis established that RAY1216 is a slow-tight inhibitor with a Ki of 8.6 nM; RAY1216 has a drug-target residence time of 104 min compared to 9 min of PF-07321332 (nirmatrelvir), the antiviral component in Paxlovid, suggesting that RAY1216 is approximately 12 times slower to dissociate from the protease-inhibitor complex compared to PF-07321332. Crystal structure of SARS-CoV-2 Mpro:RAY1216 complex demonstrates that RAY1216 is covalently attached to the catalytic Cys145 through the alpha-ketoamide warhead; more extensive interactions are identified between bound RAY1216 and Mpro active site compared to PF-07321332, consistent with a more stable acyl-enzyme inhibition complex for RAY1216. In cell culture and human ACE2 transgenic mouse models, RAY1216 demonstrates comparable antiviral activities towards different SARS-CoV-2 virus variants compared to PF-07321332. Improvement in pharmacokinetics has been observed for RAY1216 over PF-07321332 in various animal models, which may allow RAY1216 to be used without ritonavir. RAY1216 is currently undergoing phase III clinical trials (https://clinicaltrials.gov/ct2/show/NCT05620160) to test real-world therapeutic efficacy against COVID-19.

Comparison of perceived general health status between suspected and confirmed cases of COVID-19 and identifying the nursing diagnoses: A cross-sectional study.

AIM: This study aimed to examine the differences in health status between patients with confirmed COVID-19 and those suspected (other diagnosis) and to identify nursing diagnoses using a structured checklist from a hospital in China. DESIGN: Cross-sectional study design was used. METHODS: One hundred sixty COVID-19 confirmed, and suspected patients were conveniently selected. A structured survey and checklist were utilized. Independent t test and chi-square test were employed to compare the mean between patients with confirmed coronavirus infection and others. A two-sided p-value of .05 or less is considered statistically significant. RESULTS: The study yielded a response rate of 93.6%. The result indicated that patients with confirmed coronavirus infection have a higher proportion of perceived General Health Status than inpatients with suspected (other) diagnoses. The finding also indicated that ineffective airway clearance, hyperthermia, imbalanced nutrition less than body requirement and sleep pattern disturbance were the main nursing diagnoses identified.

IL-4 receptor blockade is a global repressor of naïve B cell development and responses in a dupilumab-treated patient.

Here, we report a case of atopic dermatitis (AD) in a patient who received biweekly doses of dupilumab, an antibody against the IL-4 receptor α chain (IL-4Rα). Single cell RNA-sequencing showed that naïve B cells expressed the highest levels of IL4R compared to other B cell subpopulations. Compared to controls, the dupilumab-treated patient exhibited diminished percentages of IL4R+IGHD+ naïve B cells and down-regulation of IL4R, FCER2 (CD23), and IGHD. Dupilumab treatment resulted in upregulation of genes associated with apoptosis and inhibition of B cell receptor signaling and down-regulation of class-switch and memory B cell development genes. The dupilumab-treated patient exhibited a rapid decline in COVID-19 anti-spike and anti-receptor binding domain antibodies between 4 and 8 and 11 months post COVID-19 vaccination. Our data suggest that intact and persistent IL-4 signaling is necessary for maintaining robust survival and development of naïve B cells, and maintaining a long term vaccine response.

Nanoformulations targeting immune cells for cancer therapy: mRNA therapeutics

The approved worldwide use of two messenger RNA (mRNA) vaccines (BNT162b2 and mRNA-1273) in late 2020 has proven the remarkable success of mRNA therapeutics together with lipid nanoformulation technology in protecting people against coronaviruses during COVID-19 pandemic. This unprecedented and exciting dual strategy with nanoformulations and mRNA therapeutics in play is believed to be a promising paradigm in targeted cancer immunotherapy in future. Recent advances in nanoformulation technologies play a prominent role in adapting mRNA platform in cancer treatment. In this review, we introduce the biologic principles and advancements of mRNA technology, and chemistry fundamentals of intriguing mRNA delivery nanoformulations. We discuss the latest promising nano-mRNA therapeutics for enhanced cancer immunotherapy by modulation of targeted specific subtypes of immune cells, such as dendritic cells (DCs) at peripheral lymphoid organs for initiating mRNA cancer vaccine-mediated antigen specific immunotherapy, and DCs, natural killer (NK) cells, cytotoxic T cells, or multiple immunosuppressive immune cells at tumor microenvironment (TME) for reversing immune evasion. We highlight the clinical progress of advanced nano-mRNA therapeutics in targeted cancer therapy and provide our perspectives on future directions of this transformative integrated technology toward clinical implementation.

Analysis of mental health status and influencing factors of medical staff during static management of the COVID-19 epidemic: a cross-sectional study (preprint)

Objective To assess the mental health of medical staff as the COVID-19 pandemic is being managed statically.Methods By a convenience sampling method, 560 medical personnel who worked in a certain region of China throughout the static management period were chosen as the research objects. To obtain information, the basic data questionnaire, the COVID-19 epidemic perception questionnaire, the psychological questionnaire for public health emergencies, the psychological resilience scale, and the social support scale were all implemented.Results The psychological questionnaire for public health emergencies of medical staff had a total score of 2.03 (0.87, 2.77), with scores for each dimension of depression, neurasthenia, fear, anxiety, and hypochondriasis being 0.56 (0,0.833), 0.425 (0.2,0.6), 0.57 (0.17,0.83), and 0.207 (0,0.4), respectively. Multivariate linear regression analysis demonstrated that monthly salary, whether there was physical disease in the past, apartment, whether to work in the isolation area, attitude toward static management, psychological resilience score, social support score, and emotional knowledge score entered the influencing factor model of mental health of medical personnel (F = 4.759, P < 0.001), which could independently explain 33.8% of the total variation.Conclusion With static administration, the level of psychological stress experienced by medical workers during public health emergencies is excessive. To safeguard the physical and emotional health of medical workers, managers should improve the management of public health emergencies, establish a scientific and coordinated training program, and provide psychological assistance in a timely manner.

Advantages and challenges of fostering cognitive integration through virtual collaborative learning: a qualitative study.

BACKGROUND: The drastic shift from face-to-face classes to online learning due to the COVID-19 pandemic has enabled educators to ensure the continuity of learning for health professions students in higher education. Collaborative learning, a pedagogy used to facilitate knowledge integration by helping students translate theory from basic sciences to clinical application and practice, has thus been transformed from a face-to-face to a virtual strategy to achieve the learning objectives of a multi-disciplinary and integrated module. OBJECTIVES: This study aimed to describe and evaluate, through focus group discussions, a virtual collaborative learning activity implemented to assist first year undergraduate nursing students to develop cognitive integration in a module consisting of pathophysiology, pharmacology, and nursing practice. METHODS: Fourteen first year undergraduate students and four faculty involved in facilitating the virtual collaboration participated in the study. Focus group discussions were conducted to elicit the perceptions of students and staff on the virtual collaborative learning session conducted at the end of the semester. RESULTS: Three themes were generated from the thematic analysis of the students' focus group scripts. These were: (1) achieving engagement and interaction, (2) supporting the collaborative process, and (3) considering practical nuances. The three themes were further subdivided into subthemes to highlight noteworthy elements captured during focus group discussions. Three themes also emerged from the focus group discussion scripts of faculty participants: (1) learning to effectively manage, (2) facing engagement constraints, and (3) achieving integration. These themes were further sectioned into salient subthemes. CONCLUSION: The virtual collaborative learning pedagogy is valuable in fostering cognitive integration. However, meticulous planning considering various variables prior to implementation is needed. With better planning directed at addressing the learners' needs and the faculty's capabilities and readiness for online learning pedagogies, and with a strong institutional support to help mitigate the identified constraints of virtual collaborative learning, students and faculty will benefit.

The short-term impact of meteorological factors on the transmission of COVID-19 in Guangzhou

Objective: To investigate the effect of meteorological factors on the transmission of corolla virus disease 2019 (COVID-19).

Cross-Sectional Analysis of Taiwanese Pharmacy Students' Experiences and Perceptions of Transitioning from In-Hospital Internships to Distance Learning Due to COVID-19.

The introductory pharmacy practice experiences (IPPE) in Taiwan, which are traditionally conducted in physical hospital settings, incorporated up to 30% distance learning from May 2021 due to Coronavirus Disease 2019 (COVID-19). A web-based cross-sectional survey was adopted to investigate pharmacy students' experiences and perceptions of transitioning from in-hospital internships to distance learning due to COVID-19 in the pharmacy department of a university in Southern Taiwan. We analyzed the results to discover factors that significantly affected students' perceptions of transitioning from in-hospital internships to distance learning. In total, 81 interns from the university's pharmacy department responded to the questionnaire. Approximately half of the participants felt happy when they learned, before the internship began, that the internship would be partially replaced with distance learning. The overall satisfaction rate was 67.9%, and no significant differences was observed in students' satisfaction between hospital size or distance-learning time. However, more students in the medical center felt they had insufficient time to finish assignments compared to those in the regional hospitals, and the students who had 11-15 days of distance learning felt that they interacted more smoothly with their peers compared to those who had other durations. Program designers should make distance internship courses more student-centered, with a focus on increasing interactions between students, teachers, and peers to compensate for the lack of physical presence.

Digital Interpretation as a Bridge to Support the Sense of Place: “Lord Guan Online!” DaxiDaxi Website

In the context of coronavirus (COVID-19) pandemic, large-scale events have been forced to stop as well as movement of people between cities. At Daxi in Taoyuan, Taiwan, there is an event that lasts for over a century, Puji Temple Annual Celebration of Saintly Emperor Guan’s Birthday, held every summer on June 24 of the lunar calendar. It is not only registered as Taoyuan City’s intangible cultural heritage but also considered as the second Chinese New Year for local people. In order to express gratitude to Saintly Emperor Guan for his blessing, the local groups ‘She-Tou’, residents, shopkeepers and volunteers make a great effort on the preparations before the celebration. Local people who at the time do not live in Daxi because they are studying, working or after marriage are living in other cities would also come back to the town on this day. This traditional and cultural event bred from belief has become a mechanism of community cohesion and has shaped Daxi’s unique sense of place. Unfortunately, the traditional pilgrimage of the celebration in 2021 has been paused due to the pandemic situation. However, thanks to the long-term collaboration and participation of the local museum, the ritual of faith can continue in a new way. This article takes the DaxiDaxi “Lord Guan Online” website and its Facebook page as an example. By analysing how the Daxi Wood Art Ecomuseum interprets the traditional celebration and its culture in a digital way, we try to explore the possibility of digital tools as a powerful medium for connecting people and people and place during the pandemic period.

Response time analysis of a manufacturing supply chain with performance evaluation process algebra

The supply and demand shocks brought on by the Covid-19 crisis are forcing manufacturers everywhere to reassess or even reorganise their supply chains. This paper proposes a general framework that can achieve fast compositional modelling with stochastic performance evaluation process algebra (PEPA) for supply chain systems. The key feature of such a framework is the PEPA-based quantitative analysis approach which includes a new method for calculating response time based on compositional PEPA models. The framework aims to provide an efficient modelling prototype for supply chain systems while supporting accurate response time-based quantitative analysis. To our knowledge, this is the first work using process algebra-based compositional modelling to quantitatively analyse supply chain systems.

Rapid Control of a SARS-CoV-2 B.1.617.2 (Delta) Variant COVID-19 Community Outbreak: The Successful Experience in Pingtung County of Taiwan.

The Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2) was an outbreak in December, 2019 and rapidly spread to the world. All variants of SARS-CoV-2, including the globally and currently dominant Delta variant (Delta-SARS-CoV-2), caused severe disease and mortality. Among all variants, Delta-SARS-CoV-2 had the highest transmissibility, growth rate, and secondary attack rate than other variants except for the new variant of Omicron that still exists with many unknown effects. In Taiwan, the pandemic Delta-SARS-CoV-2 began in Pingtung from 14 June 2021 and ceased at 11 July 2021. Seventeen patients were infected by Delta-SARS-CoV-2 and 1 person died during the Pingtung outbreak. The Public Health Bureau of Pingtung County Government stopped the Delta-SARS-CoV-2 outbreak within 1 month through measures such as epidemic investigation, rapid gene sequencing, rapidly expanding isolation, expanded screening of the Delta-SARS-CoV-2 antigen for people who lived in regional villages, and indirect intervention, including rapid vaccination, short lockdown period, and travel restrictions. Indirect environmental factors, such as low levels of air pollution, tropic weather in the summer season, and rural areas might have accelerated the ability to control the Delta-SARS-CoV-2 spread. This successful experience might be recommended as a successful formula for the unvaccinated or insufficiently vaccinated regions.

The COVID-19 pandemic: Narratives of front-line nurses from Wuhan, China.

This study aimed to explore the experiences of nurses in Wuhan Hospital as front-line workers during the COVID-19 pandemic. A descriptive qualitative study of such nurses was conducted from a tertiary hospital in Wuhan. Semi-structured individual interviews were undertaken with 8 registered nurses who were front-line health workers in one of the COVID-19 wards and 3 nursing managers from the response team. Five discrete themes were identified from the narratives of nurses' experiences during the COVID-19 outbreak in Wuhan: "content of fundamental care," "teamwork," "reciprocity," "nurses' own worries," and "lifelong learning and insights." Nurses in the front line of care during the COVID-19 pandemic can contribute important information from their hands-on experience for providing a holistic response to an infectious outbreak like COVID-19. The concerns nurses raised at both personal and professional levels have implications for nursing education and clinical practice settings, particularly in the time of a pandemic when nurses' well-being requires attention, and at the same time for considering organizational factors that enable nurses to provide care to patients with confidence. Hospital policies and nursing management need to be ready and adhere to flexible work planning systems and approaches during a pandemic.

Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants.

Glycan-masking the vaccine antigen by mutating the undesired antigenic sites with an additional N-linked glycosylation motif can refocus B-cell responses to desired epitopes, without affecting the antigen's overall-folded structure. This study examined the impact of glycan-masking mutants of the N-terminal domain (NTD) and receptor-binding domain (RBD) of SARS-CoV-2, and found that the antigenic design of the S protein increases the neutralizing antibody titers against the Wuhan-Hu-1 ancestral strain and the recently emerged SARS-CoV-2 variants Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). Our results demonstrated that the use of glycan-masking Ad-S-R158N/Y160T in the NTD elicited a 2.8-fold, 6.5-fold, and 4.6-fold increase in the IC-50 NT titer against the Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2) variants, respectively. Glycan-masking of Ad-S-D428N in the RBD resulted in a 3.0-fold and 2.0-fold increase in the IC-50 neutralization titer against the Alpha (B.1.1.7) and Beta (B.1.351) variants, respectively. The use of glycan-masking in Ad-S-R158N/Y160T and Ad-S-D428N antigen design may help develop universal COVID-19 vaccines against current and future emerging SARS-CoV-2 variants.