Occupational stress of elementary school teachers after eased COVID-19 restrictions: a qualitative study from China.

Background: On December 7, 2022, China optimized its virus response and significantly shifted its epidemic policy by downgrading COVID management and gradually restoring offline teaching in schools. This shift has brought many impacts on teachers. Aims: Through qualitative research of thematic analysis, this paper studies the occupational pressure of primary school teachers in China after the shift in epidemic policy. Methods: Two recruitment methods are adopted for this study. One was to email the principals of several primary schools in Zhejiang Province to introduce the research project and indicate the idea of recruiting participants. With their help, we have found teachers who volunteer to participate. The second was to release recruitment information in the network forum (e.g., online teacher forums) to find volunteer participants. Through semi-structured interviews and diaries, 18 primary school teachers from different regions and schools in Zhejiang Province were interviewed. All responses in the interviews were transcribed anonymously. Braun and Clarke's thematic analysis was used to analyze the participants' responses. Results: Eighteen participants took part in the research project. Forty-five final codes, generated from 89 codes initially obtained from the dataset, are classified into five final themes: uncertainty, overburdened, neglected, worry about students, and influence, which reflect the professional stress of primary school teachers following the epidemic prevention policies relaxed. Conclusion: Five themes were identified in the research. The problems described by the participants include burdensome offline activities, being disturbed out of hours, and appearing understaffed for the infection. These problems harmed the participants' mental health, including anxiety, fatigue, stress, and other adverse psychological conditions. Awareness and attention to the psychological situation of primary school teachers after the eased COVID control are crucial. We believe protecting teachers' mental health is necessary, especially in this particular period.

Comorbid asthma decreased the risk for COVID-19 mortality in the United Kingdom: Evidence based on a meta-analysis.

The study aimed to investigate the influence of comorbid asthma on the risk for mortality among patients with coronavirus disease 2019 (COVID-19) in the United Kingdom (UK) by utilizing a quantitative meta-analysis. The pooled odds ratio (OR) with 95% confidence interval (CI) was estimated by conducting a random-effects model. Sensitivity analysis, I2 statistic, meta-regression, subgroup analysis, Begg's analysis and Egger's analysis were all implemented. Our results presented that comorbid asthma was significantly related to a decreased risk for COVID-19 mortality in the UK based on 24 eligible studies with 1,209,675 COVID-19 patients (pooled OR = 0.81, 95% CI: 0.71-0.93; I2 = 89.2%, P < 0.01). Coming through further meta-regression to seek the possible cause of heterogeneity, none of elements might be responsible for heterogeneity. A sensitivity analysis proved the stability and reliability of the overall results. Both Begg's analysis (P = 1.000) and Egger's analysis (P = 0.271) manifested that publication bias did not exist. In conclusion, our data demonstrated that COVID-19 patients with comorbid asthma might bear a lower risk for mortality in the UK. Furthermore, routine intervention and treatment of asthma patients with severe acute respiratory syndrome coronavirus 2 infection should be continued in the UK.

Innate and Adaptive Immune Responses Induced by Aspergillus fumigatus Conidia and Hyphae.

Previous research indicated that hyphae of Aspergillus fumigatus (A. fumigatus) rather than conidia could successfully build a pulmonary aspergillosis model in immunocompetent mice. In this study, we compared the immune responses induced by hyphae and conidia to explore the possible mechanism of this striking phenomenon. Herein, a novel method was designed and adopted to quantify hyphal fragments. Murine macrophages RAW264.7 and human peripheral blood mononuclear cells were stimulated by A. fumigatus hyphae and conidia in vitro, respectively, and then immunological reactions were measured. Male C57BL/6 mice were challenged with conidia and hyphae through intratracheal inoculation. Dynamic conditions of mice were recorded, and RNA-seq measured corresponding immune responses. The results of the study confirmed that hyphae could induce more intensive inflammation than conidia in vitro and in vivo. However, macrophages revealed a higher production of ROS and M1 polarisation in response to conidia stimuli. Additionally, conidia could promote Th1 cell differentiation, while hyphae could increase the CD4/CD8 ratio. RNA-seq validated the fact that those multiple immunologically relevant pathways were more strongly activated by hyphae than conidia, which also promoted Th2 cell differentiation and suppressed Th1 signalling. Both hyphae and conidia could activate Th17 signalling. In general, conidia and hyphae induced distinctly different host immune responses, and the immune responses induced by conidia played a better protective effect. Therefore, the unique function of hyphae in the spread and infection of Aspergillus should be emphasised, and more research is required to clarify the underlying mechanisms for better understanding and management of aspergillosis.

Data-driven analysis to understand long COVID using electronic health records from the RECOVER initiative.

Recent studies have investigated post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID) using real-world patient data such as electronic health records (EHR). Prior studies have typically been conducted on patient cohorts with specific patient populations which makes their generalizability unclear. This study aims to characterize PASC using the EHR data warehouses from two large Patient-Centered Clinical Research Networks (PCORnet), INSIGHT and OneFlorida+, which include 11 million patients in New York City (NYC) area and 16.8 million patients in Florida respectively. With a high-throughput screening pipeline based on propensity score and inverse probability of treatment weighting, we identified a broad list of diagnoses and medications which exhibited significantly higher incidence risk for patients 30-180 days after the laboratory-confirmed SARS-CoV-2 infection compared to non-infected patients. We identified more PASC diagnoses in NYC than in Florida regarding our screening criteria, and conditions including dementia, hair loss, pressure ulcers, pulmonary fibrosis, dyspnea, pulmonary embolism, chest pain, abnormal heartbeat, malaise, and fatigue, were replicated across both cohorts. Our analyses highlight potentially heterogeneous risks of PASC in different populations.

BBIBP-CorV vaccination accelerates anti-viral antibody responses in heterologous Omicron infection: A retrospective observation study in Shanghai.

OBJECTIVES: To investigate how BBIBP-CorV vaccination affecting antibody responses upon heterologous Omicron infection. METHODS: 440 Omicron-infected patients were recruited in this study. Antibodies targeting SARS-CoV-2 spike protein receptor binding domain (RBD) and nucleoprotein of both wild-type (WT) and Omicron were detected by ELISA. The clinical relevance was further analyzed. RESULTS: BBIBP-CorV vaccinated patients exhibited higher anti-RBD IgG levels targeting both WT and Omicron than non-vaccinated patients at different stages. By using a 3-day moving average analysis, we found that BBIBP-CorV vaccinated patients exhibited the increases in both anti-WT and Omicron RBD IgG from the onset and reached the plateau at Day 8 whereas those in non-vaccinated patients remained low during the disease. Significant increase in anti-WT RBD IgA was observed only in vaccinated patients. anti-Omicron RBD IgA levels remained low in both vaccinated and non-vaccinated patients. Clinically, severe COVID-19 only occurred in non-vaccinated group. anti-RBD IgG and IgA targeting both WT and Omicron were negatively correlated with virus load, hospitalization days and virus elimination in vaccinated patients. CONCLUSIONS: BBIBP-CorV vaccination effectively reduces the severity of Omicron infected patients. The existence of humoral memory responses established through BBIBP-CorV vaccination facilitates to induce rapid recall antibody responses when encountering SARS-CoV-2 variant infection.

Recent progress in polymeric gene vectors: Delivery mechanisms, molecular designs, and applications.

Gene therapy and gene delivery have drawn extensive attention in recent years especially when the COVID-19 mRNA vaccines were developed to prevent severe symptoms caused by the corona virus. Delivering genes, such as DNA and RNA into cells, is the crucial step for successful gene therapy and remains a bottleneck. To address this issue, vehicles (vectors) that can load and deliver genes into cells are developed, including viral and non-viral vectors. Although viral gene vectors have considerable transfection efficiency and lipid-based gene vectors become popular since the application of COVID-19 vaccines, their potential issues including immunologic and biological safety concerns limited their applications. Alternatively, polymeric gene vectors are safer, cheaper, and more versatile compared to viral and lipid-based vectors. In recent years, various polymeric gene vectors with well-designed molecules were developed, achieving either high transfection efficiency or showing advantages in certain applications. In this review, we summarize the recent progress in polymeric gene vectors including the transfection mechanisms, molecular designs, and biomedical applications. Commercially available polymeric gene vectors/reagents are also introduced. Researchers in this field have never stopped seeking safe and efficient polymeric gene vectors via rational molecular designs and biomedical evaluations. The achievements in recent years have significantly accelerated the progress of polymeric gene vectors toward clinical applications.

Recent advances in cell-based and cell-free therapeutic approaches for sarcopenia.

Sarcopenia is a progressive loss of muscle mass and function that is connected with increased hospital expenditures, falls, fractures, and mortality. Although muscle loss has been related to aging, injury, hormonal imbalances, and diseases such as malignancies, chronic obstructive pulmonary disease, heart failure, and kidney failure, the underlying pathogenic mechanisms of sarcopenia are unclear. Exercise-based interventions and multimodal strategies are currently being considered as potential therapeutic approaches to prevent or treat these diseases. Although drug therapy research is ongoing, no drug has yet been proven to have a substantial safety and clinical value to be the first drug therapy to be licensed for sarcopenia. To better understand the molecular alterations underlying sarcopenia and effective treatments, we review leading research and available findings from the systemic change to the muscle-specific microenvironment. Furthermore, we explore possible mechanisms of sarcopenia and provide new knowledge for the development of novel cell-free and cell-based therapeutics. This review will assist researchers in developing better therapies to improve muscle health in the elderly.

The pandemic and changes in early career researchers' career prospects, research and publishing practices.

INTRODUCTION: As part of the Harbnger-2 project, this study aimed to discover the impact of the COVID-19 pandemic on junior researchers' work-life, career prospects, research and publishing practices and networking. METHODS: An online international survey of 800 early career researchers (ECRs) was conducted in 2022. A questionnaire was developed based on three rounds of interviews and distributed using multiple channels including publishers, social media, and direct email to ECRs. RESULTS: The impact of the pandemic on career prospects, morale, job security, productivity, ability to network and collaborate, and quality and speed of peer review has on the whole been more negative than positive. A quarter of ECRs shifted their research focus to pandemic-related topics and half of those who did, benefited largely due to increased productivity and impact. The majority worked remotely/from home and more than two-thirds of those who did so benefitted from it. While virtual or hybrid conferences have been embraced by the majority of ECRs, around a third still preferred face-to-face only conferences. The use of library online platforms, Sci-Hub, ResearchGate, Google Scholar and smartphone to search and access full-text papers increased. ECRs prioritised journals with fast submission procedures for the publishing of their papers and spent more time on increasing the visibility of their research. Fees were a problem for publishing open access. CONCLUSION: Although, generally, the pandemic negatively impacted many aspects of ECRs' work-life, certain research areas and individuals benefited from being more appreciated and valued, and, in some cases, resulted in increased resources, better productivity and greater impact. Changes, such as the use of digital technologies and remote working created new opportunities for some ECRs. While continuing work flexibility and hybrid conferences might benefit some ECRs, institutions should also take measures to help those ECRs whose career and productivity have been adversely impacted.

Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2.

Background: This study explores the risk factors associated with viral shedding time in elderly Chinese patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron. Methods: Participants infected with SARS-CoV-2 omicron were enrolled in a retrospective study, and divided into two groups according to shedding time (≥10 days, "late clearance group" and <10 days, "early clearance group"). Results: A total of 180 patients were enrolled in the study (88 early, 92 late), with a median viral shedding time of 10 days and a mean age of 77.02 years. Prolonged SARS-CoV-2 omicron shedding was associated with old age (p = 0.007), lack of vaccination (p = 0.001), delayed admission to hospital after onset of diagnosis (p = 0.001), D-dimer (p = 0.003), and methylprednisolone treatment (p = 0.048). In multivariate analysis, vaccination (OR, 0.319, 95% CI, 0.130-0.786, p = 0.013), Paxlovid (OR, 0.259, 95% CI, 0.104-0.643, p = 0.004), and time from onset of diagnosis to admission (OR, 1.802, 95% CI, 1.391-2.355, p = 0.000) were significantly associated with viral clearance. Conclusions: Time from onset of diagnosis to hospitalization, lack of treatment with Paxlovid, and lack of vaccination were independent risk factors in elderly Chinese patients infected with SARS-CoV-2 omicron for prolonged viral shedding.

Identifying environmental risk factors for post-acute sequelae of SARS-CoV-2 infection: An EHR-based cohort study from the recover program.

Post-acute sequelae of SARS-CoV-2 infection (PASC) affects a wide range of organ systems among a large proportion of patients with SARS-CoV-2 infection. Although studies have identified a broad set of patient-level risk factors for PASC, little is known about the association between "exposome"-the totality of environmental exposures and the risk of PASC. Using electronic health data of patients with COVID-19 from two large clinical research networks in New York City and Florida, we identified environmental risk factors for 23 PASC symptoms and conditions from nearly 200 exposome factors. The three domains of exposome include natural environment, built environment, and social environment. We conducted a two-phase environment-wide association study. In Phase 1, we ran a mixed effects logistic regression with 5-digit ZIP Code tabulation area (ZCTA5) random intercepts for each PASC outcome and each exposome factor, adjusting for a comprehensive set of patient-level confounders. In Phase 2, we ran a mixed effects logistic regression for each PASC outcome including all significant (false positive discovery adjusted p-value < 0.05) exposome characteristics identified from Phase I and adjusting for confounders. We identified air toxicants (e.g., methyl methacrylate), particulate matter (PM2.5) compositions (e.g., ammonium), neighborhood deprivation, and built environment (e.g., food access) that were associated with increased risk of PASC conditions related to nervous, blood, circulatory, endocrine, and other organ systems. Specific environmental risk factors for each PASC condition and symptom were different across the New York City area and Florida. Future research is warranted to extend the analyses to other regions and examine more granular exposome characteristics to inform public health efforts to help patients recover from SARS-CoV-2 infection.

Data-driven identification of post-acute SARS-CoV-2 infection subphenotypes.

The post-acute sequelae of SARS-CoV-2 infection (PASC) refers to a broad spectrum of symptoms and signs that are persistent, exacerbated or newly incident in the period after acute SARS-CoV-2 infection. Most studies have examined these conditions individually without providing evidence on co-occurring conditions. In this study, we leveraged the electronic health record data of two large cohorts, INSIGHT and OneFlorida+, from the national Patient-Centered Clinical Research Network. We created a development cohort from INSIGHT and a validation cohort from OneFlorida+ including 20,881 and 13,724 patients, respectively, who were SARS-CoV-2 infected, and we investigated their newly incident diagnoses 30-180 days after a documented SARS-CoV-2 infection. Through machine learning analysis of over 137 symptoms and conditions, we identified four reproducible PASC subphenotypes, dominated by cardiac and renal (including 33.75% and 25.43% of the patients in the development and validation cohorts); respiratory, sleep and anxiety (32.75% and 38.48%); musculoskeletal and nervous system (23.37% and 23.35%); and digestive and respiratory system (10.14% and 12.74%) sequelae. These subphenotypes were associated with distinct patient demographics, underlying conditions before SARS-CoV-2 infection and acute infection phase severity. Our study provides insights into the heterogeneity of PASC and may inform stratified decision-making in the management of PASC conditions.

Factors associated with prolonged viral shedding in older patients infected with Omicron BA.2.2

Background This study explores the risk factors associated with viral shedding time in elderly Chinese patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron. Methods Participants infected with SARS-CoV-2 omicron were enrolled in a retrospective study, and divided into two groups according to shedding time (≥10 days, "late clearance group” and <10 days, "early clearance group”). Results A total of 180 patients were enrolled in the study (88 early, 92 late), with a median viral shedding time of 10 days and a mean age of 77.02 years. Prolonged SARS-CoV-2 omicron shedding was associated with old age (p = 0.007), lack of vaccination (p = 0.001), delayed admission to hospital after onset of diagnosis (p = 0.001), D-dimer (p = 0.003), and methylprednisolone treatment (p = 0.048). In multivariate analysis, vaccination (OR, 0.319, 95% CI, 0.130–0.786, p = 0.013), Paxlovid (OR, 0.259, 95% CI, 0.104–0.643, p = 0.004), and time from onset of diagnosis to admission (OR, 1.802, 95% CI, 1.391–2.355, p = 0.000) were significantly associated with viral clearance. Conclusions Time from onset of diagnosis to hospitalization, lack of treatment with Paxlovid, and lack of vaccination were independent risk factors in elderly Chinese patients infected with SARS-CoV-2 omicron for prolonged viral shedding.

A diagnostic model for serious COVID-19 infection among older adults in Shanghai during the Omicron wave.

Background: The Omicron variant is characterized by striking infectivity and antibody evasion. The analysis of Omicron variant BA.2 infection risk factors is limited among geriatric individuals and understanding these risk factors would promote improvement in the public health system and reduction in mortality. Therefore, our research investigated BA.2 infection risk factors for discriminating severe/critical from mild/moderate geriatric patients. Methods: Baseline characteristics of enrolled geriatric patients (aged over 60 years) with Omicron infections were analyzed. A logistic regression analysis was conducted to evaluate factors correlated with severe/critical patients. A receiver operating characteristic (ROC) curve was constructed for predicting variables to discriminate mild/moderate patients from severe/critical patients. Results: A total of 595 geriatric patients older than 60 years were enrolled in this study. Lymphocyte subset levels were significantly decreased, and white blood cells (WBCs) and D-dimer levels were significantly increased with disease progression from a mild/moderate state to a severe/critical state. Univariate and multivariate logistic regression analyses identified a panel of WBCs, CD4+ T cell, and D-dimer values that were correlated with good diagnostic accuracy for discriminating mild/moderate patients from severe/critical patients with an area under the curve of 0.962. Conclusion: Some key baseline laboratory indicators change with disease development. A panel was identified for discriminating mild/moderate patients from severe/critical patients, suggesting that the panel could serve as a potential biomarker to enable physicians to provide timely medical services in clinical practice.

Identification of CKD, bedridden history and cancer as higher-risk comorbidities and their impact on prognosis of hospitalized Omicron patients: a multi-centre cohort study.

To further describe the effect of the "fragile population" and their "higher-risk" comorbidities on prognosis among hospitalized Omicron patients, this observational cohort study enrolled hospitalized patients confirmed with SARS-CoV-2 during the 2022 Omicron wave in Shanghai, China. The primary outcome was progression to severe or critical cases. The secondary outcome was viral shedding time from the first positive SARS-CoV-2 detection. A total of 847 participants were enrolled, most of whom featured as advanced age (>70 years old: 30.34%), not fully vaccinated (55.84%), combined with at least 1 comorbidity (65.41%). Multivariate cox regression suggested age >70 years old (aHR[95%CI] 0.78[0.61-0.99]), chronic kidney disease (CKD) stage 4-5 (aHR[95%CI] 0.61[0.46-0.80]), heart conditions (aHR[95%CI] 0.76[0.60-0.97]) would elongate viral shedding time and fully/booster vaccination (aHR[95%CI] 1.4 [1.14-1.72]) would shorten this duration. Multivariate logistic regression suggested CKD stage 4-5 (aHR[95%CI] 3.21[1.45-7.27]), cancer (aHR[95%CI] 9.52[4.19-22.61]), and long-term bedridden status (aHR[95%CI] 4.94[2.36-10.44]) were the "higher" risk factor compared with the elderly, heart conditions, metabolic disorders, isolated hypertension, etc. for severity while female (aHR[95%CI] 0.34[0.16-0.68]) and fully/booster Vaccination (aHR[95%CI] 0.35[0.12-0.87]) could provide protection from illness progression. CKD stage 4-5, cancer and long-term bedridden history were "higher-risk" factors among hospitalized Omicron patients for severity progression while full vaccination could provide protection from illness progression.