SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids (preprint)

SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.

Changes in primary healthcare workforce burnout during and after the termination of COVID-19 emergency response: a one and half year observational study (preprint)

Background Primary healthcare workforce (PHCW) should be suffered from less burnout after the termination of the COVID-19 response. The current study compared the changes in the three dimensions of burnout in PHCW during and after the response. Methods  Two convenience-sampling, online, cross-sectional questionnaire studies were conducted in local PHCW. Studies were administered in April, 2022 and eight months after the termination. Burnout was measured by the Chinese version of 15-item Maslach Burnout Inventory-General Survey (MBI-GS), which assesses three dimensions: emotional exhaustion (EE), depersonalization (DP) and reduced personal accomplishment (reduced PA). The primary outcome was the prevalence of its three dimensions. Data on demographics, work environment, health conditions and outlets for stress reduction were collected. We compared burnout and associated factors between the study periods by using Student’s t-, chi-, or Mann‒Whitney tests. The associations between factors and burnout was identified by a logistic regression model. Results  In total, 162 and 200 participants completed the questionnairesduring and after the response. No significant differences in demographics, including age, gender, education attainment, work experience or seniority level were observed. The prevalence of burnout-free status was similar (9.9% vs. 12.5%, P=0.434) between thetwo periods. Severe burnout decreasedfrom 45.7% to zero%, and moderate burnout nearly doubled after the response. The prevalence of EE decreased the most, by 55.0%, followed by that of DP, which decreased by38.4% (all P<0.001); however, there wasno difference in the prevalence of reduced PA (77.2% vs. 74.5%, P=0.557). Logistic regression showed thatpromotion and alcohol consumption decreased the risk of EE. Considering leaving the job increases the risk of DP. A lowerself-evaluated health score and more distress were associated with EE and DP. Exercise decreased the risk of reduced PA. Conclusions Inconsistent with hypothesis, we found that severe burnout decreased but moderate burnout increased in PHCWs after the response. EE and DP decreased more, but reduced PA had no change. Incentives, improved self-evaluated health conditions, alcohol consumption and exercise ameliorate burnout. Healthcare policy makers must consider multiple effective ways to mitigate burnout in the post-epidemic era.

Shared genetic architecture and causal relationship between the age at first sex and COVID-19: A large-scale cross-trait analysis (preprint)

COVID-19 is genetically associated with numerous immune disorders, and young age at first intercourse (AFS) may lead to early activation of innate immunity. However, the genetic overlap between COVID-19 and AFS remains undetermined. Here we perform a large-scale cross-trait analysis to investigate their shared genetic etiology and causal relationship. An overall negative genetic correlation between the AFS and three COVID-19 traits was observed. We further identified 186, 221, and 213 shared genetic loci for AFS-COVID-19 infection, hospitalization, and severity, respectively. Among these shared loci, those closest to the genes CADM2, and ARPC1B showed the strongest signals. Our post-GWAS functional analysis revealed that the shared mapped genes were mainly involved in neural genesis and development within several brain structures. Finally, bidirectional Mendelian randomization (MR) results showed that earlier sexual debut may increase the risk of SARS-CoV-2 infection, hospitalization, and severity.

T-cell Immunity Against COVID-19 and UK Variant in Infected and Vaccinated Individuals (preprint)

Understanding the composition of human immune responses to SARS-CoV-2 and vaccines is essential for predicting protection from infection and determining vaccine efficacy. Here, we explored T-cell immune responses to SARS-CoV-2 and the UK (B.1.1.7) variant of concern (VOC) in infected and vaccinated individuals. In infected patients, CD4+ T-cells demonstrated consistent, robust responses against Spike peptides, while CD8+ T-cells had heterogeneous responses to 5 SARS-CoV-2 proteins. We found 80% of infected and vaccinated individuals showed positive CD4+ T-cell immunity against SARS-CoV-2. Moreover, CD4+/CD8+ T-cell responses to SARS-CoV-2 and the United Kingdom (B.1.1.7) variant are robust and nearly identical in infected and vaccinated individuals. Thus, the UK variant did not interfere with T-cell recognition and elicited responses. These observations will be of critical importance in assessing human immune responses to emerging VOCs.

Clinical analysis of liver dysfunction in pregnant patients with mild SARS CoV-2 infection

Objective: The current study aimed to describe the clinical characteristics of mild SARS-CoV-2 infected pregnant women with abnormal liver function (ALF), explore the association between ALF with maternal and fetal outcomes. Method(s): This retrospective analysis included 87 pregnant patients with mild SARS-CoV-2 infection admitted and treated from December 1, 2022, to 31, 2022 in the department of Obestircs at Beijing Obstetrics and Gynecology Hospital. We evaluated patients for demographic and clinical features, laboratory parameters and pregnancy complications. Result(s): 27 Patients in this cohort had clinical presentations of ALF. Compared with the control group, the peripheral blood platelet (PLT), D-dimer quantitative determination (D-Dimer), lactate dehydrogenase (LDH), total protein (TP), albumin (ALB), indirect bilirubin (DBIL), gamma- glutamyltranspeptidase (GGT) and total bile acid (TBA) showed significantly differences (p<0.05). 12 cases (44.44%) complicated with pregnancy induced hypertension (PIH), 14 cases (51.85%) complicated with intrahepatic cholestasis of pregnancy (ICP), 2 cases (7.4%) complicated with acute fatty liver during pregnancy (AFLP) and 5 cases (14.81%) complicated with postpartum hemorrhage in patients with abnormal LFT were significantly higher than those in the control group (p<0.05). Compared with the control group, the incidence of premature delivery (22.22%) and fetal distress (37.04%) in the experiment group were significantly higher (p<0.05), and the incidence of neonatal asphyxia was not significantly different (p>0.05). Conclusion(s): Pregnant women are generally susceptible to mild SARS-CoV-2 and may induce ALF. ALF is associated with increased risk of mother and infant. The maternal and infant outcomes of those who terminated pregnancy in time are acceptable. Therefore, pregnant women with COVID-19 who received antiviral treatment should be closely monitored for evaluating liver function and relevant indicators. The long-term outcomes in the future are worth to further study.Copyright © 2023

Managing the menopause during the pandemic

The structure of the presentation will be 1) Pandemic-Epidemiology 2) General Pandemic-Management 3) HRT and COVID 4) Different spectrum of menopausal symptoms (Europe/Asia) 5) Different risks lead to different HRT. 1) Pandemic-Epidemiology: SARS-COVID-19 has got to be a new disease, China was the first to suffer from the pandemic starting in December 2019 with spread all over the world. Diagnosis, treatment and protective measures have started in Europe in March 2020;up from autumn 2022 in Europe the pandemic changed to endemic, but protective measures still should be continued in risk patients like in hospitals and nursing homes. Rehabilitation will for long-time be an issue like treatment of "Post-" and "Long-COVID". China pursued a zero-COVID-policy until Dec 2022. The sudden stop of almost all measures led to a sharp increase in infections, which shows that the disease will remain a global risk. 2) General Pandemic-Management: Protective measures like vaccination, surgical masks, screening/testing, isolation management, travel/residence history in high-risk regions, education of patients and families had to be the first priority, ahead of other issues such as the management of menopause. 3) HRT and COVID: Already the first prelimary data assessed in Wuhan/China have shown that women with low estradiol-levels had more severe infections with COVID. An analysis of health records of 68,466 COVID-positive patients from 17 countries showed that the fatality risk for women > 50 years receiving HRT was reduced by more than 50% compared to those women not taking HRT (Seeland, 2020). Likewise from a case-control study analyzing the self-reported data of 1.6 million UK menopausal women through the COVID-Symptoms Study Smartphone application (control populations adjusted for age, body mass index, and smoking status) was concluded, that HRT not only can be used, but even can protect from COVID-infections and/or their sequelae (Costeira, 2021). 4) The different spectrum of menopausal symptoms (independent of COVID-infections) comparing data in Europe (showing more vasomotor symptoms) and China (more somatic symptoms) will be presented, including own data. 5) Different risks during HRT consequently lead to different use of HRT, especially more transdermal estrogen combined with progesterone in Europe due to much higher VTE-risk, but more management of the high bleeding-problems in China using individualized (mostly oral) estrogen/progestogen combinations. Copyright © 2023

Erratum: Inhaled ACE2-engineered microfluidic microsphere for intratracheal neutralization of COVID-19 and calming of the cytokine storm.

[This corrects the article DOI: 10.1016/j.matt.2021.09.022.].

Emerging Digital Practices Supporting Student-Centered Learning Environments in Higher Education: A Review of Literature and Lessons Learned from the Covid-19 Pandemic.

The aim of this paper is two-fold: firstly, to provide an overview of emerging digital practices that support collaborative learning, competency development, and digital literacy for student-centered learning environments in higher education during the rapid digital transition caused by pandemic-related lockdowns across the world, and secondly, to analyze and discuss how systematic reviews of generalized themes and trends can be combined with contextualized experiences and the lessons learned from the Covid-19 crisis to inform the digital transformation of higher education, with a particular focus on bridging the gap between campus-based teaching and online learning and on the identification of the digital competencies that teachers and students must acquire during the continuing shift into a 'new normal' for post-pandemic educational practices. This study was motivated by questions and findings emerging from an early reactive case study conducted by three of this paper's co-authors (Lyngdorf et al., 2021a). By reviewing the full texts of 18 articles, this study provides a systematic literature review which maps the general landscape of the online, hybrid, and blended digital practices applied in existing student-centered learning environments in higher education since the onset of the pandemic. Furthermore, this mapping is used to revisit data and findings from the earlier reactive study of emerging digital practices in a specific problem- and project-based learning (PBL) environment. This study's findings highlight critical factors and barriers related to emerging practices which support students' interactions with teachers, content, and each other, as well as the emerging competencies that these practices will require. The paper concludes with a discussion of the main findings and their implications for further research and practice.

A Review of the COVID-19 Mental Health Impact in Post-Conflict Settings: Bridging the Mental Health Gap with Case Exemplars from an Implementation Science Lens.

The COVID-19 pandemic has further aggravated the burden of mental health and presents an opportunity for public health research to focus on evidence-based interventions appropriate for populations residing in resource-constrained, post-conflict settings. Post-conflict settings have a higher service gap in mental health and fewer protective factors, such as economic and domestic security. Post-conflict settings are defined as locations where open warfare has ended but resulting challenges have remained for years. A strong emphasis on the engagement of diverse stakeholders is needed to arrive at sustainable and scalable solutions to mental health service delivery. This review discusses mental health service delivery gaps in post-conflict settings, highlights the urgency of the matter in the context of the COVID-19 pandemic, and provides recommendations for service gaps from evidence-based case study exemplars with an implementation science lens using the Consolidated Framework for Implementation Research (CFIR) as guide to improving adaptation and uptake.

Diagnosis and Treatment Strategy of Nasogenic Olfactory Dysfunction.

Since the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a symptom of the onset of SARS-CoV-2, olfactory dysfunction (OD), has attracted tremendous attention. OD is not only a negative factor for quality of life but also an independent hazard and early biomarker for various diseases, such as Parkinson's and Huntington's diseases. Therefore, early identification and treatment of OD in patients are critical. Many etiological factors are responsible for OD based on current opinions. Sniffin'Sticks are recommended to identify the initial position (central or peripheral) for OD when treating patients clinically. It is worth emphasizing that the olfactory region in nasal cavity is recognized as the primary and critical olfactory receptor. Many nasal diseases, such as those with traumatic, obstructive and inflammatory causes, can lead to OD. The key question is no refined diagnosis or treatment strategy for nasogenic OD currently. This study summarizes the differences in medical history, symptoms, auxiliary examination, treatment and prognosis of different types of nasogenic OD by analyzing the current studies. We propose using olfactory training after 4-6 weeks of initial treatment for nasogenic OD patients with no significant improvement in olfaction. We hope that our research can provide valuable clinical guidance by systematically summarizing the clinical characteristics of nasogenic OD.

Impact of the COVID-19 pandemic on cancer diagnoses, stage and survival in Alberta.

BACKGROUND: The COVID-19 pandemic is suspected to have affected cancer care and outcomes among patients in Canada. In this study, we evaluated the impact of the state of emergency period during the COVID-19 pandemic (Mar. 17 to June 15, 2020) on cancer diagnoses, stage at diagnosis and 1-year survival in Alberta. METHODS: We included new diagnoses of the 10 most prevalent cancer types from Jan. 1, 2018, to Dec. 31, 2020. We followed patients up to Dec. 31, 2021. We used interrupted time series analysis to examine the impact of the first COVID-19-related state of emergency in Alberta on the number of cancer diagnoses. We used multivariable Cox regression to compare 1-year survival of the patients who received a diagnosis during 2020 after the state of emergency with those who received a diagnosis during 2018 and 2019. We also performed stage-specific analyses. RESULTS: We observed significant reductions in diagnoses of breast cancer (incidence rate ratio [IRR] 0.67, 95% confidence interval [CI] 0.59-0.76), prostate cancer (IRR 0.64, 95% CI 0.56-0.73) and colorectal cancer (IRR 0.64, 95% CI 0.56- 0.74) and melanoma (IRR 0.57, 95% CI 0.47-0.69) during the state of emergency period compared with the period before it. These decreases largely occurred among early-stage rather than late-stage diagnoses. Patients who received a diagnosis of colorectal cancer, non-Hodgkin lymphoma and uterine cancer in 2020 had lower 1-year survival than those diagnosed in 2018; no other cancer sites had lower survival. INTERPRETATION: The results from our analyses suggest that health care disruptions during the COVID-19 pandemic in Alberta considerably affected cancer outcomes. Given that the largest impact was observed among early-stage cancers and those with organized screening programs, additional system capacity may be needed to mitigate future impact.

Design and Identification of Inhibitors for the Spike-ACE2 Target of SARS-CoV-2.

When an epidemic started in the Chinese city of Wuhan in December 2019, coronavirus was identified as the cause. Infection by the virus occurs through the interaction of viral S protein with the hosts' angiotensin-converting enzyme 2. By leveraging resources such as the DrugBank database and bioinformatics techniques, ligands with potential activity against the SARS-CoV-2 spike protein were designed and identified in this investigation. The FTMap server and the Molegro software were used to determine the active site of the Spike-ACE2 protein's crystal structure. Virtual screening was performed using a pharmacophore model obtained from antiparasitic drugs, obtaining 2000 molecules from molport®. The ADME/Tox profiles were used to identify the most promising compounds with desirable drug characteristics. The binding affinity investigation was then conducted with selected candidates. A molecular docking study showed five structures with better binding affinity than hydroxychloroquine. Ligand_003 showed a binding affinity of -8.645 kcal·mol-1, which was considered an optimal value for the study. The values presented by ligand_033, ligand_013, ligand_044, and ligand_080 meet the profile of novel drugs. To choose compounds with favorable potential for synthesis, synthetic accessibility studies and similarity analyses were carried out. Molecular dynamics and theoretical IC50 values (ranging from 0.459 to 2.371 µM) demonstrate that these candidates are promising for further tests. Chemical descriptors showed that the candidates had strong molecule stability. Theoretical analyses here show that these molecules have potential as SARS-CoV-2 antivirals and therefore warrant further investigation.

Association between the level of concern for COVID-19 and information sources among college students (preprint)

Objective We administered an online survey to 185 college students to assess their level of concern, information sources, and mitigation strategies during the COVID-19 pandemic in 2021. Responses from only students enrolled in college during 2021 were analyzed. We sought to examine their level of concern as defined as utilization of protective measures and/or personal protective equipment and/or social distancing and/or following other public health recommendations from public health sources.  Results College students that participated in our survey used various sources to obtain information about COVID-19 that included social media and other sources (58.92%), followed by mainstream media (27.57%) and email from their university/college (13.51%). Students who learned about the pandemic from social media (65.94%) were concerned; however, only 23.19% and 10.87% of the participants that sourced information from mainstream media and their schools’ email, respectively, were concerned. Furthermore, students who received information from social media and other sources were three times more likely to be concerned about COVID-19 than students who received information from the university via email.

A scoping review of non-professional medication practices and medication safety outcomes during public health emergencies.

OBJECTIVES: Public health emergencies (PHE) can disrupt personal medication practices and increase the risk of medication-related harm and other negative medication-related outcomes. Our aim was to examine the extent and nature of published research on this topic to guide future research and practice. STUDY DESIGN: Scoping review. METHODS: Standard electronic databases were searched. PRISMA-ScR guidelines were followed. Extracted data were organised in response to review questions and narrative accounts developed. RESULTS: A total of 129 studies were included, conducted across 32 countries, mostly in the USA (n = 42). Sixty-eight (53%) reported on infectious events, 49 (39%) climatological or ecological events and the remainder a mixture of terrorism, war or other disasters. The studies described several medication safety outcomes (medication-related harm, adherence, supply) and adaptive medication practices (self-altering prescribed medications, sharing medications and changing healthcare providers). Challenges to maintaining routine medication practices during a PHE included transport, finance, quarantine and knowledge-related issues. Twenty-eight studies (22%) examined health inequalities pertaining to adverse medication-related outcomes, with findings suggesting that gender, age, ethnicity, educational and socio-economic status may be related to inequalities. Research gaps identified included carers', children's and minority communities' experiences and intervention studies. CONCLUSIONS: There is considerable evidence of disruptions to routine personal medication practices during PHEs and of medication-related harm and other negative outcomes. Maintaining medication supply for the management of chronic conditions is a universal problem across all emergency types. Research is needed to address these disruptions, particularly amongst people who experience health inequalities who may need additional support.

Investigating the cumulative lag effects of environmental exposure under urban differences on COVID-19.

Although all walks of life are paying less attention to COVID-19, the spread of COVID-19 has never stopped. As an infectious disease, its transmission speed is closely related to the atmosphere environment, particularly the temperature (T) and PM2.5 concentrations. However, How T and PM2.5 concentrations are related to the spread of SARS-CoV-2 and how much their cumulative lag effect differ across cities is unclear. To identify the characteristics of cumulative lag effects of environmental exposure under city differences, this study used a generalized additive model to investigate the associations between T/PM2.5 concentrations and the daily number of new confirmed COVID-19 cases (NNCC) during the outbreak period in the second half of 2021 in Shaoxing, Shijiazhuang, and Dalian. The results showed that except for PM2.5 concentrations in Shaoxing, the NNCC in the three cities generally increased with the unit increase of T and PM2.5 concentrations. In addition, the cumulative lag effects of T/PM2.5 concentrations on NNCC in the three cities reached a peak at lag 26/25, lag 10/26, and lag 18/13 days, respectively, indicating that the response of NNCC to T and PM2.5 concentrations varies among different regions. Therefore, combining local meteorological and air quality conditions to adopt responsive measures is an important way to prevent and control the spread of SARS-CoV-2.

Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.

Background: The safety of COVID-19 vaccines has been clarified in clinical trials; however, some immunocompromised patients, such as myasthenia gravis (MG) patients, are still hesitant to receive vaccines. Whether COVID-19 vaccination increases the risk of disease worsening in these patients remains unknown. This study aims to evaluate the risk of disease exacerbation in COVID-19-vaccinated MG patients. Methods: The data in this study were collected from the MG database at Tangdu Hospital, the Fourth Military Medical University, and the Tertiary Referral Diagnostic Center at Huashan Hospital, Fudan University, from 1 April 2022 to 31 October 2022. A self-controlled case series method was applied, and the incidence rate ratios were calculated in the prespecified risk period using conditional Poisson regression. Results: Inactivated COVID-19 vaccines did not increase the risk of disease exacerbation in MG patients with stable disease status. A few patients experienced transient disease worsening, but the symptoms were mild. It is noted that more attention should be paid to thymoma-related MG, especially within 1 week after COVID-19 vaccination. Conclusion: COVID-19 vaccination has no long-term impact on MG relapse.

Clinical observation of Suhexiang Pills in treatment of patients infected with SARS-CoV-2

Objective To explore the clinical effect and safety of Suhexiang Pills () in the treatment of patients infected with SARS-CoV-2. Methods A total of 192 patients infected with SARS-CoV-2 admitted to 17 hospitals including Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University from December 2022 to January 2023 were randomly divided into control group and treatment group, with 89 patients in the treatment group and 103 in the control group. The patients in control group received basic treatment according to the Diagnosis and Treatment Protocol for COVID-19 (Trial Version 10). The patients in treatment group were oral administered with Suhexiang Pills on the basis of the control group, one pill each time, twice day. The patients in two groups were treated for 5 d. The clinical efficacy of the two groups after treatment was compared. The differences in scores of headache, chest pain, limb pain and inflammatory indexes before and after treatment were compared. Results After treatment, the total clinical effective rate of the treatment group was 95.51%, which was significantly higher than that of the control group (81.55%, P < 0.05). After treatment, headache, chest pain and limb pain scores were significantly decreased in both groups (P < 0.05), the headache score of the treatment group was significantly lower than that of the control group from the first day of treatment (P < 0.05), the chest pain score of the treatment group was significantly lower than that of the control group on the fifth day of treatment (P < 0.05), the limb pain score of the treatment group was significantly lower than that of the control group from the third day of treatment (P < 0.05). After treatment, the levels of C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6) in the two groups were decreased significantly (P < 0.05) and the levels of CRP and IL-6 in the treatment group were significantly lower than those of the control group (P < 0.05). There was no significant difference in the incidence of adverse events between the two groups. Conclusion Suhexiang Pills have a certain effect on headache, chest pain and limb pain, inhibiting the inflammatory response in patients infected with SARS-CoV-2, with good safety.Copyright © 2023 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.