Protective effect of ursodeoxycholic acid on COVID-19 in patients with chronic liver disease.

Objective: Ursodeoxycholic acid (UDCA) may reduce susceptibility to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection by downregulating angiotensin-converting enzyme 2 (ACE2), based on recent experimental investigation. This study aimed to determine the potential protective effect of UDCA against SARS-CoV-2 infection in patients with chronic liver disease. Methods: Patients with chronic liver disease receiving UDCA (taking UDCA ≥1 month) at Beijing Ditan Hospital between January 2022 and December 2022 were consecutively enrolled. These patients were matched in a 1:1 ratio to those with liver disease not receiving UDCA during the same period by using a propensity score matching analysis with nearest neighbor matching algorithm. We conducted a phone survey of coronavirus disease 2019 (COVID-19) infection during the early phase of the pandemic liberation (from 15 December 2022 to 15 January 2023). The risk of COVID-19 was compared in two matched cohorts of 225 UDCA users and 225 non-UDCA users based on patient self-report. Results: In the adjusted analysis, the control group was superior to the UDCA group in COVID-19 vaccination rates and liver function indicators, including γ-glutamyl transpeptidase and alkaline phosphatase (p < 0.05). UDCA was associated with a lower incidence of SARS-CoV-2 infection (UDCA 85.3% vs. control 94.2%, p = 0.002), more mild cases (80.0% vs. 72.0%, p = 0.047), and shorter median time from infection to recovery (5 vs. 7 days, p < 0.001). Logistic regression analysis showed that UDCA was a significant protective factor against COVID-19 infection (OR: 0.32, 95%CI: 0.16-0.64, p = 0.001). Furthermore, diabetes mellitus (OR: 2.48, 95%CI: 1.11-5.54, p = 0.027) and moderate/severe infection (OR: 8.94, 95%CI: 1.07-74.61, p = 0.043) were more likely to prolong the time from infection to recovery. Conclusion: UDCA therapy may be beneficial in reducing COVID-19 infection risk, alleviating symptoms, and shortening the recovery time in patients with chronic liver disease. However, it should be emphasized that the conclusions were based on patient self-report rather than classical COVID-19 detection by experimental investigations. Further large clinical and experimental studies are needed to validate these findings.

Effects of COVID-19 pandemic on mental health among frontline healthcare workers: A systematic review and meta-analysis.

Background: As some countries announced to remove Coronavirus Disease 2019 (COVID-19) border, it indicates that the COVID-19 may have entered its terminal stage. In this COVID-19 pandemic, the mental health of frontline healthcare workers (HCWs) experienced unprecedented challenges. However, the impact of the COVID-19 pandemic on mental health among frontline HCWs lacks a high-quality and long-term systematic review and meta-analysis. Methods: We conducted a systematic review and meta-analysis according to PRISMA guidelines. The system searches EMBASE, MEDLINE, PsycINFO, Cochrane Library, ScienceNet, and ERIC. Analyze the mental health problems of frontline HCWs in different regions and periods, including insomnia, stress, anxiety and depression. This study was registered in PROSPERO under the number CRD42021253821. Results: A total of 19 studies on the effects of COVID-19 pandemic on mental health among frontline HCWs were included in this study. The overall prevalence of insomnia was 42.9% (95% CI, 33.9-51.9%, I 2 = 99.0%) extracted from data from 14 cross-sectional studies (n = 10 127), 1 cohort study (n = 4,804), and 1 randomized controlled trial (RCT; n = 482) in 10 countries. The overall prevalence of stress was 53.0% (95% CI, 41.1-64.9%, I 2 = 78.3%) extracted from data from nine cross-sectional studies (n = 5,494) and 1 RCT study (n = 482) from eight countries. The overall prevalence of anxiety and depression was 43.0% (95% CI, 33.8-52.3%, I 2 = 99.0%) and 44.6% (95% CI, 36.1-53.1%, I 2 = 99.0%) extracted from data from 17 cross-sectional studies (n = 11,727), one cohort study (n = 4,804), and one RCT study (n = 482) from 12 countries. The prevalence of stress and depression was higher in 2020, while the prevalence of insomnia and anxiety was higher in 2021. The prevalence of mental health problems among physicians was higher than that of other frontline HCWs. The prevalence of mental health problems among frontline HCWs is higher in South America and lower in North America. Conclusions: This systematic review and meta-analysis showed that the COVID-19 pandemic have significant effects on mental health among frontline HCWs. The overall prevalence of insomnia, stress, anxiety and depression among frontline HCWs is high. Therefore, the health policy-makers should pay attention to and respond to the mental health problems of frontline HCWs in the context of public health emergencies. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/.

Relationship between nurses' psychological capital and satisfaction of elderly cancer patients during the COVID-19 pandemic.

Introduction: As a special vulnerable group, the physical and mental health of elderly cancer patients has attracted much attention. However, few studies have focused on the impact of nurses' mental state on the mental health of elderly cancer patients during the COVID-19 pandemic. In response to this literature gap, this study aims to explore the impact of nurses' psychological capital on the satisfaction of elderly cancer patients. The job demands-resources model (JD-R) is used to further investigate how work engagement and job resources of nurses affect this relationship. Methods: The questionnaire survey was used to collect data, participants included 230 elderly cancer patients and their nurses from a tertiary first-class cancer hospital in China. Partial least squares structural equation modeling (PLS-SEM) was conducted with SmartPLS 3.3.9. Results: Nurses' psychological capital has a significant positive impact on the satisfaction of elderly cancer patients during the COVID-19 pandemic. Nurses' work engagement is an important mechanism for their psychological capital to affect the satisfaction of elderly cancer patients. In addition, nurses' job resources positively moderate the relationship between their psychological capital and work engagement. The positive relationship between psychological capital and work engagement of nurses is stronger when they have abundant job resources. Discussion: These findings suggest that healthcare organizations should take the psychological capital of medical staff as an important means to improve their competitive advantage. It can improve the quality of medical services to obtain good performance by effectively developing and managing the psychological capital of medical staff. In addition, healthcare organizations should recognize the importance of providing adequate job resources for medical staff.

The relationship between the sources of confidence in overcoming COVID-19 and the improvement of medical students' professional identity: mediation by medical students' attention to COVID-19.

BACKGROUND: The prevalence of COVID-19 highlights the shortage of human medical resources, and improving medical students' professional identity is crucial to improving this situation. The sources of confidence in overcoming COVID-19 and medical students' attention to COVID-19 were significant factors affecting their professional identity. However, no study has investigated the mediating role of medical students' attention to COVID-19 in their relationship. This study investigates the relationship between these three factors in three medical university students in Hunan Province. METHODS: A cross-sectional survey study that used convenience sampling method was conducted on 2775 medical students from three universities in the Hunan Province of China from March 15 to April 19, 2020. An intermediary model was established to evaluate the role of medical students' attention to COVID-19 in the sources of confidence in overcoming COVID-19 and the improvement of medical students' professional identity. RESULTS: The sources of confidence in overcoming COVID-19, medical students' attention to national crisis events, and the improvement of medical students' professional identity was positively associated with each other (ß = 0.328 ~ 0.464, P < 0.001). The mediating effect accounted for 23.3% of the total effect and 30.4% of the direct effect. Medical students' attention to COVID-19 partially mediates the relationship between the sources of confidence to overcome COVID-19 and the improvement of medical students' professional identity. CONCLUSIONS: This study found that the sources of confidence in overcoming COVID-19 and medical students' attention to national crisis events have a significant predictive effect on the improvement of medical students' professional identity. Medical students' attention to COVID-19 mediated the relationship between the sources of confidence to overcome COVID-19 and the improvement of medical students' professional identity. The findings have emphasized the theoretical and practical significance of professional identity education for medical students.

Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2.

There is an urgent need for animal models to study SARS-CoV-2 pathogenicity. Here, we generate and characterize a novel mouse-adapted SARS-CoV-2 strain, MASCp36, that causes severe respiratory symptoms, and mortality. Our model exhibits age- and gender-related mortality akin to severe COVID-19. Deep sequencing identified three amino acid substitutions, N501Y, Q493H, and K417N, at the receptor binding domain (RBD) of MASCp36, during in vivo passaging. All three RBD mutations significantly enhance binding affinity to its endogenous receptor, ACE2. Cryo-electron microscopy analysis of human ACE2 (hACE2), or mouse ACE2 (mACE2), in complex with the RBD of MASCp36, at 3.1 to 3.7 Å resolution, reveals the molecular basis for the receptor-binding switch. N501Y and Q493H enhance the binding affinity to hACE2, whereas triple mutations at N501Y/Q493H/K417N decrease affinity and reduce infectivity of MASCp36. Our study provides a platform for studying SARS-CoV-2 pathogenesis, and unveils the molecular mechanism for its rapid adaptation and evolution.

Characteristics of COVID-19 patients with preexisting CKD history.

PURPOSE: This paper was intended to describe the characteristics of coronavirus disease 2019 (COVID-19) patients with known chronic kidney disease (CKD) history. METHODS: Clinical information of 20 COVID-19 pneumonia patients with CKD history diagnosed between January 20th and March 1st, 2020 were collected in Tongji Hospital, Wuhan. We listed the clinical baseline data, laboratory findings, chest computed tomography (CT) changes and processed a short period of follow-up of these 20 patients. RESULTS: Based on the estimated glomerular filtration rate (eGFR) on admission, 6 patients were classified as stage 2 of CKD, 5 were as 3a, 2 were as 3b, 3 were as 4 and 4 were as 5, respectively. COVID-19 patients with CKD history were elder and hypertension was the most common comorbidity. Cough and fever accounted for more than 80% of the infectious cases. Lymphopenia, increased D-dimer and elevated infectious indications such as hypersensitive C response protein (hsCRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were also common among these patients. Ground-glass opacity (GGO) and consolidation were the major manifestations in CT scans. 4 patients died and 7 patients underwent acute kidney injury (AKI) during observation. Among 16 discharged patients, 12 were with stable renal function and 4 had deteriorating renal function compared with that of admission. CONCLUSION: Compared to general population infected with SARS-CoV-2, COVID-19 patients with CKD history had a preference to develop to severity with higher fatality rate.

Morphogenesis and cytopathic effect of SARS-CoV-2 infection in human airway epithelial cells.

SARS-CoV-2, a ß-coronavirus, has rapidly spread across the world, highlighting its high transmissibility, but the underlying morphogenesis and pathogenesis remain poorly understood. Here, we characterize the replication dynamics, cell tropism and morphogenesis of SARS-CoV-2 in organotypic human airway epithelial (HAE) cultures. SARS-CoV-2 replicates efficiently and infects both ciliated and secretory cells in HAE cultures. In comparison, HCoV-NL63 replicates to lower titers and is only detected in ciliated cells. SARS-CoV-2 shows a similar morphogenetic process as other coronaviruses but causes plaque-like cytopathic effects in HAE cultures. Cell fusion, apoptosis, destruction of epithelium integrity, cilium shrinking and beaded changes are observed in the plaque regions. Taken together, our results provide important insights into SARS-CoV-2 cell tropism, replication and morphogenesis.

[Intervention mechanism of Qingwen Baidu Yin on cytokine storm based on network pharmacology].

The aim of this paper was to explore the intervention mechanism of Qingwen Baidu Yin in cytokine storm based on network pharmacology. TCMSP and TCMIP V2.0 server were used to predict all chemical components and action targets of Qingwen Baidu Yin. Diseases that could be treated by Qingwen Baidu Yin were predicted through Enrichr database. A compound target interaction(PPI) network diagram was constructed using STRING 11.0. OmicShare was used to analyzed the gene ontology(GO) enrichment and enrichment of the Kyoto encyclopedia of genes and genomes(KEGG) pathway of core targets. Component-target-path network diagram was constructed with Cytoscape 3.6.0 software. After analysis of the database, 267 compounds were screened for Qingwen Baidu Yin, involving 1 450 targets, and a protein interaction network was constructed. Total 219 core target proteins were predicted, such as NFKB1, STAT1, RAF1, IL2, JAK1, IL6, TNF, BCL2 and other important targets, and 221 core target pathways were enriched, including cancer pathway, Kaposi's sarcoma-associated herpes virus infection, chemokine signal pathway, PI3 K-AKT signal pathway, EB virus infection, virus carcinogenesis and T cell receptor signaling pathways, a collection of which were highly related to cytokine storms. GO annotation analysis suggested that Qingwen Baidu Yin Decoction may exert therapeutic effects by regulating protein phosphorylation, cell response to cytokine stimulation, cell proliferation, inflammatory response, transmembrane receptor protein tyrosine kinase signaling pathway, and cytokine-mediated signaling pathways. This study revealed potential active components of Qingwen Baidu Yin in defending against cytokine storm and its possible mechanism of action, and provided theoretical basis and technical support for further clinical application of this prescription.

The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern1. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)2. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19.

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.

BACKGROUND: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. METHODS: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. FINDINGS: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. INTERPRETATION: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. FUNDING: National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.

A Novel Coronavirus from Patients with Pneumonia in China, 2019.

In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).