miRNAs derived from milk small extracellular vesicles inhibit porcine epidemic diarrhea virus infection.

Porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus in the family Coronaviridae, causes acute diarrhea and/or vomiting, dehydration, and high mortality in neonatal piglets. It has caused huge economic losses to animal husbandry worldwide. Current commercial PEDV vaccines do not provide enough protection against variant and evolved virus strains. No specific drugs are available to treat PEDV infection. The development of more effective therapeutic anti-PEDV agents is urgently needed. Our previous study suggested that porcine milk small extracellular vesicles (sEV) facilitate intestinal tract development and prevent lipopolysaccharide-induced intestinal injury. However, the effects of milk sEV during viral infection remain unclear. Our study found that porcine milk sEV, which was isolated and purified by differential ultracentrifugation, could inhibit PEDV replication in IPEC-J2 and Vero cells. Simultaneously, we constructed a PEDV infection model for piglet intestinal organoids and found that milk sEV also inhibited PEDV infection. Subsequently, in vivo experiments showed that milk sEV pre-feeding exerted robust protection of piglets from PEDV-induced diarrhea and mortality. Strikingly, we found that the miRNAs extracted from milk sEV inhibited PEDV infection. miRNA-seq, bioinformatics analysis, and experimental verification demonstrated that miR-let-7e and miR-27b, which were identified in milk sEV targeted PEDV N and host HMGB1, suppressed viral replication. Taken together, we revealed the biological function of milk sEV in resisting PEDV infection and proved its cargo miRNAs, miR-let-7e and miR-27b, possess antiviral functions. This study is the first description of the novel function of porcine milk sEV in regulating PEDV infection. It provides a better understanding of milk sEV resistance to coronavirus infection, warranting further studies to develop sEV as an attractive antiviral.

Engineering probiotic-derived outer membrane vesicles as functional vaccine carriers to enhance immunity against SARS-CoV-2.

Because of the continued emergence of SARS-CoV-2 variants, there has been considerable interest in how to display multivalent antigens efficiently. Bacterial outer membrane vesicles (OMVs) can serve as an attractive vaccine delivery system because of their self-adjuvant properties and the ability to be decorated with antigens. Here we set up a bivalent antigen display platform based on engineered OMVs using mCherry and GFP and demonstrated that two different antigens of SARS-CoV-2 could be presented simultaneously in the lumen and on the surface of OMVs. Comparing immunogenicity, ClyA-NG06 fusion and the receptor-binding domain (RBD) of the spike protein in the OMV lumen elicited a stronger humoral response in mice than OMVs presenting either the ClyA-NG06 fusion or RBD alone. Taken together, we provided an efficient approach to display SARS-CoV-2 antigens in the lumen and on the surface of the same OMV and highlighted the potential of OMVs as general multi-antigen carriers.

S100A4 exerts robust mucosal adjuvant activity for co-administered antigens in mice.

The lack of clinically applicable mucosal adjuvants is a major hurdle in designing effective mucosal vaccines. We hereby report that the calcium-binding protein S100A4, which regulates a wide range of biological functions, is a potent mucosal adjuvant in mice for co-administered antigens, including the SARS-CoV-2 spike protein, with comparable or even superior efficacy as cholera toxin but without causing any adverse reactions. Intranasal immunization with recombinant S100A4 elicited antigen-specific antibody and pulmonary cytotoxic T cell responses, and these responses were remarkably sustained for longer than 6 months. As a self-protein, S100A4 did not stimulate antibody responses against itself, a quality desired of adjuvants. S100A4 prolonged nasal residence of intranasally delivered antigens and promoted migration of antigen-presenting cells. S100A4-pulsed dendritic cells potently activated cognate T cells. Furthermore, S100A4 induced strong germinal center responses revealed by both microscopy and mass spectrometry, a novel label-free technique for measuring germinal center activity. Importantly, S100A4 did not induce olfactory bulb inflammation after nasal delivery, which is often a safety concern for nasal vaccination. In conclusion, S100A4 may be a promising adjuvant in formulating mucosal vaccines, including vaccines against pathogens that infect via the respiratory tract, such as SARS-CoV-2.

The roles of inactivated vaccines in older patients with infection of Delta variant in Nanjing, China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is spreading around the world. The COVID-19 vaccines may improve concerns about the pandemic. However, the roles of inactivated vaccines in older patients (aged ≥60 years) with infection of Delta variant were less studied. METHODS: We classified the older patients with infection of Delta variant into three groups based on the vaccination status: no vaccination (group A, n = 113), one dose of vaccination (group B, n = 46), and two doses of vaccination (group C, n = 22). Two inactivated COVID-19 vaccines (BBIBP-CorV or CoronaVac) were evaluated in this study. The demographic data, laboratory parameters, and clinical severity were recorded. RESULTS: A total of 181 older patients with infection of Delta variant were enrolled. 111 (61.3%) patients had one or more co-morbidities. The days of "turn negative" and hospital stay in Group C were lower than those in the other groups (P < 0.05). The incidences of multiple organ dysfunction syndrome (MODS), septic shock, acute respiratory distress syndrome (ARDS), acute kidney injury, and cardiac injury in Group A were higher than those in the other groups (P < 0.05). The MV-free days and ICU-free days during 28 days in Group A were also lower than those in the other groups (P < 0.05). In patients with co-morbidities, vaccinated cases had lower incidences of MODS (P = 0.015), septic shock (P = 0.015), and ARDS (P = 0.008). CONCLUSIONS: The inactivated COVID-19 vaccines were effective in improving the clinical severity of older patients with infection of Delta variant.

Clinical importance of second-opinion interpretations of abdominal imaging studies in a cancer hospital and its impact on patient management.

PURPOSE: The purpose of this retrospective study was to evaluate the quality of outside hospital imaging and associated reports submitted to us for reinterpretation related to clinical care at our tertiary cancer center. We compared the initial study interpretations to that of interpretations performed by subspecialty-trained abdominal radiologists at our center and whether this resulted in a change in inpatient treatment. MATERIALS AND METHODS: We performed an institutional review board-approved retrospective single-institution study of 915 consecutive outside computed tomography (CT) and magnetic resonance (MR) abdominal imaging studies that had been submitted to our institution between August 1, 2020 and November 30, 2020. The assessed parameters included the quality and accuracy of the report, the technical quality of the imaging compared to that at our institution, the appropriateness of the imaging for staging or restaging, usage of oral and IV contrast, and CT slice thickness. Clinical notes, pathologic findings, and subsequent imaging were used to establish an accurate diagnosis and determine the effect on clinical treatment. Discrepancies between the initial and secondary interpretations were identified independently by a panel of radiologists to assess changes in treatment. The impact of discrepancies on treatment was evaluated based on current treatment guidelines. RESULTS: Of 744 CT (81%) and 171 MR (19%) outside imaging studies, 65% had suboptimal quality compared to the images at our institution, and 31% were inappropriate for oncological care purposes. Only 21% of CT studies had optimal slice thickness of <3 mm. Of 375 (41%) outside reports, 131 (34%) had discrepancies between secondary and initial interpretations. Of the 88 confirmed discrepant studies, 42 patients (48%) had a change in treatment based on the secondary interpretation. CONCLUSIONS: Imaging studies from outside institutions have variable image quality and are often inadequate for oncologic imaging. The secondary interpretations by subspecialty-trained radiologists resulted in treatment change.

Experience of patients with COVID-19 in hospital isolation in Taiwan.

The COVID-19 pandemic has significantly impacted everyone's lives, challenging us in ways that can be frustrating, daunting, and intensely emotive. This qualitative study explored the isolation experiences of patients with COVID-19 in a hospital in northern Taiwan. We collected data from nine patients in June-July 2020, conducting semi-structured, virtual face-to-face, in-depth interviews to gather input on two topics: (1) the psychological effect of hospital isolation on patients, including the psychological burden, stress response, support, disease stigma, and fear of returning to society; and (2) the patients' cognition and behaviors, which included tracking epidemic information, monitoring disease progression, soliciting suggestions about hospital isolation, and gauging comprehension after recovery. The results confirmed that hospital isolation significantly impacts patients physically, psychologically, spiritually, and socially. Thus, the isolated patients faced the dual challenges of fighting, adapting to, and recovering from the disease itself and struggling in isolation to maintain positive beliefs, independently assess their condition, and gain strength from the knowledge of continuing social support.

What Causes the Most Stress in Breast Radiology Practice? A Survey of Members of the Society of Breast Imaging.

OBJECTIVE: The objective of this study is to determine the major stressors affecting practicing breast radiologists. METHODS: All members of the Society of Breast Imaging within the United States received an email invitation to complete an anonymous survey evaluating stressors that may contribute to physician burnout. Stressors evaluated included pace at work, work-life balance, care of dependents, job security, financial strain, decreasing reimbursement, new regulations, delivering bad news, fear of getting sued, and dealing with difficult patients, radiologists, and administrators. RESULTS: The overall response rate was 13.5% (312/2308). For those who opened the email, response rate was 24.6% (312/1269). The most prevalent stressors reported were working too fast (222/312, 71.2%), balancing demands of work with personal life (209/312, 70.0%), fear of getting sued (164/312, 52.6%), and dealing with difficult administrators (156/312, 50%). Prevalence of stress related to new regulation requirements, job security, financial strain, decreased reimbursement, dependent care, call, delivering bad news, and dealing with difficult patients, difficult referrers, and difficult radiologists were present in fewer than 50% of respondents. CONCLUSION: The most prevalent sources of stress in breast imaging radiologists relate to working too fast and balancing demands of work with time needed for personal life.

[Novel Coronavirus: Applying Transformational Leadership to the Combat of COVID-19 in Nursing Practice].

Cases in the current novel coronavirus (COVID-19) pandemic continue to increase, bringing tremendous psychological pressures to frontline caregivers and threating the ability of existing medical care systems in many countries to cope with related demands. In this situation, nursing leaders have a heightened responsibility to assist nursing staff to remain at their jobs and feel secure, to strengthen safety systems, to provide adequate equipment and personnel training, and to proactively lead nursing staff. In this article, leadership strategies implemented under the COVID-19 pandemic are presented from the perspective of transformational leadership in nursing practice. This article is divided into the following five themes: 1. Leadership makes the vision more vivid; 2. Demonstrating charismatic leadership; 3. Leaders who stimulate intellectual potential; 4. Paying attention to spiritual inspiration; 5. Providing individualized sincere care. Leaders should promote the professional role of nursing staff and provide a safe and secure practice environment.

Resilience, coping style, and COVID-19 stress: effects on the quality of life in frontline health care workers.

The aims of the study were to assess the contribution of resilience, coping style, and COVID-19 stress on the quality of life (QOL) in frontline health care workers (HCWs). The study was a cross-sectional surveyperformed among 309 HCWs in a tertiaryhospital during the outbreak of COVID-19 in China. Data were collected through an anonymous, self-rated questionnaire, including demographic data, a 10-item COVID-19 stress questionnaire, Generic QOL Inventory-74, Connor-Davidson Resilience Scale, and the Simplified Coping Style Questionnaire. Hierarchical regression was used to analyse the relationship between the study variables and the QOL. Among the 309 participants, resilience and active coping were positively correlated with the QOL (P<0.001), whereas, working in confirmed case wards, COVID-19 stress, and passive coping were negatively correlated with the QOL (P<0.001). Resilience and the active coping were negatively correlated with COVID-19 stress (P<0.001). Resilience, coping style,and COVID-19 stressaccounted for 32%, 13%, and 8% of the variance in predicting the Global QOL, respectively. In conclusion, working in confirmed COVID-19 case wards and COVID-19 stress impaired the QOL in HCWs. Psychological intervention to improve the resilience and coping style, and reduce COVID-19 stress are important in improving the QOL and mental health of HCWs.

Intestinal expression of ACE2 in mice with high-fat diet-induced obesity and neonates exposed to maternal high-fat diet.

OBJECTIVE: The 2019 novel coronavirus disease (COVID-19) is threatening global health and is especially pronounced in patients with chronic metabolic syndromes. Meanwhile, a significant proportion of patients present with digestive symptoms since angiotensin-converting enzyme 2 (ACE2), which is the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the intestine. The aim of this study was to evaluate the effects of a high-fat diet (HFD) and a maternal HFD on the intestinal ACE2 levels in adults and neonates. METHODS: We examined intestinal ACE2 protein levels in mice with diet-induced obesity (DIO) and neonatal mice exposed to a maternal HFD. We also investigated Ace2 mRNA expression in intestinal macrophages. RESULTS: Intestinal ACE2 protein levels were increased in DIO mice but decreased in offspring exposed to a maternal HFD compared with chow-fed controls. Ace2 mRNA expression in intestinal macrophages was detected and downregulated in DIO mice. Additionally, higher intestinal ACE2 protein levels were observed in neonates than in adult mice. CONCLUSIONS: The influence of an HFD on intestinal ACE2 protein levels is opposite in adults and neonates. Macrophages might also be involved in SARS-CoV-2 intestinal infection. These findings provide some clues for the outcomes of patients with COVID-19 with metabolic syndromes.

Lipid Profile Features and Their Associations With Disease Severity and Mortality in Patients With COVID-19.

Background: Emerging studies have described and analyzed epidemiological, clinical, laboratory, and radiological features of COVID-19 patients. Yet, scarce information is available regarding the association of lipid profile features and disease severity and mortality. Methods: We conducted a prospective observational cohort study to investigate lipid profile features in patients with COVID-19. From 9 February to 4 April 2020, a total of 99 patients (31 critically ill and 20 severely ill) with confirmed COVID-19 were included in the study. Dynamic alterations in lipid profiles were recorded and tracked. Outcomes were followed up until 4 April 2020. Results: We found that high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-1 (apoA-1) levels were significantly lower in the severe disease group, with mortality cases showing the lowest levels (p < 0.0001). Furthermore, HDL-C and apoA-1 levels were independently associated with disease severity (apoA-1: odds ratio (OR): 0.651, 95% confidence interval (CI): 0.456-0.929, p = 0.018; HDL-C: OR: 0.643, 95% CI: 0.456-0.906, p = 0.012). For predicting disease severity, the areas under the receiver operating characteristic curves (AUCs) of HDL-C and apoA-1 levels at admission were 0.78 (95% CI, 0.70-0.85) and 0.85 (95% CI, 0.76-0.91), respectively. For in-hospital deaths, HDL-C and apoA-1 levels demonstrated similar discrimination ability, with AUCs of 0.75 (95% CI, 0.61-0.88) and 0.74 (95% CI, 0.61-0.88), respectively. Moreover, patients with lower serum concentrations of apoA-1 (<0.95 g/L) or HDL-C (<0.84 mmol/l) had higher mortality rates during hospitalization (log-rank p < 0.001). Notably, levels of apoA-1 and HDL-C were inversely proportional to disease severity. The survivors of severe cases showed significant recovery of apoA-1 levels at the end of hospitalization (vs. midterm apoA-1 levels, p = 0.02), whereas the mortality cases demonstrated continuously lower apoA-1 levels throughout hospitalization. Correlation analysis revealed that apoA-1 and HDL-C levels were negatively correlated with both admission levels and highest concentrations of C-reactive protein and interleukin-6. Conclusions: Severely ill COVID-19 patients featured low HDL-C and apoA-1 levels, which were strongly correlated with inflammatory states. Thus, low apoA-1 and HDL-C levels may be promising predictors for severe disease and in-hospital mortality in patients suffering from COVID-19.

Acute gastrointestinal injury in critically ill patients with COVID-19 in Wuhan, China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is spreading rapidly around the world. Most critically ill patients have organ injury, including acute respiratory distress syndrome, acute kidney injury, cardiac injury, or liver dysfunction. However, few studies on acute gastrointestinal injury (AGI) have been reported in critically ill patients with COVID-19. AIM: To investigate the prevalence and outcomes of AGI in critically ill patients with COVID-19. METHODS: In this retrospective study, demographic data, laboratory parameters, AGI grades, clinical severity and outcomes were collected. The primary endpoints were AGI incidence and 28-d mortality. RESULTS: From February 10 to March 10 2020, 83 critically ill patients out of 1314 patients with COVID-19 were enrolled. Seventy-two (86.7%) patients had AGI during hospital stay, of these patients, 30 had AGI grade I, 35 had AGI grade II, 5 had AGI grade III, and 2 had AGI grade IV. The incidence of AGI grade II and above was 50.6%. Forty (48.2%) patients died within 28 days of admission. Multiple organ dysfunction syndrome developed in 58 (69.9%) patients, and septic shock in 16 (19.3%) patients. Patients with worse AGI grades had worse clinical variables, a higher incidence of septic shock and 28-d mortality. Sequential organ failure assessment (SOFA) scores (95%CI: 1.374-2.860; P < 0.001), white blood cell (WBC) counts (95%CI: 1.037-1.379; P = 0.014), and duration of mechanical ventilation (MV) (95%CI: 1.020-1.340; P = 0.025) were risk factors for the development of AGI grade II and above. CONCLUSION: The incidence of AGI was 86.7%, and hospital mortality was 48.2% in critically ill patients with COVID-19. SOFA scores, WBC counts, and duration of MV were risk factors for the development of AGI grade II and above. Patients with worse AGI grades had a higher incidence of septic shock and 28-d mortality.

Anxiety and depression in frontline health care workers during the outbreak of Covid-19.

BACKGROUND: The pandemic of coronavirus disease (Covid-19) seriously impacts the health and well-being of all of us. AIMS: We aim to assess the psychological impact of Covid-19 on frontline health care workers (HCWs), including anxiety, depression and stress of threat of the disease. METHOD: The study was a cross-sectional survey among the frontline HCWs in a hospital at Jinan, China. Data were collected through an anonymous, self-rated questionnaire, including basic demographic data, a 10-item Covid-19 stress questionnaire, the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS). The risk and rate of anxiety, depression and stress of Covid-19 were estimated. RESULTS: Among the 309 participants, there were 88 (28.5%) with anxiety and 172 (56.0%) with depression. Multivariate logistic regression analyses showed that age ⩽ 30 years, age > 30 to 45 years, working in confirmed case isolation wards, and worrying about disinfection measures being not sufficient were independently associated with anxiety with an odds ratio (95% confidence interval, CI) of 4.4 (1.6-12.2), 3.1 (1.1-8.8), 2.3 (1.4-4.0) and 2.5 (1.5-4.3), respectively; age ⩽ 30 years, age > 30 to 45 years, nurse and worrying about disinfection measure being not sufficient were independently associated with depression with an odds ratio (95% CI) of 3.8 (1.8-7.8), 2.7 (1.3-5.7), 2.5 (1.1-5.6) and 2.1 (1.3-3.5), respectively. CONCLUSIONS: A high prevalence of anxiety and depression was found among frontline HCWs during the COVID-19 outbreak. More psychological care should be given to young staffs and nurses. Measures to prevent professional exposure is important for HCWs' physical and mental health.

Spatial Agglomeration of Manufacturing in the Wuhan Metropolitan Area: An Analysis of Sectoral Patterns and Determinants

The important role of the entity economy, especially manufacturing, has been further highlighted after the outbreak of COVID-19. This study fills a research gap on manufacturing in the Wuhan Metropolitan Area by analyzing the spatio-temporal evolution patterns and characteristics of manufacturing, exploring the major location factors causing spatial reconstruction and comparing the effect intensities of the different factors in the manufacturing sector. From 2003 to 2018, the process of industrial suburbanization in the Wuhan Metropolitan Area continued to strengthen and currently the overall spatial pattern of manufacturing in the Wuhan Metropolitan Area is characterized by spreading in metropolitan areas and aggregation in industrial parks. The results of a spatial metering model showed that the dominant factors affecting the layout of manufacturing included innovation and technical service platforms, industrial parks, the number of large enterprises, living convenience, and air quality. However, the effect intensity of the different location factors varied among industries. The findings may help the government to understand the characteristics of agglomeration and spreading in the manufacturing industry and, in accordance with the dominant factors affecting the location of this industry, rationally develop ideas for adjusting the industrial layout in the post-coronavirus age.

The Role of Imaging Techniques in Management of COVID-19 in China: From Diagnosis to Monitoring and Follow-Up.

In December 2019, an outbreak of coronavirus infection emerged in Wuhan, Hubei Province of China, which is now named Coronavirus Disease 2019 (COVID-19). The outbreak spread rapidly within mainland China and globally. This paper reviews the different imaging modalities used in the diagnosis and treatment process of COVID-19, such as chest radiography, computerized tomography (CT) scan, ultrasound examination, and positron emission tomography (PET/CT) scan. A chest radiograph is not recommended as a first-line imaging modality for COVID-19 infection due to its lack of sensitivity, especially in the early stages of infection. Chest CT imaging is reported to be a more reliable, rapid, and practical method for diagnosis of COVID-19, and it can assess the severity of the disease and follow up the disease time course. Ultrasound, on the other hand, is portable and involves no radiation, and thus can be used in critically ill patients to assess cardiorespiratory function, guide mechanical ventilation, and identify the presence of deep venous thrombosis and secondary pulmonary thromboembolism. Supplementary information can be provided by PET/CT. In the absence of vaccines and treatments for COVID-19, prompt diagnosis and appropriate treatment are essential. Therefore, it is important to exploit the advantages of different imaging modalities in the fight against COVID-19.

Development and Validation of a Nomogram for Assessing Survival in Patients With COVID-19 Pneumonia.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has spread worldwide and continues to threaten peoples' health as well as put pressure on the accessibility of medical systems. Early prediction of survival of hospitalized patients will help in the clinical management of COVID-19, but a prediction model that is reliable and valid is still lacking. METHODS: We retrospectively enrolled 628 confirmed cases of COVID-19 using positive RT-PCR tests for SARS-CoV-2 in Tongji Hospital, Wuhan, China. These patients were randomly grouped into a training (60%) and a validation (40%) cohort. In the training cohort, LASSO regression analysis and multivariate Cox regression analysis were utilized to identify prognostic factors for in-hospital survival of patients with COVID-19. A nomogram based on the 3 variables was built for clinical use. AUCs, concordance indexes (C-index), and calibration curves were used to evaluate the efficiency of the nomogram in both training and validation cohorts. RESULTS: Hypertension, higher neutrophil-to-lymphocyte ratio, and increased NT-proBNP values were found to be significantly associated with poorer prognosis in hospitalized patients with COVID-19. The 3 predictors were further used to build a prediction nomogram. The C-indexes of the nomogram in the training and validation cohorts were 0.901 and 0.892, respectively. The AUC in the training cohort was 0.922 for 14-day and 0.919 for 21-day probability of in-hospital survival, while in the validation cohort this was 0.922 and 0.881, respectively. Moreover, the calibration curve for 14- and 21-day survival also showed high coherence between the predicted and actual probability of survival. CONCLUSIONS: We built a predictive model and constructed a nomogram for predicting in-hospital survival of patients with COVID-19. This model has good performance and might be utilized clinically in management of COVID-19.

Serum calcium as a biomarker of clinical severity and prognosis in patients with coronavirus disease 2019.

The aim of this study was to investigate the correlations between serum calcium and clinical outcomes in patients with coronavirus disease 2019 (COVID-19). In this retrospective study, serum calcium levels, hormone levels and clinical laboratory parameters on admission were recorded. The clinical outcome variables were also recorded. From February 10 to February 28, 2020, 241 patients were enrolled. Of these patients, 180 (74.7%) had hypocalcemia on admission. The median serum calcium levels were 2.12 (IQR, 2.04-2.20) mmol/L, median parathyroid hormone (PTH) levels were 55.27 (IQR, 42.73-73.15) pg/mL, and median 25-hydroxy-vitamin D (VD) levels were 10.20 (IQR, 8.20-12.65) ng/mL. The serum calcium levels were significantly positively correlated with VD levels (P =0.004) but negatively correlated with PTH levels (P =0.048). Patients with lower serum calcium levels (especially ≤2.0 mmol/L) had worse clinical parameters, higher incidences of organ injury and septic shock, and higher 28-day mortality. The areas under the receiver operating characteristic curves of multiple organ dysfunction syndrome, septic shock, and 28-day mortality were 0.923 (P <0.001), 0.905 (P =0.001), and 0.929 (P <0.001), respectively. In conclusion, serum calcium was associated with the clinical severity and prognosis of patients with COVID-19. Hypocalcemia may be associated with imbalanced VD and PTH levels.