Repurposing niclosamide as a novel anti-SARS-Cov-2 drug by restricting entry protein CD147.

Background The burst of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the global COVID-19 pandemic. But until today only limited numbers of drugs are discovered to treat COVID-19 patients. Even worse, the rapid mutations of SARS-CoV-2 compromise the effectiveness of existing vaccines and neutralizing antibodies due to the increased viral transmissibility and immune escape. CD147-spike protein, one of the entries of SRAR-CoV-2 into host cells, has been reported as a promising therapeutic target for developing drugs against COVID-19. Methods CRISPR-Cas9 induced gene knockout, western blotting, tet-off protein overexpression, ribonucleoprotein IP and RNA-IP were used to confirm the regulation of HuR on mRNA of CD147. Regulation of niclosamide on HuR nucleo-translocation was assessed by immunofluorescence staining of cell lines, IHC staining of tissue of mouse model and western blotting. Finally, the suppression of niclosamide on SARS-CoV-2 infection induced CD147 was evaluated by ACE2-expressing A549 cells and western blotting. Results We first discovered a novel regulation mechanism of CD147 via the RNA-binding protein HuR. We found that HuR regulates CD147 post-transcription by directly bound to its 3'-UTR. The loss of HuR reduced CD147 in multiple cell lines. Niclosamide inhibited CD147 function by blocking HuR cytoplasmic translocation and diminishing CD147 glycosylation. SARS-CoV-2 infection induced CD147 in ACE2-expressing A549 cells, which could be neutralized by niclosamide in a dose-dependent manner. Conclusion Together, our study reveals a novel regulation mechanism of CD147 and niclosamide can be repurposed as an effective COVID-19 drug by targeting the virus entry, CD147-spike protein.

Effects of an online training program on cardiovascular health behavior modification on nursing students' health education competency

Objectives The COVID-19 pandemic has forced many healthcare organizations to stop the placement of undergraduate nursing students. As a result, undergraduate nursing students need the necessary training and practice to increase their competency. Therefore, effective strategies are needed to improve the effectiveness of online internships. This study aims to evaluate the impact of online cardiovascular health behavior modification training on nursing undergraduate students' health education competency and clinical decision-making perceptions using the Conceive-Design-Implement-Operate (CDIO) model. Methods This study utilized quasi-experimental research with a non-equivalent control group design. Nursing students undergoing internships at Zhongshan Hospital, Fudan University, Shanghai, China, from June 2020 to December 2021 were enrolled in this study. The participants were allocated into two groups, experimental and control groups. All participants completed a course designed to promote healthy behavior modification. The experimental group participants completed four modules through an online training course based on the CDIO model. The control group was given theoretical lectures on the same topic online. Health education competencies and clinical decision-making perceptions were assessed before and after the training. Statistical analysis was performed using IBM SPSS 28.0. Results A significant difference was observed between these two groups in their performance on the theoretical test (t = −2.291, P<0.05) and operational assessment (t = −6.415, P<0.01). The participants in the experimental group scored better than those in the control group. Post-test results indicated that students in the experimental group demonstrated significantly better health education competency (t = −3.601, P<0.01) and clinical decision-making perception (t = −3.726, P<0.01). Conclusion The study found that online courses based on the CDIO model are compelling. The study concluded that online classes are needed during the pandemic as it does not limit time and space. Nursing students can take their internship from anywhere as long as they can access the internet. Also, the study found that the online course was interactive and collaborative.

Stress, Burnout, and Coping Strategies of Frontline Nurses During the COVID-19 Epidemic in Wuhan and Shanghai, China.

Background: Nurses at the frontline of caring for COVID-19 patients might experience mental health challenges and supportive coping strategies are needed to reduce their stress and burnout. The aim of this study was to identify stressors and burnout among frontline nurses caring for COVID-19 patients in Wuhan and Shanghai and to explore perceived effective morale support strategies. Method: A cross-sectional survey was conducted in March 2020 among 110 nurses from Zhongshan Hospital, Shanghai, who were deployed at COVID-19 units in Wuhan and Shanghai. A COVID-19 questionnaire was adapted from the previous developed "psychological impacts of SARS" questionnaire and included stressors (31 items), coping strategies (17 items), and effective support measures (16 items). Burnout was measured with the Maslach Burnout Inventory. Results: Totally, 107 (97%) nurses responded. Participants mean age was 30.28 years and 90.7% were females. Homesickness was most frequently reported as a stressor (96.3%). Seven of the 17 items related to coping strategies were undertaken by all participants. Burnout was observed in the emotional exhaustion and depersonalization subscales, with 78.5 and 92.5% of participants presenting mild levels of burnout, respectively. However, 52 (48.6%) participants experienced a severe lack of personal accomplishment. Participants with longer working hours in COVID-19 quarantine units presented higher emotional exhaustion (OR = 2.72, 95% CI 0.02-5.42; p = 0.049) and depersonalization (OR = 1.14, 95% CI 0.10-2.19; p = 0.033). Participants with younger age experienced higher emotional exhaustion (OR = 2.96, 95% CI 0.11-5.82; p = 0.042) and less personal accomplishment (OR = 3.80, 95% CI 0.47-7.13; p = 0.033). Conclusions: Nurses in this study experienced considerable stress and the most frequently reported stressors were related to families. Nurses who were younger and those working longer shift-time tended to present higher burnout levels. Psychological support strategies need to be organized and implemented to improve mental health among nurses during the COVID-19 pandemic.

Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global crisis. There is no therapeutic treatment specific for COVID-19. It is highly desirable to identify potential antiviral agents against SARS-CoV-2 from existing drugs available for other diseases and thus repurpose them for treatment of COVID-19. In general, a drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. Here we report a virtual screening approach with accelerated free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions and its use in identifying drugs targeting SARS-CoV-2 main protease (Mpro). The accurate FEP-ABFE predictions were based on the use of a restraint energy distribution (RED) function, making the practical FEP-ABFE-based virtual screening of the existing drug library possible. As a result, out of 25 drugs predicted, 15 were confirmed as potent inhibitors of SARS-CoV-2 Mpro The most potent one is dipyridamole (inhibitory constant Ki = 0.04 µM) which has shown promising therapeutic effects in subsequently conducted clinical studies for treatment of patients with COVID-19. Additionally, hydroxychloroquine (Ki = 0.36 µM) and chloroquine (Ki = 0.56 µM) were also found to potently inhibit SARS-CoV-2 Mpro We anticipate that the FEP-ABFE prediction-based virtual screening approach will be useful in many other drug repurposing or discovery efforts.

Single-cell landscape of immunological responses in patients with COVID-19.

In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ effector-GNLY (granulysin), CD8+ effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.

Clinical outcome of standardized oxygen therapy nursing strategy in COVID-19.

BACKGROUND: Novel coronavirus pneumonia (COVID-19) has become a global pandemic. However, a technical standard for oxygen therapy nursing, as well as how this would improve clinical outcomes and symptoms, is yet to be explored. METHODS: From February 9, 2020, to March 31, 2020, 58 patients of confirmed COVID-19 were admitted to the 20th ward of the Eastern Branch, Renmin Hospital of Wuhan University. Fifteen patients who did not receive oxygen therapy and 13 patients who were transferred from other hospitals were excluded. The rest of the 30 patients that received standardized oxygen therapy in our unit were included in the study. Baseline characteristics, symptoms, and finger pulse oxygen saturation were collected during hospitalization. RESULTS: Clinical outcomes of the 30 patients were as follows: 27 patients (90.00%) were cured and discharged; 3 patients (10.00%) who continued to stay in hospital were stabilized with symptoms relieved. The fingertip oxygen saturation was 94.80%±3.49% at ICU admission and 97.8%±1.27% when transferred out of ICU after standardized oxygen therapy (P<0.005). The symptoms of dyspnea, fatigue, and muscle aches of the patients were improved when transferred out of ICU, compared with their condition when admitted to ICU (P<0.05). CONCLUSIONS: The standardized oxygen therapy nursing strategy for patients with COVID-19 emphasizes the nursing measurement, which focuses on the patient's oxygenation. It is led by nurses and starts oxygen therapy at an earlier stage. It not only improves the clinical outcomes of critical patients but also effectively reduces the infection risk of medical staff while emphasizing nursing quality management.

Application of the PDCA cycle for standardized nursing management in a COVID-19 intensive care unit.

BACKGROUND: Nursing quality is an integral part of health care quality and one of key performance indicators (KPIs) for health care management. The Plan-Do-Check-Act (PDCA) cycle is a management tool for continuous improvement of a business's products or processes. It can be applied to standardize nursing management and thus improve the nursing quality and increase the survival rate of patients. This study assessed the value of the PDCA cycle in standardizing nursing management in an intensive care unit (ICU) for patients with severe coronavirus disease 2019 (COVID-19). METHODS: The status quo of the ICU was analyzed, and the relevant issues and countermeasures were proposed. The PDCA cycle was applied to standardize the nursing management in the ICU. RESULTS: Nine measures were proposed and applied to improve the management of the COVID-19 ICU: defining the clean or contaminated areas, use of self-designed shoe storage cabinets, defining staff roles and responsibilities, establishing the staffing structure, staff training, placing items at fixed locations, improving shift handover, use of bulletin boards for listing key points, and use of reserved drugs cabinets. The virus contamination awareness, professional skills, awareness of duties and responsibilities, and quality and performance of nursing were remarkably improved 2 weeks after the implementation of the above countermeasures. CONCLUSIONS: The PDCA cycle helps to standardize nursing management in COVID-19 ICU by developing and applying effective nursing management approaches.

Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) in silico, which suppressed SARS-CoV-2 replication in vitro. In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers (P < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.