Entangling of Peptide Nanofibers Reduces the Invasiveness of SARS-CoV-2.

The viral spike (S) protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells, facilitating its entry and infection. Here, functionalized nanofibers targeting the S protein with peptide sequences of IRQFFKK, WVHFYHK and NSGGSVH, which are screened from a high-throughput one-bead one-compound screening strategy, are designed and prepared. The flexible nanofibers support multiple binding sites and efficiently entangle SARS-CoV-2, forming a nanofibrous network that blocks the interaction between the S protein of SARS-CoV-2 and the ACE2 on host cells, and efficiently reduce the invasiveness of SARS-CoV-2. In summary, nanofibers entangling represents a smart nanomedicine for the prevention of SARS-CoV-2.

[Demographic Variables, Perceived Work Stress, and Job Satisfaction as Predictors of Organizational Commitment in Nurses During the COVID-19 Pandemic].

BACKGROUND: Organizational commitment, defined in nursing as the degree to which nurses identify with the goals and direction of their hospital, affects the willingness of nurses to participate actively in work tasks. PURPOSE: This study was designed to explore the predictive value of demographic variables, perceived work stress, and job satisfaction with regard to organizational commitment in nurses. METHODS: This cross-sectional study used an internet survey that included the Stress Scale on COVID-19 Patient Care, McCloskey/Mueller Satisfaction Scale, and Organizational Commitment Scale to collect data from 189 nurses at a hospital in southern Taiwan. Data analysis was conducted using SPSS/Window 22.0. RESULTS: Societal support and job satisfaction were identified as the most significant predictors of organizational commitment during the COVID-19 pandemic, explaining 47% of the total variance in organizational commitment (F [17, 171] = 8.79, p < .001). Level of perceived work stress averaged 48.3 (SD = 15.4), which is slightly higher than the median, and was highest among the participants who were married and had young children. The stress was mainly associated with social isolation. Those participants with a bachelor's degree or higher, a monthly income >NT$70,000, or with children reported relatively higher levels of job satisfaction and organizational commitment. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results provide a valuable guide to hospital management. To strengthen the organizational commitment and work dedication of nurses and to minimize pandemic-related staff attrition hospital management should work to ensure their nurses receive sufficient societal support and are satisfied with their jobs.

Small molecule angiotensin converting enzyme inhibitors: A medicinal chemistry perspective.

Angiotensin-converting enzyme (ACE), a zinc metalloprotein, is a central component of the renin-angiotensin system (RAS). It degrades bradykinin and other vasoactive peptides. Angiotensin-converting-enzyme inhibitors (ACE inhibitors, ACEIs) decrease the formation of angiotensin II and increase the level of bradykinin, thus relaxing blood vessels as well as reducing blood volume, lowering blood pressure and reducing oxygen consumption by the heart, which can be used to prevent and treat cardiovascular diseases and kidney diseases. Nevertheless, ACEIs are associated with a range of adverse effects such as renal insufficiency, which limits their use. In recent years, researchers have attempted to reduce the adverse effects of ACEIs by improving the selectivity of ACEIs for structural domains based on conformational relationships, and have developed a series of novel ACEIs. In this review, we have summarized the research advances of ACE inhibitors, focusing on the development sources, design strategies and analysis of structure-activity relationships and the biological activities of ACE inhibitors.

Interdisciplinary collaboration and computer-assisted home healthcare referral in the emergency department: a retrospective cohort study.

AIM: Home healthcare (HHC) provides continuous care for disabled patients. However, HHC referral after the emergency department (ED) discharge remains unclear. Thus, this study aimed its clarification. METHODS: A computer-assisted HHC referral by interdisciplinary collaboration among emergency physicians, case managers, nurse practitioners, geriatricians, and HHC nurses was built in a tertiary medical center in Taiwan. Patients who had HHC referrals after ED discharge between February 1, 2020 and September 31, 2020, were recruited into the study. A non-ED HHC cohort who had HHC referrals after hospitalization from the ED was also identified. Comparison for clinical characteristics and uses of medical resources was performed between ED HHC and non-ED HHC cohorts. RESULTS: The model was successfully implemented. In total, 34 patients with ED HHC and 40 patients with non-ED HHC were recruited into the study. The female proportion was 61.8% and 67.5%, and the mean age was 81.5 and 83.7 years in ED HHC and non-ED HHC cohorts, respectively. No significant difference was found in sex, age, underlying comorbidities, and ED diagnoses between the two cohorts. The ED HHC cohort had a lower median total medical expenditure within 3 months (34,030.0 vs. 56,624.0 New Taiwan Dollars, p = 0.021) compared with the non-ED HHC cohort. Compared to the non-ED HHC cohort, the ED HHC cohort had a lower ≤ 1 month ED visit, ≤ 6 months ED visit, and ≤ 3 months hospitalization; however, differences were not significant. CONCLUSION: An innovative ED HHC model was successfully implemented. Further studies with more patients are warranted to investigate the impact.

Assessment of dental personal protective equipment (PPE) and the relationship between manual dexterity and dissemination of aerosol and splatter during the COVID-19 pandemic.

Background/purpose: Asymptomatic COVID-19 patients visit the dental clinic for routine treatment, during which, high-speed handpieces, and third-use sprayers can produce aerosols. We focused on the effect and possible inadequacy of personal protective equipment (PPE) while cleaning teeth and assessed whether doctors' proficiency was related to the range of spraying droplets. Materials and methods: Doctors were divided into three different groups: attending physicians, residents, and intern respectively. Each doctor treated 15 patients; each group comprised 30 patients. The dentists wore leg covers, shoe covers, medical masks, haircaps, full masks, waterproof barrier gowns, and gloves. Each patient was covered with a waterproof hole towel, and the upper edge was fixed to the patient's nose with a medical tape. After cleaning the teeth with water contained red pigment, the spattering distance and range of droplets were calculated. Concurrently, we examined whether there was any droplet contamination on the PPE. Results: With the exception of shoe covers, haircaps, and medical surgical masks, pigment splash marks were found on both the dentist and assistant's PPE. The interns performed cleaning for a significantly longer time than the residents and attending physicians, with a significant statistical difference (P < 0.05). The spatter distance for the interns was significantly larger than the residents (P < 0.05). Conclusion: It is recommended that the hole towel be centered on the patient's nose tip, at least larger than a radius of 54.9-64.5 cm. The dentist's proficiency did cause differences in the duration of teeth cleaning, which further affects the spatter distance.

Mortality and risk factors associated with pulmonary embolism in coronavirus disease 2019 patients: a systematic review and meta-analysis.

To determine, in patients with coronavirus disease 2019 (COVID-19) infection, the associations of pulmonary embolism (PE) with mortality and risk factors for PE as well as the therapeutic benefit of anticoagulant prophylaxis. Embase, PubMed, Cochrane controlled trials register, and Web of Science databases were searched from inception to October 10, 2020. We included all published trials on PE in patients diagnosed with COVID-19 with eligibility of the trials assessed following the PRISMA guidelines. Sixteen clinical trials with 5826 patients were eligible. There were significant associations of PE with the male gender [odd ratio (OR) = 1.59, 95% CI 1.28-1.97], mechanical ventilation (OR = 3.71, 95% CI 2.57-5.36), intensive care unit admission (OR = 2.99, 95% CI 2.11-4.23), circulating D-dimer [mean difference (MD) = 5.04 µg/mL, 95% CI 3.67-6.42) and CRP (MD = 1.97 mg/dL, 95% CI 0.58- 3.35) concentrations without significant correlation between PE and mortality (OR = 1.31, 95% CI 0.82-2.08) as well as other parameters or comorbidities. After omitting one trial with strict patient selection criteria for anticoagulant prophylaxis, significant prophylactic benefit was noted (OR = 0.31, 95% CI 0.1-0.91). Our findings identified the risk factors associated with PE in COVID-19 patients and supported the therapeutic benefit of anticoagulant prophylaxis against PE in this patient population.

Probable Causes and Risk Factors for Positive SARS-CoV-2 Testing in Recovered Patients: Evidence From Guangzhou, China.

Some patients retested positive for SARS-CoV-2 following negative testing results and discharge. However, the potential risk factors associated with redetectable positive testing results in a large sample of patients who recovered from COVID-19 have not been well-estimated. A total of 745 discharged patients were enrolled between January 30, 2020, and September 9, 2020, in Guangzhou, China. Data on the clinical characteristics, comorbidities, drug therapy, RT-PCR testing, and contact modes to close contacts were collected. Patients who tested positive for SARS-CoV-2 after discharge were confirmed by guidelines issued by China. The repositive rate in different settings was calculated. Among 745 discharged patients, 157 (21.1%; 95% CI, 18.2-24.0%) tested repositive and the repositive rate was 16.8% (95% CI, 14.1-24.0%) for nasopharyngeal swabs and 9.7% (95% CI, 7.0-12.5%) for anal swabs. Among them, 55 (35.0%) were asymptomatic, 15 (9.6%) had mild symptoms, 83 (52.9%) had moderate symptoms, and 4 (2.6%) had severe symptoms at the first admission. The days from discharge to repositivity was 8.0 (IQR, 8.0-14.0). Most repositive patients were without clinical symptoms, and lymphocyte cell counts were higher than before being discharged. The likelihood of repositive testing for SARS-CoV-2 RNA was significantly higher among patients who were of younger age (OR, 3.88; 95% CI, 1.74-8.66, 0-17 years old), had asymptomatic severity (OR, 4.36; 95% CI, 1.47-12.95), and did not have clinical symptoms (OR, 1.89; 95% CI, 1.32-2.70, without fever). No other positive patients emerged within the families or close contacts of repositive patients. Our findings support prolonged but intermittent viral shedding as the probable cause for this phenomenon; we need to familiarize with the possibility that the virus will remain endemic.

Reverse Transcription Recombinase-Aided Amplification Assay With Lateral Flow Dipstick Assay for Rapid Detection of 2019 Novel Coronavirus.

Background: The emerging Coronavirus Disease-2019 (COVID-19) has challenged the public health globally. With the increasing requirement of detection for SARS-CoV-2 outside of the laboratory setting, a rapid and precise Point of Care Test (POCT) is urgently needed. Methods: Targeting the nucleocapsid (N) gene of SARS-CoV-2, specific primers, and probes for reverse transcription recombinase-aided amplification coupled with lateral flow dipstick (RT-RAA/LFD) platform were designed. For specificity evaluation, it was tested with human coronaviruses, human influenza A virus, influenza B viruses, respiratory syncytial virus, and hepatitis B virus, respectively. For sensitivity assay, it was estimated by templates of recombinant plasmid and pseudovirus of SARS-CoV-2 RNA. For clinical assessment, 100 clinical samples (13 positive and 87 negatives for SARS-CoV-2) were tested via quantitative reverse transcription PCR (RT-qPCR) and RT-RAA/LFD, respectively. Results: The limit of detection was 1 copies/µl in RT-RAA/LFD assay, which could be conducted within 30 min at 39°C, without any cross-reaction with other human coronaviruses and clinical respiratory pathogens. Compared with RT-qPCR, the established POCT assay offered 100% specificity and 100% sensitivity in the detection of clinical samples. Conclusion: This work provides a convenient POCT tool for rapid screening, diagnosis, and monitoring of suspected patients in SARS-CoV-2 endemic areas.

Maximum chest CT score is associated with progression to severe illness in patients with COVID-19: a retrospective study from Wuhan, China.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic is a world-wide health crisis. Limited information is available regarding which patients will experience more severe disease symptoms. We evaluated hospitalized patients who were initially diagnosed with moderate COVID-19 for clinical parameters and radiological feature that showed an association with progression to severe/critical symptoms. METHODS: This study, a retrospective single-center study at the Central Hospital of Wuhan, enrolled 243 patients with confirmed COVID-19 pneumonia. Forty of these patients progressed from moderate to severe/critical symptoms during follow up. Demographic, clinical, laboratory, and radiological data were extracted from electronic medical records and compared between moderate- and severe/critical-type symptoms. Univariable and multivariable logistic regressions were used to identify the risk factors associated with symptom progression. RESULTS: Patients with severe/critical symptoms were older (p < 0.001) and more often male (p = 0.046). A combination of chronic obstructive pulmonary disease (COPD) and high maximum chest computed tomography (CT) score was associated with disease progression. Maximum CT score (> 11) had the greatest predictive value for disease progression. The area under the receiver operating characteristic curve was 0.861 (95% confidence interval: 0.811-0.902). CONCLUSIONS: Maximum CT score and COPD were associated with patient deterioration. Maximum CT score (> 11) was associated with severe illness.

Robust 2D Otsu's Algorithm for Uneven Illumination Image Segmentation.

Otsu's algorithm is one of the most well-known methods for automatic image thresholding. 2D Otsu's method is more robust compared to 1D Otsu's method. However, it still has limitations on salt-and-pepper noise corrupted images and uneven illumination images. To alleviate these limitations and improve the overall performance, here we propose an improved 2D Otsu's algorithm to increase the robustness to salt-and-pepper noise together with an adaptive energy based image partition technology for uneven illumination image segmentation. Based on the partition method, two schemes for automatic thresholding are adopted to find the best segmentation result. Experiments are conducted on both synthetic and real world uneven illumination images as well as real world regular illumination cell images. Original 2D Otsu's method, MAOTSU_2D, and two latest 1D Otsu's methods (Cao's method and DVE) are included for comparisons. Both qualitative and quantitative evaluations are introduced to verify the effectiveness of the proposed method. Results show that the proposed method is more robust to salt-and-pepper noise and acquires better segmentation results on uneven illumination images in general without compromising its performance on regular illumination images. For a test group of seven real world uneven illumination images, the proposed method could lower the ME value by 15% and increase the DSC value by 10%.

Development of a clinical decision support system for severity risk prediction and triage of COVID-19 patients at hospital admission: an international multicentre study.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has globally strained medical resources and caused significant mortality. OBJECTIVE: To develop and validate a machine-learning model based on clinical features for severity risk assessment and triage for COVID-19 patients at hospital admission. METHOD: 725 patients were used to train and validate the model. This included a retrospective cohort from Wuhan, China of 299 hospitalised COVID-19 patients from 23 December 2019 to 13 February 2020, and five cohorts with 426 patients from eight centres in China, Italy and Belgium from 20 February 2020 to 21 March 2020. The main outcome was the onset of severe or critical illness during hospitalisation. Model performances were quantified using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion matrix. RESULTS: In the retrospective cohort, the median age was 50 years and 137 (45.8%) were male. In the five test cohorts, the median age was 62 years and 236 (55.4%) were male. The model was prospectively validated on five cohorts yielding AUCs ranging from 0.84 to 0.93, with accuracies ranging from 74.4% to 87.5%, sensitivities ranging from 75.0% to 96.9%, and specificities ranging from 55.0% to 88.0%, most of which performed better than the pneumonia severity index. The cut-off values of the low-, medium- and high-risk probabilities were 0.21 and 0.80. The online calculators can be found at www.covid19risk.ai. CONCLUSION: The machine-learning model, nomogram and online calculator might be useful to access the onset of severe and critical illness among COVID-19 patients and triage at hospital admission.

Survey on perceived work stress and its influencing factors among hospital staff during the COVID-19 pandemic in Taiwan.

This study aimed to investigate the perceived work stress and its influencing factors among hospital staff during the novel coronavirus (COVID-19) pandemic in Taiwan. A web-based survey was conducted at one medical center and two regional hospitals in southern Taiwan, targeting physicians, nurses, medical examiners, and administrators. The questionnaire included items on the demographic characteristics of hospital staff and a scale to assess stress among healthcare workers caring for patients with a highly infectious disease. A total of 752 valid questionnaires were collected. The hospital staff reported a moderate level of stress and nurses had a highest level of stress compared to staff in the other three occupational categories. The five highest stress scores were observed for the items "rough and cracked hands due to frequent hand washing and disinfectant use," "inconvenience in using the toilet at work," "restrictions on eating and drinking at work," "fear of transmitting the disease to relatives and friends," and "fear of being infected with COVID-19." Discomfort caused by protective equipment was the major stressor for the participants, followed by burden of caring for patients. Among participants who experienced severe stress (n = 129), work stress was higher among those with rather than without minor children. The present findings may serve as a reference for future monitoring of hospital staff's workload, and may aid the provision of support and interventions.

Contact Settings and Risk for Transmission in 3410 Close Contacts of Patients With COVID-19 in Guangzhou, China : A Prospective Cohort Study.

BACKGROUND: Risk for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to close contacts of infected persons has not been well estimated. OBJECTIVE: To evaluate the risk for transmission of SARS-CoV-2 to close contacts in different settings. DESIGN: Prospective cohort study. SETTING: Close contacts of persons infected with SARS-CoV-2 in Guangzhou, China. PARTICIPANTS: 3410 close contacts of 391 index cases were traced between 13 January and 6 March 2020. Data on the setting of the exposure, reverse transcriptase polymerase chain reaction testing, and clinical characteristics of index and secondary cases were collected. MEASUREMENT: Coronavirus disease 2019 (COVID-19) cases were confirmed by guidelines issued by China. Secondary attack rates in different settings were calculated. RESULTS: Among 3410 close contacts, 127 (3.7% [95% CI, 3.1% to 4.4%]) were secondarily infected. Of these 127 persons, 8 (6.3% [CI, 2.1% to 10.5%]) were asymptomatic. Of the 119 symptomatic cases, 20 (16.8%) were defined as mild, 87 (73.1%) as moderate, and 12 (10.1%) as severe or critical. Compared with the household setting (10.3%), the secondary attack rate was lower for exposures in health care settings (1.0%; odds ratio [OR], 0.09 [CI, 0.04 to 0.20]) and on public transportation (0.1%; OR, 0.01 [CI, 0.00 to 0.08]). The secondary attack rate increased with the severity of index cases, from 0.3% (CI, 0.0% to 1.0%) for asymptomatic to 3.3% (CI, 1.8% to 4.8%) for mild, 5.6% (CI, 4.4% to 6.8%) for moderate, and 6.2% (CI, 3.2% to 9.1%) for severe or critical cases. Index cases with expectoration were associated with higher risk for secondary infection (13.6% vs. 3.0% for index cases without expectoration; OR, 4.81 [CI, 3.35 to 6.93]). LIMITATION: There was potential recall bias regarding symptom onset among patients with COVID-19, and the symptoms and severity of index cases were not assessed at the time of exposure to contacts. CONCLUSION: Household contact was the main setting for transmission of SARS-CoV-2, and the risk for transmission of SARS-CoV-2 among close contacts increased with the severity of index cases. PRIMARY FUNDING SOURCE: Guangdong Province Higher Vocational Colleges and Schools Pearl River Scholar Funded Scheme.

Implications of the virus-encoded miRNA and host miRNA in the pathogenicity of SARS-CoV-2 (preprint)

The outbreak of COVID-19 caused by SARS-CoV-2 has rapidly spread worldwide and has caused over 1,400,000 infections and 80,000 deaths. There are currently no drugs or vaccines with proven efficacy for its prevention and little knowledge was known about the pathogenicity mechanism of SARS-CoV-2 infection. Previous studies showed both virus and host-derived MicroRNAs (miRNAs) played crucial roles in the pathology of virus infection. In this study, we use computational approaches to scan the SARS-CoV-2 genome for putative miRNAs and predict the virus miRNA targets on virus and human genome as well as the host miRNAs targets on virus genome. Furthermore, we explore miRNAs involved dysregulation caused by the virus infection. Our results implicated that the immune response and cytoskeleton organization are two of the most notable biological processes regulated by the infection-modulated miRNAs. Impressively, we found hsa-miR-4661-3p was predicted to target the S gene of SARS-CoV-2, and a virus-encoded miRNA MR147-3p could enhance the expression of TMPRSS2 with the function of strengthening SARS-CoV-2 infection in the gut. The study may provide important clues for the mechisms of pathogenesis of SARS-CoV-2.