Bioactive compounds of Jingfang Granules against SARS-CoV-2 virus proteases 3CLpro and PLpro.

OBJECTIVE: Jingfang Granules have been recommended for the prevention and treatment of corona virus disease 2019 (COVID-19). Through chemical analysis and bioactivity evaluation, this study aims to elucidate the potential effective components of Jingfang Granules. METHOD(S): The inhibitory acti-vities of Jingfang Granules extract against 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro), spike protein receptor-binding domain (S-RBD) and human cyclooxygenase-2 (COX-2) were evaluated using enzyme assay. The antitussive effects were evaluated using the classical ammonia-induced cough model. The chemical constituents of Jingfang Granules were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry (LC/MS). The 3CLpro and PLpro inhibitory activities of the major compounds were determined by enzyme assay, molecular docking, and site-directed mutagenesis. RESULT(S): Jingfang Granules exhibited 3CLpro and PLpro inhibitory activities, as well as COX-2 inhibitory and antitussive activities. By investigating the MS/MS behaviors of reference standards, a total of fifty-six compounds were characterized in Jingfang Granules. Sixteen of them were unambiguously identified by comparing with reference standards. The contents of the 16 major compounds were also determined, and their total contents were 2 498.8 mug/g. Naringin, nodakenin and neohesperidin were three dominating compounds in Jingfang Granules, and their contents were 688.8, 596.4 and 578.7 mug/g, respectively. In addition, neohesperidin and naringin exhibited PLpro inhibitory activities, and the inhibition rates at 8 mumol/L were 53.5% and 46.1%, respectively. Prim-O-glucosylcimifugin showed significant inhibitory activities against 3CLpro and PLpro, and the inhibitory rates at 8 mumol/L were 76.8% and 78.2%, respectively. Molecular docking indicated that hydrogen bonds could be formed between prim-O-glucosylcimifugin and amino acid residues H163, E166, Q192, T190 of 3CLpro (binding energy, -7.7 kcal/mol) and K157, D164, R166, E167, T301 of PLpro(-7.3 kcal/mol), respectively. Site-directed mutagenesis indicated amino acid residue K157 was a key active site for the interaction between prim-O-glucosylcimifugin and PLpro. CONCLUSION(S): Prim-O-glucosylcimifugin, neohesperidin, and naringin as the major compounds from Jingfang Granules could inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus proteases 3CLpro and PLpro. The results are valuable for rational clinical use of Jingfang Granules.

Mental health status of college students during coronavirus disease 2019 epidemic.

Objective To investigate the psychological characteristics of college students during the outbreak of coronavirus disease 2019 (COVID-19), so as to provide a basis for psychological intervention. Methods From May 17, 2020 to Jun. 17, 2020, the adjusted psychological questionnaires for emergent events of public health (PQEEPH) was surveyed among the college students of Beijing Union University. The questionnaire included 5 dimensions: depression, neurasthenia, fear, obsessive-compulsive anxiety, and hypochondriasis. Four grades were scored according to the degree and frequency of emotional responses: 0 means no symptoms, 1 means mild symptoms, 2 means moderate symptoms, and 3 means severe symptoms. Results A total of 3 019 valid questionnaires were collected. During the COVID-19 epidemic, the emotional responses of college students, from the most serious to the least, were fear, neurasthenia, depression, obsessive-compulsive anxiety, and hypochondriasis, with the incidences being 87.7% (2 648/3 019), 44.8% (1 353/3 019), 37.4% (1 129/3 019), 17.3% (522/3 019), and 11.6% (350/3 019), respectively. The fear scores of female students were higher than those of male students (P<0.001), the fear scores of college students from towns/suburbs were higher than those from rural and urban areas (both P<0.017), the scores of depression, neurasthenia and obsessive-compulsive anxiety of college students with confirmed COVID-19 cases around them or their relatives participated in the epidemic prevention and control as medical staff or logistics support personnel were higher than those without such conditions (all P<0.017), and the scores of depression, obsessive-compulsive anxiety and hypochondriasis of college students with suspected COVID-19 cases around them were higher than those without such condition (all P<0.017). Females were more likely to have moderate to severe fear than males (odds ratioOR=1.53, 95% confidence intervalCI1.25-1.88, P<0.001), those with confirmed or suspected COVID-19 cases around them were more likely to have moderate to severe fear than those without such conditions (OR=2.03, 95% CI 1.29-3.20, P=0.002), and those living in towns/suburbs were more likely to have moderate to severe fear than those living in rural and urban areas (OR=0.72, 95% CI 0.56-0.94, P=0.015;OR=0.78, 95% CI 0.63-0.97, P=0.025). Conclusion COVID-19 epidemic has impact on the psychology of college students. It is necessary to pay attention to the mental health of college students and provide targeted psychological counseling for them.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Mental health status of college students during coronavirus disease 2019 epidemic

Objective To investigate the psychological characteristics of college students during the outbreak of coronavirus disease 2019 (COVID-19), so as to provide a basis for psychological intervention. Methods From May 17, 2020 to Jun. 17, 2020, the adjusted psychological questionnaires for emergent events of public health (PQEEPH) was surveyed among the college students of Beijing Union University. The questionnaire included 5 dimensions: depression, neurasthenia, fear, obsessive-compulsive anxiety, and hypochondriasis. Four grades were scored according to the degree and frequency of emotional responses: 0 means no symptoms, 1 means mild symptoms, 2 means moderate symptoms, and 3 means severe symptoms. Results A total of 3 019 valid questionnaires were collected. During the COVID-19 epidemic, the emotional responses of college students, from the most serious to the least, were fear, neurasthenia, depression, obsessive-compulsive anxiety, and hypochondriasis, with the incidences being 87.7% (2 648/3 019), 44.8% (1 353/3 019), 37.4% (1 129/3 019), 17.3% (522/3 019), and 11.6% (350/3 019), respectively. The fear scores of female students were higher than those of male students (P<0.001), the fear scores of college students from towns/suburbs were higher than those from rural and urban areas (both P<0.017), the scores of depression, neurasthenia and obsessive-compulsive anxiety of college students with confirmed COVID-19 cases around them or their relatives participated in the epidemic prevention and control as medical staff or logistics support personnel were higher than those without such conditions (all P<0.017), and the scores of depression, obsessive-compulsive anxiety and hypochondriasis of college students with suspected COVID-19 cases around them were higher than those without such condition (all P<0.017). Females were more likely to have moderate to severe fear than males (odds ratio[OR]=1.53, 95% confidence interval[CI]1.25-1.88, P<0.001), those with confirmed or suspected COVID-19 cases around them were more likely to have moderate to severe fear than those without such conditions (OR=2.03, 95% CI 1.29-3.20, P=0.002), and those living in towns/suburbs were more likely to have moderate to severe fear than those living in rural and urban areas (OR=0.72, 95% CI 0.56-0.94, P=0.015;OR=0.78, 95% CI 0.63-0.97, P=0.025). Conclusion COVID-19 epidemic has impact on the psychology of college students. It is necessary to pay attention to the mental health of college students and provide targeted psychological counseling for them.Copyright © 2022, Second Military Medical University Press. All rights reserved.

Impacts of COVID-19 on financial markets: from the perspective of financial stress

This research analyzes the impacts of COVID-19 on financial markets from the perspective of financial stress. Effects on financial stress and its cross-border spillovers are investigated, respectively. The results show that the stress of a country's financial system is positively correlated with the severity of COVID-19 pandemic the country experiences. Although the volatilities of financial stress increased slightly, the cross-border spillovers have increased significantly after the COVID-19 outbreak. We provide a new insight to the impacts of the COVID-19 and suggest a more prudent look at financial risk management. © 2021 Informa UK Limited, trading as Taylor & Francis Group.

Digital Twin for Transportation Big Data: A Reinforcement Learning-Based Network Traffic Prediction Approach

Vehicular Ad-Hoc Networks (VANETs), as the crucial support of Intelligent Transportation Systems (ITS), have received great attention in recent years. With the rapid development of VANETs, various services have generated a great deal of data that can be used for transportation planning and safe driving. Especially, with the advent of Coronavirus Disease 2019 (COVID-19), the transportation system has been impacted, thus novel modes of transportation planning and intelligent applications are necessary. Digital twins can provide powerful support for artificial intelligence applications in Transportation Big Data (TBD). The features of VANETs are varying, which arises the main challenge of digital twins applying in TBD. Network traffic prediction, as part of digital twins, is useful for network management and security in VANETs, such as network planning and anomaly detection. This paper proposes a network traffic prediction algorithm aiming at time-varying traffic flows with a large number of fluctuations. This algorithm combines Deep Q-Learning (DQN) and Generative Adversarial Networks (GAN) for network traffic feature extraction. DQN is leveraged to carry out network traffic prediction, in which GAN is involved to represent Q-network. Meanwhile, the generative network can increase the number of samples to improve the prediction error. We evaluate the performance of our method by implementing it on three real network traffic data sets. Finally, we compare the two state-of-the-art competing methods with our method. IEEE

No, I Do Belong: How Asian American and Asian Canadian Professionals Defy and Counter Workplace Racial Violence during COVID-19

We explore the different types of racial violence encountered by Asian American and Asian Canadians (whom we refer to as Asians) in the workplace during COVID-19 and how they respond. Using a grounded theory approach, we found that during the COVID-19 pandemic, Asians experienced different types of workplace racial violence, most of which manifested as microaggressions, including a revival of the yellow peril trope, physical manifestations of bordering behaviour, and identity denial. In some cases, manifestations of physical violence also emerged. The data revealed that Asians demonstrated various types of agentic responses to challenge and counter unwanted and incorrect identities conveyed by the racial microaggressions. We enhance theory by shedding light on the experiences of Asians whose voice has largely been ignored in the organizational literature. Our study draws together and contributes to the theory on racial violence and racialized identity by highlighting the different types of racial violence faced by Asians and exploring the challenges they encounter in the face of racial microaggressions. Finally, we discuss practical implications of our study results and offer insight into how organizations can help support their Asian employees.

Analysis of antifungal use from 2015 – 2021 in a tertiary care cardiopulmonary hospital: the impact of the COVID-19 pandemic on antifungal prescribing practices

Introduction and ObjectivesUnderstanding the trends in antifungal prescribing patterns within a hospital is crucial for providing benchmarking data to implement targeted antifungal stewardship programmes in the future. Currently, there is little reported data on the trends and variations in antifungal prescribing practices within hospital trusts in the UK, particularly on antifungal usage in COVID-19 patients. This study aimed to analyse and compare the trends in antifungal usage from 2015 to 2021 within a cardiopulmonary tertiary care hospital in London, including assessing the impact of the COVID-19 pandemic on antifungal prescribing patterns. In addition, we aimed to assess whether the utilisation of antifungal agents in COVID-19 patients adhered to national guidelines.MethodAntifungal drug consumption data of 41161 patients was retrospectively analysed using 1.5 million electronic health records from a 312-bed tertiary care cardiopulmonary specialist hospital between 2015–2021. All data was administered and analysed using Python 3.0 software.ResultsOverall, total systemic antifungal usage between 2015–2021 increased by 55.36% however decreased between 2019–2021 by 19.4% within the COVID-19 pandemic. Antifungal „prescribing patterns in COVID-19 patients resembled general antifungal prescribing patterns previously within critical care, with liposomal amphotericin the most utilised antifungal agent differing from national and international management guidelines for COVID-19 associated pulmonary aspergillosis (1). In COVID-19 patients, 45.90% were given antifungals based on positive diagnostic data whereas 20.40% received empirical therapy.ConclusionOverall, antifungal usage during the COVID-19 pandemic in a specialist cardiorespiratory hospital reduced. Antifungal prescribing patterns within critical care were continued during the COVID-19 pandemic rather than adherence to national guidelines. Use of real-time clinical informatic data can be helpful to tailor antifungal stewardship programmes to help optimise prescribing. Current ongoing work will integrate an additional dataset on antifungal consumption from a second 950-bed tertiary care hospital in London, to analyse the variations in antifungal prescribing patterns between hospitals.ReferenceKoehler P, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infectious Diseases. 2021;21(6):e149–62.Please refer to page A214 for declarations of interest related to this .

[Bioactive compounds of Jingfang Granules against SARS-CoV-2 virus proteases 3CL(pro) and PL(pro)]

OBJECTIVE: Jingfang Granules have been recommended for the prevention and treatment of corona virus disease 2019 (COVID-19). Through chemical analysis and bioactivity evaluation, this study aims to elucidate the potential effective components of Jingfang Granules. METHODS: The inhibitory acti-vities of Jingfang Granules extract against 3-chymotrypsin-like protease (3CL(pro)), papain like protease (PL(pro)), spike protein receptor-binding domain (S-RBD) and human cyclooxygenase-2 (COX-2) were evaluated using enzyme assay. The antitussive effects were evaluated using the classical ammonia-induced cough model. The chemical constituents of Jingfang Granules were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry (LC/MS). The 3CL(pro) and PL(pro) inhibitory activities of the major compounds were determined by enzyme assay, molecular docking, and site-directed mutagenesis. RESULTS: Jingfang Granules exhibited 3CL(pro) and PL(pro) inhibitory activities, as well as COX-2 inhibitory and antitussive activities. By investigating the MS/MS behaviors of reference standards, a total of fifty-six compounds were characterized in Jingfang Granules. Sixteen of them were unambiguously identified by comparing with reference standards. The contents of the 16 major compounds were also determined, and their total contents were 2 498.8 μg/g. Naringin, nodakenin and neohesperidin were three dominating compounds in Jingfang Granules, and their contents were 688.8, 596.4 and 578.7 μg/g, respectively. In addition, neohesperidin and naringin exhibited PL(pro) inhibitory activities, and the inhibition rates at 8 μmol/L were 53.5% and 46.1%, respectively. Prim-O-glucosylcimifugin showed significant inhibitory activities against 3CL(pro) and PL(pro), and the inhibitory rates at 8 μmol/L were 76.8% and 78.2%, respectively. Molecular docking indicated that hydrogen bonds could be formed between prim-O-glucosylcimifugin and amino acid residues H163, E166, Q192, T190 of 3CL(pro) (binding energy, -7.7 kcal/mol) and K157, D164, R166, E167, T301 of PL(pro)(-7.3 kcal/mol), respectively. Site-directed mutagenesis indicated amino acid residue K157 was a key active site for the interaction between prim-O-glucosylcimifugin and PL(pro). CONCLUSION: Prim-O-glucosylcimifugin, neohesperidin, and naringin as the major compounds from Jingfang Granules could inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus proteases 3CL(pro) and PL(pro). The results are valuable for rational clinical use of Jingfang Granules.

REMDESIVIR TREATMENT for COVID-19 in HOSPITALIZED CHILDREN: CARAVAN INTERIM RESULTS

Background: Remdesivir (RDV) has been shown to shorten time to recovery in hospitalized adults with COVID-19. Some children who develop COVID-19 require hospitalization. Here we characterize the safety profile of RDV in 53 pediatric patients age 28 days to <18 years and describe clinical and virologic outcomes. Methods: CARAVAN (NCT04431453) is an ongoing open-label, single arm study of RDV in hospitalized patients <18 years with PCR-confirmed COVID-19. IV RDV was given for up to 10 days: 200mg on Day 1 followed by 100mg daily in Cohort 1 and 8 (<18y, weight ≥40kg) or 5mg/kg on Day 1 followed by 2.5mg/kg daily in Cohorts 2-4 (28 days to <18y, stratified by weight). Safety was assessed by adverse events (AEs) and lab tests (hematology, chemistry, urine, inflammatory, coagulation). Clinical outcomes included improvement on a 7-point ordinal scale, time to discharge, and oxygenation modality. Virologic outcomes included days to confirmed negative SARS-CoV-2 PCR (defined as 2 consecutive negative results). Results: At enrollment, median (IQR) age was 7y (2, 12) and weight was 24.6 (12.8, 55.1) Kg, 57% were female, 76% required supplemental oxygen, including 23% on invasive ventilation and 34% on high-flow oxygen (Table). Median number of RDV doses was 5 (4,8). Most patients (72%) experienced ≥1 AE;most common was constipation (17%). Serious AEs were reported for 21% of patients and none were study-drug related. Two patients with baseline transaminitis had non-serious AE of increased ALT contributing to premature discontinuation. Two patients died within the 30-day study period. Grade ≥ 3 lab abnormalities were reported in 42%;most common being decreased haemoglobin (n=9) and decreased eGFR levels (n=7). No safety trends related to RDV were apparent. In total, 85% showed clinical improvement on the 7-point ordinal scale by last assessment. Median (IQR) time to discharge was 8 (5, 17) days. By last assessment, 8% required supplemental oxygen, all of whom were invasively ventilated. Time to confirmed negative SARS-CoV-2 PCR CoV-2 PCR was 5 and 7 days from nasal/oropharyngeal samples in cohort 2 and 3, respectively, and not estimable in the other cohorts. Conclusion:RDV was safe and well tolerated among children 28 days to <18y treated for COVID-19. Overall, no safety trends for RDV were apparent and a high proportion, 85%, had clinical improvement. The study is ongoing with enrolment of full term and preterm neonates pending dose determination.

A preliminary study of post-traumatic stress symptoms of two confirmed and six suspected Coronavirus disease 2019 patients

Objective To explore the psychological status and interventions in confirmed and suspected Coronavirus disease 2019 (COVID-19) patients. Methods The data of 2 confirmed cases and 6 suspected cases of COVID-19 were collected through the Internet. Demographic data of the patients were collected by self-designed self-assessment general situation questionnaire. Post-traumatic stress symptoms were assessed by post-traumatic stress disorder checklist for DSM-5 (PCL-5). Sleep quality was evaluated by Pittsburgh sleep quality index. Results There were 5 females and 3 males aged from 17 to 71 years old. The education level was junior college, bachelor degree and above in 7 patients, and senior high school or below in one patient. Five cases had the contact history with Wuhan residents. The screening result of post-traumatic stress symptom was positive in one confirmed case and one suspected case. Invasive symptoms presented in 5 cases. The epidemic affected the sleep quality of 8 patients in different degrees, mainly manifested as sleep fitfully at night or early morning awakening (5 cases). The total score of PCL-5 was consistent with the change trend of sleep quality. The higher the total score of PCL-5, and the worse the sleep quality. Conclusion Confirmed and suspected COVID-19 patients have sleep disorders (sleep fitfully at night or early morning awakening) and psychological trauma (invasive symptoms), and they need timely and effective psychological interventions.

Safety and efficacy of remdesivir in a pediatric covid-19 population

Background: COVID-19 is generally a mild disease in children and infants. However, a small proportion develop severe disease requiring intensive care and ventilatory support. Remdesivir (RDV), a direct-acting nucleotide pro-drug inhibitor of viral RNA-dependent RNA polymerases, has been shown to shorten time to recovery in adults with severe COVID-19. The aim of this study is to evaluate the safety and efficacy of RDV in pediatric patients. Methods: CARAVAN (NCT04431453) is an ongoing open-label study of RDV in hospitalized pediatric patients with PCR-confirmed COVID-19. IV RDV is given for up to 10 days: 200mg on Day 1 followed by 100mg daily in Cohort 1 (12 to <18y, weight ≥40kg) or 5mg/kg on Day 1 followed by 2.5mg/kg daily in Cohorts 2-4 (28 days to <18y, stratified by weight). Safety is assessed by adverse events (AEs) and laboratory tests. Efficacy assessments include change in oxygen requirements and clinical status on a 7-point ordinal scale through Day 10. Results: Preliminary results for the first 27 patients are presented. Median (range) age and weight were: Cohort 1, 15 (12-17)y and 84 (47-192)kg;Cohort 2, 8 (4-16)y and 27 (25-39)kg;Cohort 3, 3 (2-5)y and 16 (12-18)kg;Cohort 4, 6 (2-11)m and 7 (3-10)kg. Overall, 52% were <12y, 56% were female, and 96% had ≥1 comorbid medical condition. Median number of RDV doses was 5;most RDV discontinuations were due to clinical improvement. At baseline, 67% required supplemental oxygen, including 22% on invasive ventilation;at Day 10, the values were 26% and 15%, respectively. In total, 70% showed clinical improvement on the 7-point ordinal scale at Day 10. Most (78%) had ≥1 AE, including 17% with study drug-related AEs;7% discontinued study drug due to an AE. Serious AEs were reported for 33% of patients;no SAEs were study drug related. Two patients died within 30 days of completing treatment. Grade 3 or 4 lab abnormalities were reported in 52%;those reported in ≥1 patient were decreased hemoglobin (n=5), and hypoglycemia, glycosuria, and increased PTT (n=2 each). No safety trends related to RDV were apparent. Conclusion: Among pediatric patients aged 2m to 17y treated with RDV for COVID-19, 70% had clinical improvement. The study is ongoing;enrolment of full term and preterm neonates is pending determination of the dose to be evaluated.