RNA Interference Approach Is a Good Strategy against SARS-CoV-2.

COVID-19, caused by SARS-CoV-2, created a devastating outbreak worldwide and consequently became a global health concern. However, no verifiable, specifically targeted treatment has been devised for COVID-19. Several emerging vaccines have been used, but protection has not been satisfactory. The complex genetic composition and high mutation frequency of SARS-CoV-2 have caused an uncertain vaccine response. Small interfering RNA (siRNA)-based therapy is an efficient strategy to control various infectious diseases employing post-transcriptional gene silencing through the silencing of target complementary mRNA. Here, we designed two highly effective shRNAs targeting the conserved region of RNA-dependent RNA polymerase (RdRP) and spike proteins capable of significant SARS-CoV-2 replication suppression. The efficacy of this approach suggested that the rapid development of an shRNA-based therapeutic strategy might prove to be highly effective in treating COVID-19. However, it needs further clinical trials.

Clinical and laboratory predictors for disease progression in patients with COVID-19: A multi-center cohort study.

BACKGROUND: Reliable clinical and laboratory predictors of coronavirus disease 2019 (COVID-19) disease progression could help to identify the subset of patients who are susceptible to severe symptoms. This study sought to identify the predictors for disease progression in patients with COVID-19. METHODS: This study recruited consecutive patients from four hospitals between March 1, 2020, and July 31, 2021. Demographic characteristics, laboratory results, and clinical outcomes were collected. RESULTS: Among the 239 enrolled patients, 39.3% (94/239) experienced in-hospital disease progression. Multivariate logistic regression revealed that coronary arterial disease (CAD) (OR,4.15;95% C.I., 1.47-11.66), cerebrovascular attack (CVA) (OR,12.98; 95% C.I., 1.30-129.51), platelet count < median value (OR, 3.23; 95% C.I., 1.65-6.32), and C-reactive protein (CRP) levels > median value of (OR, 2.25; 95% C.I., 1.02-4.99) were independent factors associated with COVID-19 progression. Patients who underwent disease progression at days 1, 4, and 7 presented lower lymphocyte counts and higher CRP levels, compared to patients without disease progression. CONCLUSIONS: The study revealed that in hospitalized COVID-19 patients, comorbidity with CAD and CVA, low platelet count, and elevated CRP levels were independently associated with disease progression. Compared with patients without disease progression, those with disease progression presented persistently low lymphocyte counts and elevated CRP levels.

Network characteristics and stock liquidity:Evidence from the UK

This article examines the effect of the Engle-Granger (E-G) price spillover network characteristics on firm's stock liquidity with a longitudinal dataset of FTSE 350 from 2006 to 2021. We find that the subprime crisis, European debt sovereign crisis, British Brexit and COVID-19 caused dramatic network structure change. We also find that firms with higher centrality are likely to suffer from more or greater price shocks leading to lower stock liquidity. Finally, the robust of our results has also been identified, and a general framework for network characteristics and stock liquidity has been established to some extent.

Phase separation-mediated condensation of N protein-deaminase complex promotes SARS-CoV-2 mutagenesis (preprint)

The emergence of SARS-CoV-2 variants poses enormous challenges to the prevention and control of COVID-19 with alterations in antigenicity, transmissibility and pathogenicity. The rapid evolution of RNA viruses could be caused by high mutation frequencies during replication, arising by replication errors, intergenomic recombination or even host deaminases. We sought to understand whether host deaminases are involved in SARS-CoV-2 mutation, and how they orchestrate host deaminases to trigger this process. Herein, we provided the experimental evidence that APOBEC and ADAR deaminases act as the driving forces for SARS-CoV-2 mutagenesis. Mechanistically, SARS-CoV-2 nucleocapsid (N) protein, which is responsible for packaging viral genomic RNA, complexes with host deaminases to facilitate viral RNA mutation. Moreover, N protein employs deaminases-involved condensates to further promote viral RNA mutation. Mutant N protein with F17A substitution, defective in entry of deaminases-involved RNA granules, leads to the decreased mutation of viral RNA, confirming the function of N protein-deaminase condensates on RNA editing. Our study sheds light on the novel mechanism of SARS-CoV-2 mutation during host-virus arms race.

A comprehensive analysis of the intervention of a fresh air ventilation system on indoor air quality in classrooms

Adequate classroom air quality is vital to student health and learning outcomes. Prolonged periods of air conditioner use in enclosed classrooms may result in poor air quality. However, opening classroom windows may expose students to air pollutants if the outdoor air quality is poor. This study investigated CO2 and PM2.5 concentrations in 86 classrooms installed with air conditioners in elementary and middle schools in southern Taiwan, each additionally installed with a fresh air ventilation system equipped with an E11-class filter. Enclosed air-conditioned classrooms generally have a CO2 concentration greater than 2500 ppm;occasionally, this figure reaches 3500 ppm. With the installed air ventilation system operating, mean classroom CO2 concentration decreased to 1084 ± 203 ppm, and the median CO2 concentration decreased to 1120 ppm. However, the CO2 concentrations of over half the classrooms remained higher than the concentration advised by the World Health Organization (1000 ppm). This high CO2 concentration was a result of the short distance (1.5–2 m) between the indoor air outlet and the recirculated air inlet resulting in a shortened circuit of air travel. Also, the initial filter installed over the indoor air outlet of the system reduced air penetration into the classroom. When the ventilation system was manually activated without activating the air conditioners, the median PM2.5 concentration measured at the indoor air outlet and the median classroom PM2.5 concentration were 2 μg/m3 and 20 μg/m3, respectively. This implied the presence of other sources of PM2.5 in classrooms, particularly ceiling and wall-mounted fans. The activation of these fans spread dust onto classroom furniture. Overall, fresh air ventilation systems providing filtered air improve classroom ventilation efficiency and indoor air quality by reducing CO2 and PM2.5 concentrations, but the cleanliness of fans and furniture must be maintained.

The Coping Strategies of School Administration and Teacher Teaching Under the COVID-19

The study aims to explore the coping strategies of school administration and teaching during the COVID-19 epidemic. The coping strategies of school administration include: 1. Accelerate the development of smart campuses;2. Exert the function of technology leadership to achieve highefficiency services;3. Implement the curriculum plan for the epidemic;4. Build the support system and improve measures;5. Utilize contingency and flexible alternative adapted to school conditions;6. Establish the mechanism for disadvantaged students and psychological counseling. The coping strategies of teaching mainly include: 1. Enhance professional quality of online teaching and establish online classroom principles;2. Identify the success factors of distance teaching and improve the motivation to learn;3. Enhance the efficiency of the integration of information into teaching and improve teachers' technological pedagogical and content knowledge;4. Strengthen the sense of value and IT literacy to face challenges;5. Improve the collective intelligence of the teacher to solve problems together;6. Unblock the communication channels among teachers, parents and students to seek the common good through collaborative work.

Insisting on Life Dignity: Advance Care Planning in Taiwan During COVID-19 Pandemic (preprint)

Background:The coronavirus disease 2019 (COVID-19) outbreak is a global public health crisis that has affected the implementation of advance care planning (ACP) in Taiwan. The purpose of this study is to (1) confirm that COVID-19 significantly reduced public participation in ACP, (2) identify factors influencing the implementation of ACP during the COVID-19 pandemic and how they differ from those before the COVID-19 outbreak.Methods: An observational study from retrospective review of medical chart and clinical information.This is a hospital-based study to examine the characteristics of ACP implementation in Taiwan during COVID-19. A total of 1,253 participants were recruited, including 916 people who had completed ACP from September through December 2019, and 337 people from January through April 2020.Results:This study representing an approximately 65% decrease in ACP participation after COVID-19 outbreak. The cancellation rate of ACP during COVID-19 is higher before outbreak. After COVID-19 outbreak, Participation rate of disadvantaged populations increased from 16.92% to 21.66%. The percentage of participants with caregiver experiences decreased from 31.66%to to 23.44% . Participants who did not wish for their families to bear decision-making responsibilities increased from 44.00% to 52.52%. The percentage of offspring participation increased from 86.57% to 90.80%. The percentage of individuals completing ACP after the outbreak without signing an advance directive increased from 5.57% to 9.20%. The COVID-19 pandemic significantly reduced participation in ACP. Conclusions: This study directly compared the ACP implementation before and after COVID-19, which is a tremendous global health crisis influencing the conceptions of life and death.COVID-19 has threatened the public’s health and has changed ACP in the healthcare system by increasing public awareness of the topic of death. After COVID-19, both medical staff and the public should clearly express their opinions on terminal care.Policy supports and active participation of medical team can encourage disadvantages to complete ACP.Healthcare workers should provide palliative and terminal care services in which patient comfort and dignity are the primary focus of care.Trial registration:This study was approved on 3 June 2020 by the Taipei City Hospital Institutional Review Board (Case No.: TCHIRB-10808008-E).

Tasks in Group Quarantine Centers in Relation to the Emotional Distress of Personnel the Experiences from COVID-19 Epidemic Prevention in Taiwan (preprint)

Background: In order to prevent COVID-19, Taiwan Central Epidemic Command Center established group quarantine centers in January 2020 to implement isolation and epidemic prevention. The task groups in the group quarantine centers included the safety, logistics, and health groups. The objectives of this study were to understand whether the emotional distresses of group quarantine centers personnel are disturbed under high-pressure work environment. Methods: A structured questionnaire was designed. Its content contained two parts: the first part collected the demographical information of the participants, and the second part was a scale named the Brief Symptom Rating Scale (BSRS-5). The data collected were entered and analyzed using IBM SPSS Statistics for Windows, Version 21.0, and the difference analysis among the three groups were conducted in terms of the variables (significance level p <0.05); related factors affecting emotional scores on the BSRS-5 were identified through multiple regression analysis. Results: The online questionnaires were filled out from August 6 to August 13, 2020, and a total of 155 staffs were analyzed further. The safety group was collected 70 staffs (45.2%), the health group was collected 57 staffs (36.8%) and the logistics group was collected 28 staffs (18.0%). According to the analysis we found that three important results. First, no positive cases of COVID-19 been screened, the personnel do not feel distressed on duty in group quarantine centers. Second, when a quarantine case is screened positive for COVID-19, it will increase staff's emotional distress in all three group and the odds ratio with a BSRS-5 score greater than or equal to 6 points is 4.53 times (OR=4.53, 95%CI: 1.83-11.21) of cases that have not been screened as positive. Final, Cases screened as positive did not cause emotional problems in retired personnel serving in group quarantine centers. Conclusion: In the face of COVID-19 disease, our government should not only take care of people in the community, but also protect and take care of the front-line epidemic prevention personnel. Our government should be understand the emotional distresses of personnel and provide counseling and care, so that personnel can continue to protect people of Taiwan during epidemic prevention.

A case of coronavirus disease 2019 with tuberculous meningitis / 中华神经科杂志

Novel coronavirus pneumonia, also known as coronavirus disease 2019 (COVID-19), is caused by a new coronavirus that infects the lungs. Although some patients with COVID-19 may be combined with neurological symptoms, there is no direct evidence that this new coronavirus can directly invade nerve system. A case of COVID-19 with tuberculous meningitis is reported to remind that when patients with COVID-19 present symptom of encephalitis or meningitis, a comprehensive pathogen examination is recommended.

A Cascaded Learning Strategy for Robust COVID-19 Pneumonia Chest X-Ray Screening (preprint)

We introduce a comprehensive screening platform for the COVID-19 (a.k.a., SARS-CoV-2) pneumonia. The proposed AI-based system works on chest x-ray (CXR) images to predict whether a patient is infected with the COVID-19 disease. Although the recent international joint effort on making the availability of all sorts of open data, the public collection of CXR images is still relatively small for reliably training a deep neural network (DNN) to carry out COVID-19 prediction. To better address such inefficiency, we design a cascaded learning strategy to improve both the sensitivity and the specificity of the resulting DNN classification model. Our approach leverages a large CXR image dataset of non-COVID-19 pneumonia to generalize the original well-trained classification model via a cascaded learning scheme. The resulting screening system is shown to achieve good classification performance on the expanded dataset, including those newly added COVID-19 CXR images.

A rapid screening model for early predicting novel coronavirus pneumonia in Zhejiang Province of China: A Multicenter Study (preprint)

Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from Jan 17 to Feb 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920 (95% confidence interval : 0.902-0.938; AUROC=0.915, and its standard deviation of 0.028, as evaluated in 5-fold cross-validation). At a value of whether the predicted score >4.0, the model could detect NCP with a specificity of 98.3%; at a cut-off value of < -0.5, the model could rule out NCP with a sensitivity of 97.9%. The study demonstrated that the rapid screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.

The IMPDH inhibitor merimepodib suppresses SARS-CoV-2 replication in vitro. (preprint)

The ongoing COVID-19 pandemic continues to pose a major public health burden around the world. The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over one million people worldwide as of April, 2020, and has led to the deaths of nearly 300,000 people. No approved vaccines or treatments in the USA currently exist for COVID-19, so there is an urgent need to develop effective countermeasures. The IMPDH inhibitor merimepodib (MMPD) is an investigational antiviral drug that acts as a noncompetitive inhibitor of IMPDH. It has been demonstrated to suppress replication of a variety of emerging RNA viruses. We report here that MMPD suppresses SARS-CoV-2 replication in vitro. After overnight pretreatment of Vero cells with 10 M of MMPD, viral titers were reduced by 4 logs of magnitude, while pretreatment for 4 hours resulted in a 3-log drop. The effect is dose-dependent, and concentrations as low as 3.3 M significantly reduced viral titers when the cells were pretreated prior to infection. The results of this study provide evidence that MMPD may be a viable treatment option for COVID-19.

Potent Antiviral Activities of Type I Interferons to SARS-CoV-2 Infection (preprint)

The historical outbreak of COVID-19 disease not only constitutes a global public health crisis, but also has a devastating social and economic impact. The disease is caused by a newly identified coronavirus, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). There is an urgent need to identify antivirals to curtail the COVID-19 pandemic. Herein, we report the remarkable sensitivity of SARS-CoV-2 to recombinant human interferons and {beta} (IFN/{beta}). Treatment with IFN- or IFN-{beta} at a concentration of 50 international units (IU) per milliliter drastically reduce viral titers by 3.4 log or 4.5 log, respectively in Vero cells. The EC50 of IFN- and IFN-{beta} treatment is 1.35 IU/ml and 0.76 IU/ml, respectively, in Vero cells. These results suggested that SARS-CoV-2 is more sensitive to many other human pathogenic viruses, including the SARS-CoV. Overall, our results demonstrate the potent efficacy of human Type I IFN in suppressing SARS-CoV-2 replication, a finding which could inform future treatment options for COVID-19.