Comprehensive Bioinformatics analysis of angiotensin-converting enzyme 2 (ACE2) (preprint)

ACE2, a member of the angiotensin converting enzyme family, plays an irreplaceable role in the renin-angiotensin system. And the variations of ACE2 are regarded as the key factor to human diseases such as the novel coronavirus pneumonia, cardiovascular disease, and tumors. Here, we summarized the mutation, expression, modification and function of the human ACE2 based on comprehensive bioinformatics analysis. Especially, the relationship between ACE2 expression and diseases, especially tumor was further discussed. ACE2 is highly conserved in different genera and families. We explored the correlation between ACE2 and disease based on the datasets of GCBI and GEO (Gene expression omnibus), and found the expression of ACE2 is related to heart failure. High prevalence of ACE2 mutations is observed in diffuse large B-cell lymphoma, uterine carcinosarcoma (UCS), and stomach adenocarcinoma (STAD). We first identified that highly expressed of ACE2 was linked to poor prognosis of overall survival for tumors of brain lower grade glioma (LGG). Specially, the expression level of ACE2 in kidney-related tumor tissues is much higher than that of normal kidney tissues. ACE2 is negatively correlated with the infiltration level of cancer-associated fibroblasts in most kinds of cancers, such as uterine corpus endometrial carcinoma (UCEC), esophageal carcinoma (ESCA), ovarian serous cystadenocarcinoma (OV) and kidney renal clear cell carcinoma (KIRC); positively correlation in testicular germ cell tumors (TGCT). The different phosphorylation sites of ACE2 were analyzed in CPTAC dataset, and the DNA methylation of ACE2 in colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), and rectum adenocarcinoma (READ) was lower than that of normal control by using SMART database. Moreover, we summarized the interaction proteins and targeted miRNAs of ACE2 through bioinformatics. Then we found the endocrine process and the regulation of systemic arterial blood pressure were involved in the functional mechanisms of ACE2 by using KEGG and GO analysis. Our study offers a relatively comprehensive understanding of ACE2.

Rapid development and mass production of SARS-CoV-2 neutralizing Chicken egg yolk antibodies with protective efficacy in hamsters (preprint)

Despite the record speed of developing vaccines and therapeutics against the SARS-CoV-2 virus, it is not a given that such success can be secured in future pandemics. In addition, COVID-19 vaccination and application of therapeutics remain low in developing countries. Rapid and low cost mass production of antiviral IgY antibodies could be an attractive alternative or complementary option for vaccine and therapeutic development. In this article, we rapidly produced SARS-CoV-2 antigens, immunized hens and purified IgY antibodies in 2 months after the SARS-CoV-2 gene sequence became public. We further demonstrated that the IgY antibodies competitively block RBD binding to ACE2, neutralize authentic SARS-CoV-2 virus and effectively protect hamsters from SARS-CoV-2 challenge by preventing weight loss and lung pathology, representing the first comprehensive study with IgY antibodies. The process of mass production can be easily implemented in most developing countries and hence could become a new vital option in our toolbox for combating viral pandemics. This study could stimulate further studies, optimization and potential applications of IgY antibodies as therapeutics and prophylactics for human and animals.

The effect of hindrance stressors on the emotional exhaustion among front-line healthcare workers in the recuperation period during the COVID-19 epidemic in China: a prospective cross-sectional study.

OBJECTIVES: This study aimed to examine the influence and conditioning process of hindrance stressors on the emotional exhaustion of the front-line healthcare workers during recuperation, examine the potential mediating process of rumination, and explore the moderating role of organisational and family factors. SETTING: This cross-sectional study was conducted during 12-20 July 2020. Total 418 questionnaires were collected from front-line healthcare workers by random cluster sampling. Hierarchical regression was performed to analyse the mediating effect of affective rumination using SPSS25.0, while PROCESS was used to further investigate the moderating role of servant leadership and family support. PARTICIPANTS: 418 healthcare workers were investigated randomly from front-line medical teams. Inclusion criteria included worked as front-line health workers and participated in the fight against COVID-19 in Hubei; age ≥18 years; normal cognitive and comprehension abilities under physical and mental health; volunteer to participate in this study. Exclusion criteria included recently affected by major events other than COVID-19 or those with a history of neurasthenia and trauma. RESULTS: Using descriptive analysis of average value and SD measured by a five-item scale (MBI-GS), we found that front-line healthcare workers' emotional exhaustion score (2.45±0.88) was at the medium level. Hindrance stressors, mediated by affective rumination, had a significant positive predictive effect on emotional exhaustion. Servant leadership negatively moderated the direct effect of hindrance stressors on emotional exhaustion (ß=-0.106, p<0.01). Family support positively moderated the impact of hindrance stressors on emotional exhaustion (ß=0.082, p<0.05). CONCLUSIONS: During the recuperation period, after successfully controlling COVID-19 at the front line, the first-line healthcare workers should be screened through affective rumination evaluation to gain insight for targeted interventions. We find that servant leadership is beneficial in alleviating emotional exhaustion while family support worsens emotional exhaustion. We suggest that servant leadership should be further promoted in medical organisations, and family support should be applied correctly and cautiously.

Network-Based Approach to Repurpose Approved Drugs for COVID-19 by Integrating GWAS and Text Mining Data

The coronavirus disease 19 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has a rapidly increasing prevalence and has caused significant morbidity/mortality. Despite the availability of many vaccines that can offer widespread immunization, it is also important to reach effective treatment for COVID-19 patients. However, the development of novel drug therapeutics is usually a time-consuming and costly process, and therefore, repositioning drugs that were previously approved for other purposes could have a major impact on the fight against COVID-19. Here, we first identified lung-specific gene regulatory/interaction subnetworks (COVID-19-related genes modules) enriched for COVID-19-associated genes obtained from GWAS and text mining. We then screened the targets of 220 approved drugs from DrugBank, obtained their drug-induced gene expression profiles in the LINCS database, and constructed lung-specific drug-related gene modules. By applying an integrated network-based approach to quantify the interactions of the COVID-19-related gene modules and drug-related gene modules, we prioritized 13 approved drugs (e.g., alitretinoin, clocortolone, terazosin, doconexent, and pergolide) that could potentially be repurposed for the treatment of COVID-19. These findings provide important and timely insights into alternative therapeutic options that should be further explored as COVID-19 continues to spread.

Analysis of Factors Influencing Stock Market Volatility Based on GARCH-MIDAS Model

This paper further extends the existing GARCH-MIDAS model to deal with the effect of microstructure noise in mixed frequency data. This paper has two highlights. First, according to the estimation of the long-term volatility components of the GARCH-MIDAS model, rAVGRV is adopted to substitute for the RV estimator. rAVGRV uses the rich data sources in tick-by-tick data and significantly corrects the impact of the microstructure noise on volatility estimation. Second, besides introducing macroeconomic variables (i.e., macroeconomic consistency index (MCI), deposits in financial institutions (DFI), industrial value-added (IVA), and M2), Chinese Economic Policy Uncertainty (CEPU) index and Infectious Disease Equity Market Volatility Tracker (EMV) are introduced in the long-run volatility component of the GARCH-MIDAS model. As indicated by the results of this paper, the rAVGRV-based GARCH-MIDAS is slightly better than the RV model-based GARCH-MIDAS. In addition to the common macroeconomic variables significantly impacting stock market volatility, CEPU also substantially impacts stock market volatility. Nevertheless, the effect of EMV on the stock market is insignificant.

Progress of study on biology, epidemiology and prevention strategies for SARS-CoV-2 lambda variant

The emergence of SARS-COV-2 caused the global pandemic crisis.As the pandemic evolves, the mutation of novel coronavirus genome continues, resulting in several novel coronavirus variants. For example, Alpha (B.1.1.7), Beta (B.1.351), Gamma (p.1), Delta (B.1.617.2) and Lambda (C.37) variants may cause changes in biological characteristics of the virus, such as pathogenicity and infectivity, which may lead immune escape from vaccine protection and antibodies, even bring greater harm to epidemic prevention and control and also disease treatment. In this paper, the pandemic characteristics and relevant prevention and control measures of lambda variant are reviewed.

Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial

Objective: To assess the efficacy and safety of hydroxychloroquine plus standard of care compared with standard of care alone in adults with coronavirus disease 2019 (covid-19). Design: Multicentre, open label, randomised controlled trial. Setting 16 government designated covid-19 treatment centres in China, 11 to 29 February 2020. Participants: 150 patients admitted to hospital with laboratory confirmed covid-19 were included in the intention to treat analysis (75 patients assigned to hydroxychloroquine plus standard of care, 75 to standard of care alone). Interventions Hydroxychloroquine administrated at a loading dose of 1200 mg daily for three days followed by a maintenance dose of 800 mg daily (total treatment duration: two or three weeks for patients with mild to moderate or severe disease, respectively). Main outcome measure: Negative conversion of severe acute respiratory syndrome coronavirus 2 by 28 days, analysed according to the intention to treat principle. Adverse events were analysed in the safety population in which hydroxychloroquine recipients were participants who received at least one dose of hydroxychloroquine and hydroxychloroquine non-recipients were those managed with standard of care alone.

The change of atmospheric ozone formation sensitivity in Fujian Province based on OMI satellite data during the period of COVID-19

Based on the OMI satellite data, the characteristics of atmospheric ozone sensitivity in Fujian province and its nice municipalities during the period of COVID-19 epidemic were assessed with HCHO and NO2 vertical column densities as proxies for ozone sensitivity. The results showed that Fujian Province was dominated by VOCs-limited regime before the pandemic with the controlled area proportion of 46.5%. The other two regimes: NOx-VOCs-limited regime and NOx-limited regime, controlled 25.0% and 28.5% of the area, respectively. The area proportion controlled by VOXs-limited regime was highest in Xiamen and lowest in Nanping. During the period with strict pandemic control policies, VOXs-limited regime, NOx-VOCs-limited regime and NOx-limited regime controlled 29.5%, 21.1%, and 49.4% of the area, respectively. The area proportion controlled by NOx-limited regime was highest in Ningde and lowest in Putian. During the stable period, VOXs-limited regime, NOx-VOCs-limited regime and NOx-limited regime controlled 23.1%, 29.1%, and 47.8% of the area, respectively. NOx-limited regime was the dominant regime with highest area proportion controlled in Nanping and lowest area proportion in Xiamen. Compared with the before pandemic period, the area proportion of Xiamen controlled by VOCs-limited regime was obviously reduced（38.1% less） during the period with strict control policies, and the lowest reduction was in Sanming with a moderate decrease of 7.9%. According to the conversion results, Putian, Quanzhou, and Xiamen were categorized into the first city group where changes in ozone sensitivity were jointly influenced by its precursors including formaldehyde（HCHO） and nitrogen dioxide（NO2）, while other cities could be categorized into the second group where ozone sensitivities were mainly affected by NO2 column concentrations. Therefore, effective strategies for ozone reduction would be more complex in the first group of cities.

Management and implementation strategies of pre-screening triage in children during coronavirus disease 2019 pandemic in Guangzhou, China.

BACKGROUND: Emerging infectious diseases are a constant threat to the public's health and health care systems around the world. Coronavirus disease 2019 (COVID-2019), which was defined by the World Health Organization as pandemic, has rapidly emerged as a global health threat. Outbreak evolution and prevention of international implications require substantial flexibility of frontline health care facilities in their response. AIM: To explore the effect of the implementation and management strategy of pre-screening triage in children during COVID-19. METHODS: The standardized triage screening procedures included a standardized triage screening questionnaire, setup of pre-screening triage station, multi-point temperature monitoring, extensive screenings, and two-way protection. In order to ensure the implementation of the pre-screening triage, the prevention and control management strategies included training, emergency exercise, and staff protection. Statistical analysis was performed on the data from all the children hospitalized from January 20, 2020 to March 20, 2020 at solstice during the pandemic period. Data were obtained from questionnaires and electronic medical record systems. RESULTS: A total of 17561 children, including 2652 who met the criteria for screening, 192 suspected cases, and two confirmed cases without omission, were screened from January 20, 2020 to March 20, 2020 at solstice during the pandemic period. There was zero transmission of the infection to any medical staff. CONCLUSION: The effective strategies for pre-screening triage have an essential role in the prevention and control of hospital infection.

Association of procalcitonin levels with the progression and prognosis of hospitalized patients with COVID-19.

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions (P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT (P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19.

Differential occupational risks to healthcare workers from SARS-CoV-2: A prospective observational study (preprint)

Background Personal protective equipment (PPE) and social distancing are key measures designed to mitigate the risk of occupational SARS-CoV-2 infection in hospitals. Why healthcare workers nevertheless remain at increased risk is uncertain. Methods We conducted voluntary Covid-19 testing programmes for symptomatic and asymptomatic staff at a large UK teaching hospital using nasopharyngeal PCR testing and immunoassays for IgG antibodies. A positive result by either modality was used as a composite outcome. Risk factors for Covid-19 were investigated using multivariable logistic regression. Results 1083/9809(11.0%) staff had evidence of Covid-19 at some time and provided data on potential risk-factors. Staff with a confirmed household contact were at greatest risk (adjusted odds ratio [aOR] 4.63 [95%CI 3.30-6.50]). Higher rates of Covid-19 were seen in staff working in Covid-19-facing areas (21.2% vs. 8.2% elsewhere) (aOR 2.49 [2.00-3.12]). Controlling for Covid-19-facing status, risks were heterogenous across the hospital, with higher rates in acute medicine (1.50 [1.05-2.15]) and sporadic outbreaks in areas with few or no Covid-19 patients. Covid-19 intensive care unit (ICU) staff were relatively protected (0.46 [0.29-0.72]). Positive results were more likely in Black (1.61 [1.20-2.16]) and Asian (1.58 [1.34-1.86]) staff, independent of role or working location, and in porters and cleaners (1.93 [1.25-2.97]). Contact tracing around asymptomatic staff did not lead to enhanced case identification. 24% of staff/patients remained PCR-positive at [≥]6 weeks post-diagnosis. Conclusions Increased Covid-19 risk was seen in acute medicine, among Black and Asian staff, and porters and cleaners. A bundle of PPE-related interventions protected staff in high-risk ICU areas.

Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study (preprint)

The outbreak of novel coronavirus disease 2019 (COVID-19) has become a pandemic. Drug repurposing may represent a rapid way to fill the urgent need for effective treatment. We evaluated the clinical utility of chloroquine and hydroxychloroquine in treating COVID-19. Forty-eight patients with moderate COVID-19 were randomized to oral treatment with chloroquine (1000 mg QD on Day 1, then 500 mg QD for 9 days; n=18), hydroxychloroquine (200 mg BID for 10 days; n=18), or control treatment (n=12). Adverse events were mild, except for one case of Grade 2 ALT elevation. Adverse events were more commonly observed in the chloroquine group (44.44%) and the hydroxychloroquine group (50.00%) than in the control group (16.67%). The chloroquine group achieved shorter time to clinical recovery (TTCR) than the control group (P=0.019). There was a trend toward reduced TTCR in the hydroxychloroquine group (P=0.049). The time to reach viral RNA negativity was significantly faster in the chloroquine group and the hydroxychloroquine group than in the control group (P=0.006 and P=0.010, respectively). The median numbers of days to reach RNA negativity in the chloroquine, hydroxychloroquine, and control groups was 2.5 (IQR: 2.0-3.8) days, 2.0 (IQR: 2.0-3.5) days, and 7.0 (IQR: 3.0-10.0) days, respectively. The chloroquine and hydroxychloroquine groups also showed trends toward improvement in the duration of hospitalization and findings on lung computerized tomography (CT). This study provides evidence that (hydroxy)chloroquine may be used effectively in treating moderate COVID-19 and supports larger trials.

Epidemiological,clinical and radiological findings in medical staff with COVID-19 in Wuhan, China: a single-centered, retrospective cohort study (preprint)

Backgrounds In December 2019, a pneumonia associated with the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) emerged in Wuhan city, China. As of 20 Feb 2020, a total of 2,055 medical staff infected with SARS-Cov-2 in China had been reported. The predominant cause of the infection and the failure of protection among medical staff remains unclear. We sought to explore the epidemiological, clinical characteristics and prognosis of novel coronavirus-infected medical staff.Methods Medical staff who infected with SARS-Cov-2 and admitted to Union Hospital, Wuhan between 16 Jan, 2020 to 25 Feb, 2020 were included retrospectively. Epidemiological, clinical and radiological data were compared by occupation and analyzed with the Kaplan-Meier and Cox regression methods.Results A total of 101 medical staff (32 males and 69 females; median age: 33 years old) were included in this study and 74% were nurses. None had an exposure to Huanan seafood wholesale market or wildlife. A small proportion of the cohort had contact with specimens (3%) as well as patients infected with SARS-Cov-2 in fever clinics (15%) and isolation wards (3%). 80% of medical staff showed abnormal IL-6 levels and 33% had lymphocytopenia. Chest CT mainly manifested as bilateral (62%), septal/subpleural (77%) and ground­glass opacities (48%). The major differences between doctors and nurses manifested in laboratory indicators. As of the last observed date, no patient was transferred to intensive care unit or died, and 98 (97%) had been discharged. Fever (HR=0.57; 95% CI 0.36-0.90) and IL-6 levels greater than >2.9 pg/ml (HR=0.50; 95% CI 0.30-0.86) on admission were unfavorable factors for discharge.Conclusions Our findings suggested that the infection of medical staff mainly occurred at the early stages of SARS-CoV-2 epidemic in Wuhan, and only a small proportion of infection had an exact mode. Meanwhile, medical staff infected with COVID-19 have relatively milder symptoms and favorable clinical course than other ordinary patients, which may be partly due to their medical expertise, younger age and less underlying diseases. The potential risk factors of presence of fever and IL-6 levels greater than >2.9 pg/ml could help to identify medical staff with poor prognosis at an early stage.

Epidemiological, Clinical Characteristics and Outcome of Medical Staff Infected with COVID-19 in Wuhan, China: A Retrospective Case Series Analysis (preprint)

Backgrounds Since December 2019, a novel coronavirus epidemic has emerged in Wuhan city, China and then rapidly spread to other areas. As of 20 Feb 2020, a total of 2,055 medical staff confirmed with coronavirus disease 2019 (COVID-19) caused by SARS-Cov-2 in China had been reported. We sought to explore the epidemiological, clinical characteristics and prognosis of novel coronavirus-infected medical staff. Methods In this retrospective study, 64 confirmed cases of novel coronavirus-infected medical staff admitted to Union Hospital, Wuhan between 16 Jan, 2020 to 15 Feb, 2020 were included. Two groups concerned were extracted from the subjects based on duration of symptoms: group 1 (<= 10 days) and group 2 (>10 days). Epidemiological and clinical data were analyzed and compared across groups. The Kaplan-Meier plot was used to inspect the change in hospital discharge rate. The Cox regression model was utilized to identify factors associated with hospital discharge. Findings The median age of medical staff included was 35 years old. 64% were female and 67% were nurses. None had an exposure to Huanan seafood wholesale market or wildlife. A small proportion of the cohort had contact with specimens (5%) as well as patients in fever clinics (8%) and isolation wards (5%). Fever (67%) was the most common symptom, followed by cough (47%) and fatigue (34%). The median time interval between symptoms onset and admission was 8.5 days. On admission, 80% of medical staff showed abnormal IL-6 levels and 34% had lymphocytopenia. Chest CT mainly manifested as bilateral (61%), subpleural (80%) and ground-glass (52%) opacities. During the study period, no patients was transferred to intensive care unit or died, and 34 (53%) had been discharged. Higher body mass index (BMI) (HR 0.14; 95% CI 0.03-0.73), fever (HR 0.24; 95% CI 0.09-0.60) and higher levels of IL-6 on admission (HR 0.31; 95% CI 0.11-0.87) were unfavorable factors for discharge. Interpretation In this study, medical staff infected with COVID-19 have relatively milder symptoms and favorable clinical course, which may be partly due to their medical expertise, younger age and less underlying diseases. Smaller BMI, absence of fever symptoms and normal IL-6 levels on admission are favorable for discharge for medical staff. Further studies should be devoted to identifying the exact patterns of SARS-CoV-2 infection among medical staff.