Impact of COVID-19 pandemic on the psychosocial well-being of children with neuromuscular disorders (preprint)

To examine the impact of COVID-19 on the psychosocial wellbeing in children with neuromuscular disorders (NMD), the parents of 41 children with NMD aged 3-12 years completed a survey during COVID-19 pandemic. The findings were compared to those of the parents of 164 matched typically-developed (TD) children. Health-related quality of life and lifestyle habits of the NMD group were compared with the TD group using independent two-sample t-test. Children with NMD with uninterrupted disease-modifying treatments showed higher PedsQL total scores during the pandemic compared to the pre-pandemic state (p=0.012). PedsQL total score in the NMD group was significantly lower than the TD group (p<0.001). Those with disrupted rehabilitation training (73.8% of NMD group) had significant lower PedsQL scores compared to those with continuous training (p = 0.012). Parental guidance on the usage of electronic devices was significantly associated with the total score of PedsQL, particularly in the NMD group (p=0.007). In conclusion, children with NMD have had a poorer quality of life than TD children during the COVID-19 pandemic. Our study highlights the importance of parental guidance on electronic device usage, the continuation of drug treatment, and rehabilitation training for the psychosocial wellbeing of children with NMD during the pandemic.

To Explore the Network Pharmacology and Molecular Docking Mechanism of Chaihu Shugan Powder with the “Same Treatment for Different Diseases” for Insomnia and Depression Based on the COVID-19 Pandemic (preprint)

Background: The classic prescription Chaihu Shugan Powder (CHSGP) has been widely used in clinical Chinese medicine treatment and has clear clinical effects in the treatment of emotional diseases. Based on the increasing incidence of emotional diseases such as insomnia and depression in the population during the COVID-19 pandemic, we will explore the mechanism of CHSGP in the treatment of insomnia and depression with “Same Treatment for Different Diseases”. Methods: Using a bioinformatics and network pharmacology platform, protein database and STRING database, we collected CHSGP chemical composition and related target data and constructed a "component-target" action network through Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis. Molecular docking technology was used to verify key active ingredients and core targets. Results: A total of 119 active compounds of CHSGP were screened, such as quercetin, kaempferol, and β-sitosterol, and 113 common related targets overlapped with insomnia and depression. GO enrichment and KEGG pathway analysis mainly involved immune, inflammation, cell proliferation, apoptosis, endocrine and other related targets and signaling pathways. Molecular docking showed that small molecular compounds (kaempferol, luteolin, quercetin, 7-methoxy-2-methyl isoflavone and beta-sitosterol) had good binding effects with five target proteins (AKT1, IL1B, IL-6, FOS, GSK3B) to play a role in regulating immunity, the inflammatory response, cell proliferation, apoptosis, and endocrine signaling. Conclusions: Under the context of the COVID-19 pandemic, it revealed the complex mechanism of multicomponent, multitarget, and multipathway of the classic CHSGP for insomnia and depression, laying a theoretical foundation for its clinical application of its "same treatment for different diseases".

Interferon-induced transmembrane protein 3 (IFITM3) limits lethality of SARS-CoV-2 in mice (preprint)

Interferon-induced transmembrane protein 3 (IFITM3) is a host antiviral protein that alters cell membranes to block fusion of viruses. Published reports have identified conflicting pro- and anti-viral effects of IFITM3 on SARS-CoV-2 in cultured cells, and its impact on viral pathogenesis in vivo remains unclear. Here, we show that IFITM3 knockout (KO) mice infected with mouse-adapted SARS-CoV-2 experienced extreme weight loss and lethality, while wild type (WT) mice lost minimal weight and recovered. KO mice had higher lung viral titers and increases in lung inflammatory cytokine levels, CD45-positive immune cell infiltration, and histopathology, compared to WT mice. Mechanistically, we observed disseminated viral antigen staining throughout the lung tissue and pulmonary vasculature in KO mice, while staining was observed in confined regions in WT lungs. Global transcriptomic analysis of infected lungs identified upregulation of gene signatures associated with interferons, inflammation, and angiogenesis in KO versus WT animals, highlighting changes in lung gene expression programs that precede severe lung pathology and fatality. Corroborating the protective effect of IFITM3 in vivo, K18-hACE2/IFITM3 KO mice infected with non-adapted SARS-CoV-2 showed enhanced, rapid weight loss and early death compared to control mice. Increased heart infection was observed in both mouse models in the absence of IFITM3, indicating that IFITM3 constrains extrapulmonary dissemination of SARS-CoV-2. Our results establish IFITM3 KO mice as a new animal model for studying severe SARS-CoV-2 infection of the lung and cardiovascular system, and overall demonstrate that IFITM3 is protective in SARS-CoV-2 infections of mice.

Comparative evaluation of the transmissibility of SARS-CoV-2 variants of concern (preprint)

Since the start of the SARS-CoV-2 pandemic in late 2019, several variants of concern (VOC) have been reported, such as B.1.1.7, B.1.351, P.1, and B.1.617.2. The exact reproduction number Rt for these VOCs is important to determine appropriate control measures. Here, we estimated the transmissibility for VOCs and lineages of SAR-CoV-2 based on genomic data and Bayesian inference under an epidemiological model to infer the reproduction number (Rt). We analyzed data for multiple VOCs from the same time period and countries, in order to compare their transmissibility while controlling for geographical and temporal factors. The lineage B had a significantly higher transmissibility than lineage A, and contributed to the global pandemic to a large extent. In addition, all VOCs had increased transmissibility when compared with other lineages in each country, indicating they are harder to control and present a high risk to public health. All countries should formulate specific prevention and control policies for these VOCs when they are detected to curve their potential for large-scale spread.

The molecular basis for SARS-CoV-2 recognized by dog ACE2 (preprint)

SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin converting enzyme 2 (dACE2) can bind to SARS-CoV-2 spike (S) protein receptor binding region (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. we solved the crystal structure of RBD in complex with dACE2 and found that the total numbers of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that to hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2, and need intense monitoring and controlling.

Stigma and Misconceptions in the Time of the Covid-19 Pandemic: A Field Experiment in India (preprint)

A hidden cost of the COVID-19 pandemic is the stigma associated with the disease for those infected and groups that are considered as more likely to be infected. This paper examines whether the provision of accurate and focused information about COVID-19 from a reliable source can reduce stigmatization. We carry out a randomized field experiment in the state of Uttar Pradesh, India, in which we provide an information brief about COVID-19 by phone to a random subsample of participants to address stigma and misconceptions. We find that the information brief decreases stigmatization of COVID-19 patients and certain groups such as religious minorities, lower-caste groups, and frontline workers (healthcare, police), and reduces the belief that infection cases are more prevalent among certain marginalized social and economic groups (Muslims, low caste, rural-poor population). We provide suggestive evidence that improved knowledge about the prevention and transmission of COVID-19 and reduced stress about the disease are important channels for these effects.

Short-Term Lifestyle Alteration and All-Cause Mortality: Lessons from COVID-19 Prevention in a Low-Transmission Region (preprint)

Background: The COVID-19 mortality is very low in the regions with a low transmission rate and sufficient medical resources. However, strict prevention measures greatly altered people’s social activities, diet, and hygienic habits, which had potential impact on non-COVID-19 deaths. Therefore, this study is to evaluate the impact of short-term lifestyle change on non-COVID deaths in the region with a low COVID-19 transmission rate.Methods: We performed a retropective observational study with statiscal analysis via Student’s t-test (significance defined as P-value < 0.05). The number of registered deaths among 8.8 million permanent residents with specific causes from January 2018 to June 2020 were sourced from Xuzhou Center for Disease Control and Prevention. Death rates were calculated and compared by weeks, months, and years with a focus on the period of COVID-19 pandemic from Jan 24 to March 27, 2020 in Xuzhou, Jiangsu Province, China.Findings: Within the COVID-19 timeframe, all-cause mortality (138.03/105 vs. 158.28/105 vs. 152.57/105, P < 0.001), respiratory disorders (13.99/105 vs. 24.48/105 vs. 21.22/105, P < 0.001), cerebrovascular diseases (36.35/105 vs. 38.69/105 vs. 38.61/105, P < 0.05), and cardiovascular diseases (35.70/105 vs. 42.06/105 vs. 39.55/105, P < 0.001) are consistently lower than those in the same period in 2018 and 2019. The traffic death dropped significantly, while mortalities of mental health disorders and out-of-hospital sudden death significantly increased during the pandemic time.Interpretation: Our study suggests the short-term lifestyle alteration can have significant impact on all-cause mortality. This could provide evidences for adjusting future healthcare policies to reduce specific-cause mortalities such as respiratory, cardiovascular and cerebrovascular diseases.Trial Registration: This study was registered at the ClinicalTrials.gov (NCT 04550312). Funding: Xuzhou Talent Fellowship Program 2019.Conflict of Interest: We declare no competing interests.Ethical Approval: The medical research ethics committee of the affiliated hospital of Xuzhou Medical University, Xuzhou, approved the study (9th, September 2020, No. XYFY2020-KL142-01).

Impact of Lifestyle Alteration on Non-COVID Deaths by Prevention Measures in the Region with a Low COVID-19 Transmission Rate (preprint)

Background: The increase of all-cause mortality in the areas with high COVID-19 transmission rate due to COVID-19 deaths and the collateral damage to other healthcare problems is well-known. However, the COVID-19 mortality is low in the regions with a low transmission rate and sufficient medical resources. In such regions, strict prevention measures altered people’s lifestyle and hygienic habits and had an impact on non-COVID-19 deaths. Yet, this aspect needs to be elucidated further.Methods: The number of registered deaths among 8.8 million permanent residents with specific causes from January 2018 to June 2020 were estimated. Death rates were calculated and compared by weeks, months, seasons and years with a focus on the period of the COVID-19 pandemic from January 24 to March 27, 2020. The numerical values of all-cause death and the death rates of non-COVID diseases were compared in various time points.Findings: During the pandemic in Xuzhou region, a total of 79 COVID-19 infected patients were diagnosed and treated. Meanwhile, stringent public health measures were taken to contain the virus transmission. Surprisingly, mortalities of all-cause casualty, respiratory disorders, cerebrovascular disease, and cardiovascular disease are consistently lower than those in the same periods in 2018 and 2019. Moreover, the first two weeks in the lunar new year presented the highest death rates from 2018–2020 and lowest in 2020 due to COVID-19 control. The traffic death dropped significantly, while mortality of mental health disorders and out-of-hospital sudden death significantly increased during the pandemic time.Interpretation: Control strategies in the region of low SARS-CoV-2 transmission rate during the COVID-19 outbreak alter the lifestyles of people and further exert an impact on non-COVID deaths, which could have a practical value in guiding clinical work and future management of chronic diseases.Funding Statement: Xuzhou Talent Fellowship Program 2019Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study was approved by the Institutional Review Board at the affiliated hospital of Xuzhou Medical University.

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.

Using RIGHT (Reporting Items for Practice Guidelines in Healthcare) to evaluate the reporting quality of WHO guidelines

BACKGROUND: Without adequate reporting of research, valuable time and resources are wasted. In the same vein, adequate reporting of practice guidelines to optimise patient care is equally important. Our study examines the quality of reporting of published WHO guidelines, over time, using the RIGHT (Reporting Items for Practice Guidelines in HealThcare) reporting checklist. METHODS: We examined English-language guidelines approved by the WHO Guidelines Review Committee from inception of the committee in 2007 until 31 December 2017. Pairs of independent, trained reviewers assessed the reporting quality of these guidelines. Descriptive data were summarised with frequencies and percentages. RESULTS: We included 182 eligible guidelines. Overall, 25 out of the 34 RIGHT items were reported in 75% or more of the WHO guidelines. The reporting rates improved over time. Further, 90% of the guidelines reported document type in the title. The identification of evidence, the rationale for recommendations and the review process were reported in more than 80% of guidelines. The certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was assessed in 81% of the guidelines assessed. While 82% of guidelines reported funding sources, only 25% mentioned the role of funders. CONCLUSIONS: WHO guidelines provide adequate reporting of many of the RIGHT items and reporting has improved over time. WHO guidelines compare favourably to guidelines produced by other organisations. However, reporting can be further improved in a number of areas.

Development and Validation of a Diagnostic Nomogram to Predict COVID-19 Pneumonia (preprint)

Background The COVID-19 virus is an emerging virus associated with severe respiratory illness first detected in December, 2019, and rapidly spread worldwide. The aim of this study was to establish an effective diagnostic nomogram for suspected COVID-19 pneumonia patients. Methods We used the LASSO aggression and multivariable logistic regression methods to explore the predictive factors associated with COVID-19 pneumonia, and established the diagnostic nomogram for COVID-19 pneumonia using multivariable regression. This diagnostic nomogram was assessed by the internal and external validation data set. Further, we plotted decision curves and clinical impact curve to evaluate the clinical usefulness of this diagnostic nomogram. Results The predictive factors including the epidemiological history, wedge-shaped or fan-shaped lesion parallel to or near the pleura, bilateral lower lobes, ground glass opacities, crazy paving pattern and white blood cell (WBC) count were contained in the nomogram. In the primary cohort, the C-statistic for predicting the probability of the COVID-19 pneumonia was 0.967, even higher than the C-statistic (0.961) in initial viral nucleic acid nomogram which was established using the univariable regression. The C-statistic was 0.848 in external validation cohort. Good calibration curves were observed for the prediction probability in the internal validation and external validation cohort. The nomogram both performed well in terms of discrimination and calibration. Moreover, decision curve and clinical impact curve were also beneficial for COVID-19 pneumonia patients. Conclusion Our nomogram can be used to predict COVID-19 pneumonia accurately and favourably.

Development and Validation of a Diagnostic Nomogram to Predict COVID-19 Pneumonia (preprint)

Background: The COVID-19 virus is an emerging virus rapidly spread worldwide This study aimed to establish an effective diagnostic nomogram for suspected COVID-19 pneumonia patients. METHODS: We used the LASSO aggression and multivariable logistic regression methods to explore the predictive factors associated with COVID-19 pneumonia, and established the diagnostic nomogram for COVID-19 pneumonia using multivariable regression. This diagnostic nomogram was assessed by the internal and external validation data set. Further, we plotted decision curves and clinical impact curve to evaluate the clinical usefulness of this diagnostic nomogram. RESULTS: The predictive factors including the epidemiological history, wedge-shaped or fan-shaped lesion parallel to or near the pleura, bilateral lower lobes, ground glass opacities, crazy paving pattern and white blood cell (WBC) count were contained in the nomogram. In the primary cohort, the C-statistic for predicting the probability of the COVID-19 pneumonia was 0.967, even higher than the C-statistic (0.961) in initial viral nucleic acid nomogram which was established using the univariable regression. The C-statistic was 0.848 in external validation cohort. Good calibration curves were observed for the prediction probability in the internal validation and external validation cohort. The nomogram both performed well in terms of discrimination and calibration. Moreover, decision curve and clinical impact curve were also beneficial for COVID-19 pneumonia patients. CONCLUSION: Our nomogram can be used to predict COVID-19 pneumonia accurately and favourably.

Descriptive study of the first 63 cases of the ongoing SARS-CoV-2 outbreak at the transportation hub city Xuzhou in China (preprint)

A novel coronavirus (SARS-CoV-2) outbreak from Wuhan, China has, as of February 13, 2020, infected nearly 60,000 people in China with the death toll passing 1300. The virus is also spreading worldwide rapidly, with 490 confirmed cases in 24 countries and 1 death at current stage. Numerous studies have recently been published in terms of genome structure, transmission, infection mechanism, and drug development of the SARS-CoV-2 virus. In this study, we performed a descriptive study by focusing on the first 63 confirmed COVID-19 cases in Xuzhou, a major city and a transportation hub with 10.44 million population (National Bureau of Statistics of China, 2019) on the east coast of China. Among the 63 patients with confirmed COVID-19, the median age is 45-year-old and 49.21% are male. 23 cases (36.51%) are imported. 23 cases (36.51%) were confirmed between from January 26 to 31 while 40 cases (63.49%) from February 1 to 10. The mean period from isolation to confirmation is 4.95 days. Among the ten administrative divisions of Xuzhou city, Suining county (n=17) and Pizhou City (n=15) have the most cases while Tongshan district has none. A representative familial cluster was analysed in detail in order to get a better understanding of the transmission routes of the virus. Clinical symptoms associated with COVID-19 in 41 confirmed cases were analysed, which could provide a meaningful understanding during the initial screening of the disease. In sum, this study provides an epidemiological overview of the SARS-CoV-2 outbreak in Xuzhou, the economic hub of Huaihai Economic Zone (HEZ) and an important transportation center in China. Considering the ongoing situation of this newly emerged infection both domestically and internationally, more efforts should be required to reduce the transmission of the virus so as to avoid further casualties, economic losses, and global pandemic.Authors Liang Wang, Jiawei Yan, and Zhanzhong Liu contributed equally to this study.

Strategies for the development of drugs targeting novel coronavirus 2019-nCoV / 药学学报

@# There is no specific drug that has been approved for 2019-nCoV. There are a number of factors that pose major challenges in their development. Approaches to the development of anti-2019-nCoV include screening existing broad-spectrum antiviral drugs, repositioning of readily available clinical compounds, and <italic>de novo</italic> development of novel and specific agents for 2019-nCoV. Candidate compounds can be developed either to inhibit virus-based targets, such as RNA proteases, polymerase, spike glycoproteins, and viral envelop and membrane proteins, or to inhibit host-based targets, such as receptors and proteases that are utilized by virus for viral entry and endocytosis. Recently, the RNA polymerase remdesivir had demonstrated clinical efficacy in one patient with severe novel coronavirus pneumonia (NCP). The broad-spectrum viral protease inhibitor Kaletra^® is also recommended in the current NCP clinical practice. Both drugs had lately been proceeded into multiple controlled phase III clinical trials to test their safety and efficacy in NCP. Combinational therapies consisting of multiple drugs provide other viable options against 2019-nCoV, based on scientific and clinical rationales. Using bioinformatics and database analysis, we have identified 75 clinically compounds, including 20 marketed compounds, that are efficacious in inhibiting key targets in virus- and host-based approaches, which may facilitate the development of new therapeutic options for 2019-nCoV.

Practice and thinking of the informationized cabin hospitals during the novel coronavirus pneumonia period / 中华医院管理杂志

Novel coronavirus pneumonia, which has emerged in Wuhan since the end of 2019, has posed a huge challenge for medical institutions in the city. Rapid completion of a number of cabin hospitals plays a vital role in preventing further spreading of the epidemic, by means of collecting and treating mild patients of the disease. This paper presents the key process of Tongji Hospital in its rapid informatization since it took over a cabin hospital. Based on the network architecture of the Tongji cloud platform, the shared service center is used to share data and integrate services between the cabin hospital and Tongji hospital. This practice can prevent cross-infection and improve service efficiency as well, hence offering a reference for future information infrastructure development of cabin hospitals.

AGTR2, One Possible Novel Key Gene for the Entry of 2019-nCoV into Human Cells (preprint)

Recently, it was confirmed that ACE2 is the receptor of 2019-nCoV, the pathogen causing the recent outbreak of severe pneumonia in China. It is confused that ACE2 is widely expressed across a variety of organs and is expressed moderately but not highly in lung, which, however, is the major infected organ. It remains unclear why it is the lung but not other tissues among which ACE2 highly expressed is mainly infected. We hypothesized that there could be some other genes playing key roles in the entry of 2019-nCoV into human cells. Here we found that AGTR2 (angiotensin II receptor type 2), a G-protein coupled receptor, has interaction with ACE2 and is highly expressed in lung with a high tissue specificity. More importantly, simulation of 3D structure based protein-protein interaction reveals that AGTR2 shows a higher binding affinity with the Spike protein of 2019-nCov than ACE2 (energy score: -15.7 vs. -6.9 [kcal/mol]). Given these observations, we suggest that AGTR2 could be a putative novel gene for the the entry of 2019-nCoV into human cells but need further confirmation by biological experiments. Finally, a number of compounds, biologics and traditional Chinese medicine that could decrease the expression level of AGTR2 were predicted.

Possible Inhibitors of ACE2, the Receptor of 2019-nCoV (preprint)

Most recently, an outbreak of severe pneumonia caused by the infection of 2019-nCoV, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Many important aspects about 2019-nCoV remain largely unknown, among which, the limitation of antiviral therapies represents one of the most critical problems. More recently, it was confirmed that human ACE2 is the receptor for the entry of 2019-nCoV into lower respiratory tract epithelial cells. Give this observation, it is thus expected that the virus could be inhibited if we decrease the expression of ACE2. Here by screening two databases, Connectivity Map (CMap) and our JeaMoon Map (JMap), we identified a number of candidate agents that decrease ACE2 expression. CMap analysis identified 5 compounds, among which, Azathioprine is a possible therapeutic strategy for anti-2019-nCoV. Moreover, JMap analysis revealed a number of comounds, biologics, and traditional Chinese medicine, among which, Andrographis, Urtica, Sambucus, Astragalus, valproic acid, butyrate, and epoxomicin represent the most significant and possible strategies for anti-2019-nCoV therapies. This study provides a number of clues and possible therapeutic strategies for 2019-nCoV prevention and treatment.