The impact of COVID-19 epidemic on the control of important parasitic diseases.

The spread of COVID-19 has increased the risk of contact transmission between people, and imposes challenges and opportunities for the prevention and control of important parasitic diseases. There may be risks of COVID-19 infection during the implementation of the virus control, including in field investigation and intervention, contacting with fecal samples, or with asymptomatic infected people. Therefore, corresponding prevention and control measures should be taken before and during field investigation, and in sample transportation and detection to prevent the risks effectively. In this paper, the risks and corresponding countermeasures in the above processes are discussed in detail, and the opportunities that COVID-19 brought to the disease control system are also analyzed.Copyright © 2021, National Institute of Parasitic Diseases. All rights reserved.

N-Butanol Extract of Glycyrrhizae Radix et Rhizoma Inhibits Dengue Virus through Targeting Envelope Protein.

BACKGROUND: At present, about half of the world's population is at risk of being infected with dengue virus (DENV). However, there are no specific drugs to prevent or treat DENV infection. Glycyrrhizae Radix et Rhizome, a well-known traditional Chinese medicine, performs multiple pharmacological activities, including exerting antiviral effects. The aim of this study was to investigate the anti-DENV effects of n-butanol extract from Glycyrrhizae Radix et Rhizome (GRE). METHODS: Compounds analysis of GRE was conducted via ultra-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). The antiviral activities of GRE were determined by the CCK-8 assay, plaque assay, qRT-PCR, Western blotting, and the immunofluorescence assay. The DENV-infected suckling mice model was constructed to explore the antiviral effects of GRE in vivo. RESULTS: Four components in GRE were analyzed by UHPLC-MS/MS, including glycyrrhizic acid, glycyrrhetnic acid, liquiritigenin, and isoliquiritigenin. GRE inhibited the attachment process of the virus replication cycle and reduced the expression of the E protein in cell models. In the in vivo study, GRE significantly relieved clinical symptoms and prolong survival duration. GRE also significantly decreased viremia, reduced the viral load in multiple organs, and inhibited the release of pro-inflammatory cytokines in DENV-infected suckling mice. CONCLUSIONS: GRE exhibited significant inhibitory activities in the adsorption stage of the DENV-2 replication cycle by targeting the envelope protein. Thus, GRE might be a promising candidate for the treatment of DENV infection.

The Interaction between Flavonoids and Intestinal Microbes: A Review.

In recent years, research on the interaction between flavonoids and intestinal microbes have prompted a rash of food science, nutriology and biomedicine, complying with future research trends. The gut microbiota plays an essential role in the maintenance of intestinal homeostasis and human health, but once the intestinal flora dysregulation occurs, it may contribute to various diseases. Flavonoids have shown a variety of physiological activities, and are metabolized or biotransformed by gut microbiota, thereby producing new metabolites that promote human health by modulating the composition and structure of intestinal flora. Herein, this review demonstrates the key notion of flavonoids as well as intestinal microbiota and dysbiosis, aiming to provide a comprehensive understanding about how flavonoids regulate the diseases by gut microbiota. Emphasis is placed on the microbiota-flavonoid bidirectional interaction that affects the metabolic fate of flavonoids and their metabolites, thereby influencing their metabolic mechanism, biotransformation, bioavailability and bioactivity. Potentially by focusing on the abundance and diversity of gut microbiota as well as their metabolites such as bile acids, we discuss the influence mechanism of flavonoids on intestinal microbiota by protecting the intestinal barrier function and immune system. Additionally, the microbiota-flavonoid bidirectional interaction plays a crucial role in regulating various diseases. We explain the underlying regulation mechanism of several typical diseases including gastrointestinal diseases, obesity, diabetes and cancer, aiming to provide a theoretical basis and guideline for the promotion of gastrointestinal health as well as the treatment of diseases.

Two-stage hybrid network for segmentation of COVID-19 pneumonia lesions in CT images: a multicenter study.

COVID-19 has been spreading continuously since its outbreak, and the detection of its manifestations in the lung via chest computed tomography (CT) imaging is essential to investigate the diagnosis and prognosis of COVID-19 as an indispensable step. Automatic and accurate segmentation of infected lesions is highly required for fast and accurate diagnosis and further assessment of COVID-19 pneumonia. However, the two-dimensional methods generally neglect the intraslice context, while the three-dimensional methods usually have high GPU memory consumption and calculation cost. To address these limitations, we propose a two-stage hybrid UNet to automatically segment infected regions, which is evaluated on the multicenter data obtained from seven hospitals. Moreover, we train a 3D-ResNet for COVID-19 pneumonia screening. In segmentation tasks, the Dice coefficient reaches 97.23% for lung segmentation and 84.58% for lesion segmentation. In classification tasks, our model can identify COVID-19 pneumonia with an area under the receiver-operating characteristic curve value of 0.92, an accuracy of 92.44%, a sensitivity of 93.94%, and a specificity of 92.45%. In comparison with other state-of-the-art methods, the proposed approach could be implemented as an efficient assisting tool for radiologists in COVID-19 diagnosis from CT images.

The global response: How cities and provinces around the globe tackled Covid-19 outbreaks in 2021.

Background: Tackling the spread of COVID-19 remains a crucial part of ending the pandemic. Its highly contagious nature and constant evolution coupled with a relative lack of immunity make the virus difficult to control. For this, various strategies have been proposed and adopted including limiting contact, social isolation, vaccination, contact tracing, etc. However, given the heterogeneity in the enforcement of these strategies and constant fluctuations in the strictness levels of these strategies, it becomes challenging to assess the true impact of these strategies in controlling the spread of COVID-19. Methods: In the present study, we evaluated various transmission control measures that were imposed in 10 global urban cities and provinces in 2021- Bangkok, Gauteng, Ho Chi Minh City, Jakarta, London, Manila City, New Delhi, New York City, Singapore, and Tokyo. Findings: Based on our analysis, we herein propose the population-level Swiss cheese model for the failures and pitfalls in various strategies that each of these cities and provinces had. Furthermore, whilst all the evaluated cities and provinces took a different personalized approach to managing the pandemic, what remained common was dynamic enforcement and monitoring of breaches of each barrier of protection. The measures taken to reinforce the barriers were adjusted continuously based on the evolving epidemiological situation. Interpretation: How an individual city or province handled the pandemic profoundly affected and determined how the entire country handled the pandemic since the chain of transmission needs to be broken at the very grassroot level to achieve nationwide control. Funding: The present study did not receive any external funding.

Megakaryocytes in pulmonary diseases.

Megakaryocytes (MKs) are typical cellular components in the circulating blood flowing from the heart into the lungs. Physiologically, MKs function as an important regulator of platelet production and immunoregulation. However, dysfunction in MKs is considered a trigger in various diseases. It has been described that the lung is an important site of platelet biogenesis from extramedullary MKs, which may play an essential role in various pulmonary diseases. With detailed studies, there are different degrees of numerical changes of MKs in coronavirus disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary fibrosis (PF), and other pulmonary diseases. Also, MKs inhibit or promote the development of pulmonary diseases through various pathways. Here, we summarize the current knowledge of MKs in pulmonary diseases, highlighting the physiological functions and integrated molecular mechanisms. We aim to shine new light on not only the subsequent study of MKs but also the diagnosis and treatment of pulmonary diseases.

Potential metal-related strategies for prevention and treatment of COVID-19.

Abstract: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed severe threats to human health, public safety, and the global economy. Metal nutrient elements can directly or indirectly take part in human immune responses, and metal-related drugs have served as antiviral drugs and/or enzyme inhibitors for many years, providing potential solutions to the prevention and treatment of COVID-19. Metal-based drugs are currently under a variety of chemical structures and exhibit wide-range bioactivities, demonstrating irreplaceable advantages in pharmacology. This review is an intention to summarize recent progress in the prevention and treatment strategies against COVID-19 from the perspective of metal pharmacology. The current and potential utilization of metal-based drugs is briefly introduced. Specifically, metallohydrogels that have been shown to present superior antiviral activities are stressed in the paper as potential drugs for the treatment of COVID-19.

The Role of Imaging in the Detection and Management of COVID-19: A Review.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading rapidly around the world, resulting in a massive death toll. Lung infection or pneumonia is the common complication of COVID-19, and imaging techniques, especially computed tomography (CT), have played an important role in diagnosis and treatment assessment of the disease. Herein, we review the imaging characteristics and computing models that have been applied for the management of COVID-19. CT, positron emission tomography - CT (PET/CT), lung ultrasound, and magnetic resonance imaging (MRI) have been used for detection, treatment, and follow-up. The quantitative analysis of imaging data using artificial intelligence (AI) is also explored. Our findings indicate that typical imaging characteristics and their changes can play crucial roles in the detection and management of COVID-19. In addition, AI or other quantitative image analysis methods are urgently needed to maximize the value of imaging in the management of COVID-19.

The investigation of energy management and atomic interaction between coronavirus structure in the vicinity of aqueous environment of H2O molecules via molecular dynamics approach.

The coronavirus pandemic is caused by intense acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Identifying the atomic structure of this virus can lead to the treatment of related diseases in medical cases. In the current computational study, the atomic evolution of the coronavirus in an aqueous environment using the Molecular Dynamics (MD) approach is explained. The virus behaviors by reporting the physical attributes such as total energy, temperature, potential energy, interaction energy, volume, entropy, and radius of gyration of the modeled virus are reported. The MD results indicated the atomic stability of the simulated virus significantly reduced after 25.33 ns. Furthermore, the volume of simulated virus changes from 182397 Å3 to 372589 Å3 after t = 30 ns. This result shows the atomic interaction between various atoms in coronavirus structure decreases in the vicinity of H2O molecules. Numerically, the interaction energy between virus and aqueous environment converges to -12387 eV and -251 eV values in the initial and final time steps of the MD study procedure, respectively.

METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection.

It is urgent and important to understand the relationship of the widespread severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) with host immune response and study the underlining molecular mechanism. N6-methylation of adenosine (m6A) in RNA regulates many physiological and disease processes. Here, we investigate m6A modification of the SARS-CoV-2 gene in regulating the host cell innate immune response. Our data show that the SARS-CoV-2 virus has m6A modifications that are enriched in the 3' end of the viral genome. We find that depletion of the host cell m6A methyltransferase METTL3 decreases m6A levels in SARS-CoV-2 and host genes, and m6A reduction in viral RNA increases RIG-I binding and subsequently enhances the downstream innate immune signaling pathway and inflammatory gene expression. METTL3 expression is reduced and inflammatory genes are induced in patients with severe coronavirus disease 2019 (COVID-19). These findings will aid in the understanding of COVID-19 pathogenesis and the design of future studies regulating innate immunity for COVID-19 treatment.

Effects of group psychological intervention combined with pulmonary rehabilitation exercises on anxiety and sleep disorders in patients with mild coronavirus disease 2019 (COVID-19) infections in a Fangcang hospital.

Fangcang hospitals, as tentative hospitals built to treat a huge turnover of patients with mild coronavirus disease 2019 (COVID-19) infections, have played a pivotal role to slow down the pandemic spread in China in 2020. However, anxiety and sleep disorders remain tough to address during the treatments. In this study, group psychological intervention in combination with pulmonary rehabilitation exercises were conducted in the trial group for the patients with mild COVID-19 infections in a Fangcang Hospital to mitigate the patients' anxiety and sleep disorders, while conventional nursing methods were done in the control group, with 70 randomly picked patients in each group. Effects were assessed through questionnaire method using state anxiety questionnaire (SAI) and Pittsburgh sleep quality index scale (PQSI) rating investigation. Results showed that both SAI and PSQI scores of the trial group were significantly lower than those of the control group (P < 0.05). The SAI scores of the trial group and the control group were 38.5 ± 13.2 and 45.8 ± 10.4 points (t = 3.600, P < 0.001), respectively, and the PSQI scores were 5.6 ± 3.0 and 7.1 ± 3.0 points (t = 2.982, P < 0.01), respectively. Our methods have significant advantages over conventional nursing methods to mitigate anxiety and sleep disorders for the patients with mild COVID-19 infections in the Fangcang Hospital.

Incidence and Associated Factors for Neuraxial Anaesthesia-Related Hypotension in COVID-19 Parturients Undergoing Caesarean Delivery: A Multicenter Case-Control Study (preprint)

Background: COVID-19 continues to spread globally and results in additional challenges for perioperative management in parturients. The purpose of this study was to determine the incidence and identify associated factors for neuraxial anaesthesia-related hypotension in COVDI-19 parturients during caesarean delivery.Methods: We performed a multicenter case-control study at 3 medical institutions in Hubei province, China form 1th January to 30th May 2020. All ASA Physical Status II full termed pregnant women who received caesarean delivery under neuraxial anaesthesia were eligible for inclusion. The univariate analysis and binary logistic regression analysis were used to identified the independent predictors of neuraxial anaesthesia-related hypotension.Results: Present study included 102 COVID-19 parturients. The incidence of neuraxial anaesthesia-related hypotension was 58%. Maternal abnormal lymphocyte count (OR = 3.41, p = 0.03), full stomach (OR = 3.22, p = 0.04), baseline heart rate (OR = 1.04, p = 0.03), experience of anaesthetist (OR = 0.86, p = 0.02) and surgeon (OR = 0.76, p = 0.03), and combined spinal-epidural anaesthesia technique (OR = 3.27, p = 0.02) were associated with neuraxial anaesthesia-related hypotension. The area under the receiver operating characteristic curve achieved 0.83 which was significantly higher than 0.5 (p < 0.001). And the sensitivity, specificity and percentage correct were 75%, 79% and 75%, respectively. The Hosmer-Lemeshow test showed a good calibration of the model (H = 2.01, DF = 8, p = 0.98).Conclusions: Maternal abnormal lymphocyte count, full stomach, baseline heart rate, experience of anaesthetist and surgeon, and combined spinal-epidural anaesthesia technique were identified as the independent predictors of neuraxial anaesthesia-related hypotension.

Cholesterol 25-Hydroxylase inhibits SARS-CoV-2 and other coronaviruses by depleting membrane cholesterol.

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 and has spread across the globe. SARS-CoV-2 is a highly infectious virus with no vaccine or antiviral therapy available to control the pandemic; therefore, it is crucial to understand the mechanisms of viral pathogenesis and the host immune responses to SARS-CoV-2. SARS-CoV-2 is a new member of the betacoronavirus genus like other closely related viruses including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Both SARS-CoV and MERS-CoV have caused serious outbreaks and epidemics in the past eighteen years. Here, we report that one of the interferon-stimulated genes (ISGs), cholesterol 25-hydroxylase (CH25H), is induced by SARS-CoV-2 infection in vitro and in COVID-19-infected patients. CH25H converts cholesterol to 25-hydrocholesterol (25HC) and 25HC shows broad anti-coronavirus activity by blocking membrane fusion. Furthermore, 25HC inhibits USA-WA1/2020 SARS-CoV-2 infection in lung epithelial cells and viral entry in human lung organoids. Mechanistically, 25HC inhibits viral membrane fusion by activating the ER-localized acyl-CoA:cholesterol acyltransferase (ACAT) which leads to the depletion of accessible cholesterol from the plasma membrane. Altogether, our results shed light on a potentially broad antiviral mechanism by 25HC through depleting accessible cholesterol on the plasma membrane to suppress virus-cell fusion. Since 25HC is a natural product with no known toxicity at effective concentrations, it provides a potential therapeutic candidate for COVID-19 and emerging viral diseases in the future.

Lymphocytopenia and neutrophilia deteriorate at the lowest oxygenation index timepoint in COVID-19 patient (preprint)

BackgroundCoronavirus disease 2019 (COVID-19) spread throughout the world and caused hundreds of thousands of infected people to death. However, the pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS COV-2) is poorly understood. The objective of this study is to retrospectively explore the pathogenesis of COVID-19 from clinical laboratory findings, taking disease progression into account.MethodsA single-centered, retrospective study was carried out, which included moderate (n=76) and severe COVID-19 cases (n=22). The difference of laboratory findings from blood routine examination and hepatorenal function test were retrospectively evaluated between the state of moderate and severe. The disease progression was indicated by oxygenation index.ResultsAge is a risk factor for disease progression from moderate to severe. Lymphocytopenia, neutrophilia, liver and kidney function decreasement occurred in severe patients on admission, compared with moderate patients. Lymphocytopenia and neutrophilia deteriorated at the lowest oxygenation index timepoint in the severe patients. And the oxygenation index was associated with ratio of lymphocyte and neutrophil in COVID-19 patients.ConclusionsLymphocytopenia and neutrophilia, which deteriorate in the progression of severe patients, are the main pathogenesis of COVID-19. More measures need to be taken to control lymphocytopenia and neutrophilia in severe COVID-19. Oxygenation index presented potentiality as predictor on the progression of COVID-19.  

Treatment of Covid-19 Patients With High Dose of Ulinastatin (preprint)

Background No specific therapeutic agents or vaccines are available for the treatment of Coronavirus disease 2019 (Covid-19) yet. In this study, we aimed to assess the efficacy of high dose ulinastatin for patients with Covid-19.Methods Twelve patients hospitalized with confirmed SARS-CoV-2 infection were treated with high dose of ulinastatin beyond standard care. The changes of clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. Results A total of 10 patients with severe Covid-19 and 2 patients with moderate Covid-19 received ulinastatin treatment. The average age of the patients was 68.0 ± 11.9 years, ranging from 48 to 87 years. Nine of 12 patients (75.0%) had one or more comorbidities. The most common symptoms on admission were fever (8/12, 66.7%), cough (5/12, 41.7%) and dyspnea (5/12, 41.7%). The percentage of lymphocytes was decreased in 41.7% of patients (5/12), and 58.3% of patients (7/12) had elevated hypersensitive C-reactive protein (CRP) levels (mean, 49.70 ± 77.70 mg/L). The white blood cell levels and the percentage of lymphocytes returned to normal in all of the patients, and CRP decreased significantly and returned to normal in 83.3% of patients (10/12; mean, 6.87 ± 6.63 mg/L) on the seventh day after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not need further oxygen therapy seven days after ulinastatin treatment. No patients required intensive care unit admission or mechanical ventilation. All patients revealed different degrees of absorption of pulmonary lesions after treatment. No obvious adverse events were observed.Conclusions Our preliminary data revealed that high dose of ulinastatin treatment was safe and showed a potential beneficial effect for patients with Covid-19.

[Feasibility analysis on acupuncture therapy for the treatment of Corona Virus Disease 2019 and the exploration on the application scheme].

The situation of Corona Virus Disease 2019 (COVID-19) is still severe at present. In order to better fight against the epidemic and give full play to the advantages of traditional Chinese medicine, we explored the feasibility of acupuncture therapy in the intervention of COVID-19 through analyzing the relevant literature in both ancient and modern time. Additionally, we analyzed the intervention scheme of acupuncture for COVID-19 developed by China Association of Acupuncture and Moxibustion and supplemented the protocol of the intervention with auricular acupuncture. It was proposed that the advantages of acupuncture and moxibustion should be fully displayed while Chinese herbal medications have been applied in the treatment of COVID-19. During treatment, acupuncture physicians should be rationally allocated to a certain proportion so as to adequately utilize comprehensive therapeutic approaches and guarantee people's safety to the greatest extent. Eventually, the clinical therapeutic effect may be improved, the national resources be economized on and the COVID-19 epidemic be conquered early.

Anaesthetic managment and clinical outcomes of parturients with COVID-19: a multicentre, retrospective, propensity score matched cohort study (preprint)

Objective:To analyse the clinical features of COVID-19 parturients, and to compare anaesthetic regimen and clinical outcomes in parturients with or without COVID-19 undergoing cesarean delivery.Methods: Data were extracted from the electronic medical record of 3 medical institutions in Hubei Province, China, from June 1, 2019 to March 20, 2020 according to inclusion and exclusion criteria. After propensity score matching with demographics, the clinical and laboratory characteristics of parturients with or without COVID-19 were analysed. The anaesthetic regimen and clinical outcomes of themselves and their infants were compared in these two groups of parturients. Results: A total of 1,588 patients without SARS-CoV-2 infection undergoing cesarean delivery were retrospectively included. After achieving a balanced cohort through propensity score matching, 89 patients (COVID-19 group), who were diagnosed with COVID-19 by SARS-CoV-2 nucleic acid test and CT scan matched with 173 patients without COVID-19 (Control group). The SARS-CoV-2 infected parturients in the early stages of COVID-19 outbreak was much more than during the later stage. The main clinical characteristics of parturients with COVID-19 were fever (34.8%), cough (33.7%), an increased plasma CRP (52.8%) and a decreased lymphocyte counting (33.7%). A high rate of emergency and a high incidence of anaesthesia-related complications, such as pharyngalgia, multiple puncture, intraoperative hypotension, nausea, vomiting, vertigo and chills in the COVID-19 parturients. In addition, the parturients with COVID-19 had a long duration of operation and hospital stay, and an increased intraoperative oxytocin utilization and postoperative oxygen therapy. The newborns from the SARS-CoV-2 infected mothers, who received general anaesthesia, had a high risk of Apgar score [≤]8 at 1 and 5 minutes after delivery and a higher rate of neonatal intensive care unit (NICU) admission. Conclusions: Anaesthesia-related complications occur more frequently in the COVID-19 parturients and their newborns have a high risk of distress.