Synergistic effect of elevated glucose levels with SARS-CoV-2 spike protein induced NOX-dependent ROS production in endothelial cells.

BACKGROUND: Diabetic patients infected with coronavirus disease 2019 (COVID-19) often have a higher probability of organ failure and mortality. The potential cellular mechanisms through which blood glucose exacerbates tissue damage due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still unclear. METHODS AND RESULTS: We cultured endothelial cells within differing glucose mediums with an increasing concentration gradient of SARS-CoV-2 Spike protein (S protein). S protein can cause the reduction of ACE2 and TMPRSS2, and activation of NOX2 and NOX4. A high glucose medium was shown to aggravate the decrease of ACE2 and activation of NOX2 and NOX4 in cultured cells, but had no effect on TMPRSS2. S protein mediated activation of the ACE2-NOX axis induced oxidative stress and apoptosis within endothelial cells, leading to cellular dysfunction via the reduction of NO and tight junction proteins which may collectively be exacerbated by elevated glucose. In addition, the glucose variability model demonstrated activation of the ACE2-NOX axis in a similar manner observed in the high glucose model in vitro. CONCLUSIONS: Our present study provides evidence for a mechanism through which hyperglycemia aggravates endothelial cell injury resulting from S protein mediated activation of the ACE2-NOX axis. Our research thus highlights the importance of strict monitoring and control of blood glucose levels within the context of COVID-19 treatment to potentially improve clinical outcomes.

The Applications of Electrochemical Immunosensors in the Detection of Disease Biomarkers: A Review.

Disease-related biomarkers may serve as indicators of human disease. The clinical diagnosis of diseases may largely benefit from timely and accurate detection of biomarkers, which has been the subject of extensive investigations. Due to the specificity of antibody and antigen recognition, electrochemical immunosensors can accurately detect multiple disease biomarkers, including proteins, antigens, and enzymes. This review deals with the fundamentals and types of electrochemical immunosensors. The electrochemical immunosensors are developed using three different catalysts: redox couples, typical biological enzymes, and nanomimetic enzymes. This review also focuses on the applications of those immunosensors in the detection of cancer, Alzheimer's disease, novel coronavirus pneumonia and other diseases. Finally, the future trends in electrochemical immunosensors are addressed in terms of achieving lower detection limits, improving electrode modification capabilities and developing composite functional materials.

A smartphone-based zero-effort method for mitigating epidemic propagation.

A large number of epidemics, including COVID-19 and SARS, quickly swept the world and claimed the precious lives of large numbers of people. Due to the concealment and rapid spread of the virus, it is difficult to track down individuals with mild or asymptomatic symptoms with limited human resources. Building a low-cost and real-time epidemic early warning system to identify individuals who have been in contact with infected individuals and determine whether they need to be quarantined is an effective means to mitigate the spread of the epidemic. In this paper, we propose a smartphone-based zero-effort epidemic warning method for mitigating epidemic propagation. Firstly, we recognize epidemic-related voice activity relevant to epidemics spread by hierarchical attention mechanism and temporal convolutional network. Subsequently, we estimate the social distance between users through sensors built-in smartphone. Furthermore, we combine Wi-Fi network logs and social distance to comprehensively judge whether there is spatiotemporal contact between users and determine the duration of contact. Finally, we estimate infection risk based on epidemic-related vocal activity, social distance, and contact time. We conduct a large number of well-designed experiments in typical scenarios to fully verify the proposed method. The proposed method does not rely on any additional infrastructure and historical training data, which is conducive to integration with epidemic prevention and control systems and large-scale applications.

COVID-19 chest X-ray image classification in the presence of noisy labels.

The Corona Virus Disease 2019 (COVID-19) has been declared a worldwide pandemic, and a key method for diagnosing COVID-19 is chest X-ray imaging. The application of convolutional neural network with medical imaging helps to diagnose the disease accurately, where the label quality plays an important role in the classification problem of COVID-19 chest X-rays. However, most of the existing classification methods ignore the problem that the labels are hardly completely true and effective, and noisy labels lead to a significant degradation in the performance of image classification frameworks. In addition, due to the wide distribution of lesions and the large number of local features of COVID-19 chest X-ray images, existing label recovery algorithms have to face the bottleneck problem of the difficult reuse of noisy samples. Therefore, this paper introduces a general classification framework for COVID-19 chest X-ray images with noisy labels and proposes a noisy label recovery algorithm based on subset label iterative propagation and replacement (SLIPR). Specifically, the proposed algorithm first obtains random subsets of the samples multiple times. Then, it integrates several techniques such as principal component analysis, low-rank representation, neighborhood graph regularization, and k-nearest neighbor for feature extraction and image classification. Finally, multi-level weight distribution and replacement are performed on the labels to cleanse the noise. In addition, for the label-recovered dataset, high confidence samples are further selected as the training set to improve the stability and accuracy of the classification framework without affecting its inherent performance. In this paper, three typical datasets are chosen to conduct extensive experiments and comparisons of existing algorithms under different metrics. Experimental results on three publicly available COVID-19 chest X-ray image datasets show that the proposed algorithm can effectively recover noisy labels and improve the accuracy of the image classification framework by 18.9% on the Tawsifur dataset, 19.92% on the Skytells dataset, and 16.72% on the CXRs dataset. Compared to the state-of-the-art algorithms, the gain of classification accuracy of SLIPR on the three datasets can reach 8.67%-19.38%, and the proposed algorithm also has certain scalability while ensuring data integrity.

COVID-19 vaccination status and associated factors among lactating women during the COVID-19 outbreak: a cross-sectional study in southern China.

OBJECTIVES: Different countries and institutions around the world have debated whether lactating women should receive the COVID-19 vaccine during the COVID-19 pandemic. In China, lactating is not a contraindication to vaccination, but many women are still hesitant to get vaccinated. The purpose of this study was to investigate the current status of COVID-19 vaccination among lactating women and the related factors affecting vaccination. METHODS: An online cross-sectional survey involving 506 lactating women was conducted in southern China. We explored the related factors affecting COVID-19 vaccination of lactating women from three aspects: general information, knowledge-attitude-behaviour towards COVID-19 and its vaccine, and postpartum psychological state. RESULTS: A total of 432 lactating women completed the questionnaire, 198 of whom had received the COVID-19 vaccine. On the knowledge-attitude-behaviour questionnaire on COVID-19 and its vaccines, the vaccinated group scored higher than the unvaccinated group on both the three subdimensions of the questionnaire and the total score (p<0.01). The results of binary logistics regression analysis showed that mixed feeding (OR=2.68, 95% CI: 1.82 to 3.96), longer breastfeeding duration (OR=1.31, 95% CI: 1.16 to 1.49), better physical condition (OR=5.28, 95% CI: 1.82 to 15.32), higher attitude score of COVID-19 and its vaccine (OR=1.18, 95% CI: 1.10 to 1.27), and having a travel history in medium high-risk areas (OR=3.49, 95% CI: 1.46 to 8.37) were significantly associated with COVID-19 vaccination in lactating women. Having a master's degree or above (OR=0.03, 95% CI: 0.01 to 0.30), and having higher anxiety score (OR=0.66, 95% CI: 0.54 to 0.81) and depression score (OR=0.84, 95% CI: 0.75 to 0.93) were inversely associated with COVID-19 vaccination in lactating women. CONCLUSION: 45.8% of lactating women were vaccinated against COVID-19. Education level, feeding methods, duration of breast feeding, travel history in medium high-risk areas, physical condition, attitude score of COVID-19 and its vaccine, anxiety symptom and depressive symptom score were associated with vaccination of lactating women. More interventions based on these factors were needed to reduce concerns for lactating women and increase their vaccination rates.

Successful Virtual Delivery of a Group Childhood Healthy Weight Program.

Because of the COVID-19 pandemic, the Get Up & Go program, an established effective 10-week healthy weight program for children ages 6-14 years provided free to families, has offered the option of a synchronous virtual delivery. Pre- and postassessments include a parental questionnaire about child's health behaviors, and weight and height measurements of children. Over 3 cycles, 116 and 107 families registered for virtual and in-person delivery, respectively, with 70 (60.3%) and 84 (78.5%) attending ≥1 session (p = 0.003). More families in virtual delivery spoke Spanish (41.4% vs. 22.6%, p = 0.01), but children did not differ in age, gender, and severe obesity status, and baseline behavior scores and graduation rates were similar. Improvement from baseline in BMIp95 was -3.71 [standard deviation (SD) 5.26] for virtual delivery and -1.95 (3.69) (p = 0.06) for in-person. Behavior questionnaire improvement [+15.9 (12.9) vs. +14.2 (12.0), p = 0.51] did not differ. The virtual implementation demonstrated good effect and may be useful in nonpandemic environments.

Corticosteroids Utilization in the Management of Critically Ill Coronavirus Disease-2019 Pneumonia

Background: There are controversies regarding corticosteroids using in coronavirus disease-2019 (COVID-19) pneumonia in the current pandemic. Objectives: This study investigates the efficacy and safety profiles of corticosteroids therapy in COVID-19 patients. Methods: Retrospective, multicenter study case series of consecutive patients with confirmed COVID-19 infection at the whole hospital from January 1 to March 1, 2020, were enrolled. Demographic, clinical, radiological, laboratory, and treatment data were collected and analyzed. The effect of corticosteroids therapy on death and organ-failure complications of pneumonia were analyzed by logistic regression. Results: A total of 470 COVID-19 patients at the whole hospital were enrolled. According to the time of corticosteroids initiation and severity of illness, there were 159 patients stratified into critical ill group and 64% (102 of 159) patients received corticosteroids treatments. Ninety-four percent (166 of 176) of corticosteroids were methylprednisolone. The median cumulative corticosteroids dosage was 300 mg equivalent of methylprednisolone over a median duration of 6 days. Multivariate regression analysis showed that corticosteroids use did not affect the mortality. However, corticosteroids therapy at moderate cumulative doses (total exposure 480 mg to 1200 mg) was associated with deceased occurrence of organ-failure complications in critically ill COVID-19. Conclusions: Corticosteroids have no effect to mortality in COVID-19 patients. The moderate cumulative doses of corticosteroids might decrease organ-failure complications in critically ill COVID-19. Further large-scale randomized controlled trials are warranted to confirm our findings, until then use of corticosteroids should be used with caution COVID-19 patients.

Differential Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on COVID-19

Background: The effect of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) on the coronavirus disease 2019 (COVID-19) remains controversial from clinic evidence. Objectives: The objectives of this study were to report the major characteristics and clinical outcomes of COVID-19 patients treated with ACEIs and ARBs and compare the different effects of the two drugs for outcomes of COVID-19 patients. Methods: This is a retrospective, two-center case series of 198 consecutive COVID-19 patients with a history of hypertension. Results: Among 198 patients, 58 (29.3%) and 16 (8.1%) were on ARB and ACEI, respectively. Patients who were on ARB or ACEI/ARB had a significantly lower rate of severe illness and acute respiratory distress syndrome (ARDS) when compared with patients treated with ACEI alone or not receiving RAAS blocker (P < 0.05). The Kaplan–Meier survival curve showed that patients with ARB in their antihypertensive regimen had a trend toward a higher survival rate when compared with individuals without ARB (adjusted hazard ratio, 0.27;95% confidence interval [CI], 0.07–1.02;P = 0.054). The occurrence rates of severe illness, ARDS, and death were similar in the two groups regardless of receiving ACEI. The Cox regression analyses showed a better survival in the ARB group than the ACEI group (adjusted hazard ratio, 0.03;95% CI, 0.00–0.58;P = 0.02). Conclusions: Our data may provide that some evidence of using ARB, but not ACEI, was associated with a reduced rate of severe illness and ARDS, indicating their potential protective impact in COVID-19. Further large sample sizes and multiethnic populations are warranted to confirm our findings.

Comparison of Safety of Different Vaccine Boosters Following Two-Dose Inactivated Vaccines: A Parallel Controlled Prospective Study.

A vaccine booster to maintain high antibody levels and provide effective protection against COVID-19 has been recommended. However, little is known about the safety of a booster for different vaccines. We conducted a parallel controlled prospective study to compare the safety of a booster usingfour common vaccines in China. In total, 320 eligible participants who had received two doses of an inactivated vaccine were equally allocated to receive a booster of the same vaccine (Group A), a different inactivated vaccine (Group B), an adenovirus type-5 vectored vaccine (Group C), or a protein subunit vaccine (Group D). A higher risk of adverse reactions, observed up to 28 days after injection, was found in Groups C and D, compared to Group A, with odds ratios (OR) of 11.63 (95% confidence interval (CI): 4.22-32.05) and 4.38 (1.53-12.56), respectively. Recipients in Group C were more likely to report ≥two reactions (OR = 29.18, 95% CI: 3.70-229.82), and had a higher risk of injection site pain, dizziness, and fatigue. A gender and age disparity in the risk of adverse reactions was identified. Despite the majority of reactions being mild, heterologous booster strategies do increase the risk of adverse reactions, relative to homologous boosters, in subjects who have had two doses of inactive vaccine.

mTOR kinase is a therapeutic target for respiratory syncytial virus and coronaviruses.

Therapeutic interventions targeting viral infections remain a significant challenge for both the medical and scientific communities. While specific antiviral agents have shown success as therapeutics, viral resistance inevitably develops, making many of these approaches ineffective. This inescapable obstacle warrants alternative approaches, such as the targeting of host cellular factors. Respiratory syncytial virus (RSV), the major respiratory pathogen of infants and children worldwide, causes respiratory tract infection ranging from mild upper respiratory tract symptoms to severe life-threatening lower respiratory tract disease. Despite the fact that the molecular biology of the virus, which was originally discovered in 1956, is well described, there is no vaccine or effective antiviral treatment against RSV infection. Here, we demonstrate that targeting host factors, specifically, mTOR signaling, reduces RSV protein production and generation of infectious progeny virus. Further, we show that this approach can be generalizable as inhibition of mTOR kinases reduces coronavirus gene expression, mRNA transcription and protein production. Overall, defining virus replication-dependent host functions may be an effective means to combat viral infections, particularly in the absence of antiviral drugs.

Gene Knock-in by CRISPR/Cas9 and Cell Sorting in Macrophage and T Cell Lines.

Functional genomics studies of the immune system require genetic manipulations that involve both deletion of target genes and addition of elements to proteins of interest. Identification of gene functions in cell line models is important for gene discovery and exploration of cell-intrinsic mechanisms. However, genetic manipulations of immune cells such as T cells and macrophage cell lines using CRISPR/Cas9-mediated knock-in are difficult because of the low transfection efficiency of these cells, especially in a quiescent state. To modify genes in immune cells, drug-resistance selection and viral vectors are typically used to enrich for cells expressing the CRIPSR/Cas9 system, which inevitably results in undesirable intervention of the cells. In a previous study, we designed dual fluorescent reporters coupled to CRISPR/Cas9 that were transiently expressed after electroporation. This technical solution leads to rapid gene deletion in immune cells; however, gene knock-in in immune cells such as T cells and macrophages without the use of drug-resistance selection or viral vectors is even more challenging. In this article, we show that by using cell sorting to aid selection of cells transiently expressing CRISPR/Cas9 constructs targeting the Rosa26 locus in combination with a donor plasmid, gene knock-in can be achieved in both T cells and macrophages without drug-resistance enrichment. As an example, we show how to express human ACE2, a receptor of SARS-Cov-2, which is responsible for the current Covid-19 pandemic, in RAW264.7 macrophages by performing knock-in experiments. Such gene knock-in cells can be widely used for mechanistic studies.

A survey of laboratory biosafety and protective measures in blood transfusion departments during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: Thousands of healthcare workers (HCWs) have been infected with 2019 novel coronavirus pneumonia (COVID-19) during the COVID-19 pandemic. Laboratory personnel in blood transfusion departments may be infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) if laboratory biosafety protection is insufficient. Therefore, we investigated the current situation of laboratory biosafety protection in blood transfusion departments to determine how to improve the safety of laboratory processes. MATERIALS AND METHODS: An online survey was conducted in blood transfusion departments from 1st to 6th May 2020 in China. A total of 653 individuals completed the questionnaire. The questionnaire was designed with reference to COVID-19 laboratory biosafety summarized in Annex II. All responses were summarized using only descriptive statistics and expressed as frequencies and ratios [n (%)]. RESULTS: Most participants were concerned about COVID-19. Some participants had inadequate knowledge of COVID-19. Two participants stated that there were laboratory personnel infected with SARS-CoV-2 in their departments. A total of 31 (4.7%) participants did not receive any safety and security training. In terms of laboratory biosafety protection practices, the major challenges were suboptimal laboratory safety practices and insufficient laboratory conditions. CONCLUSION: The major deficiencies were insufficient security and safety training, and a lack of personal protective equipment, automatic cap removal centrifuges and biosafety cabinets. Consequently, we should enhance the security and safety training of laboratory personnel to improve their laboratory biosafety protection practices and ensure that laboratory conditions are sufficient to improve the safety of laboratory processes.

Association between the peripheral blood eosinophil counts and COVID-19: A meta-analysis.

BACKGROUND: The conclusions about the relationship between eosinophil counts and the severity of coronavirus disease 2019 (COVID-19) were controversial, so we updated the evidences and reassessed it. METHODS: We searched the PubMed, Cochrane library, Excerpta Medica Database, and Web of Science to compare the eosinophil counts about non-severe disease group (mild pneumonia, moderate pneumonia, non-critical disease and recovery group) and severe disease group (severe pneumonia, critical pneumonia, critical disease and death group) in COVID-19. RESULTS: A total of 1228 patients from 10 studies were included. Compared with non-severe group, severe group had strikingly lower average eosinophil counts (SMD 0.65, 95% confidence intervals [CI] 0.29-1.01; P < .001). The result of subgroup analysis of different countries showed SMD 0.66, 95% CI 0.26-1.06; P < .001. Another subgroup analysis between mild-moderate pneumonia versus severe-critical pneumonia showed SMD 0.69, 95% CI 0.25-1.13; P < .001, and no significant risk of publication bias (Begg test 0.063 and Egger test 0.057) in this subgroup. The heterogeneity was substantial, but the sensitivity analyses showed no significant change when individual study was excluded, which suggested the crediblity and stablity of our results. CONCLUSIONS: The eosinophil counts had important value as an indicator of severity in patients with COVID-19. PROSPERO REGISTRATION NUMBER: CRD42020205497.

Correlation analysis of coagulation dysfunction and liver damage in patients with novel coronavirus pneumonia: a single-center, retrospective, observational study.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) is currently breaking out worldwide. COVID-19 patients may have different degrees of coagulopathy, but the mechanism is not yet clear. We aimed to analyse the relationship between coagulation dysfunction and liver damage in patients with COVID-19. METHODS: A retrospective analysis of 74 patients with COVID-19 admitted to the First People's Hospital of Yueyang from 1 January to 30 March 2020 was carried out. According to the coagulation function, 27 cases entered the coagulopathy group and 47 cases entered the control group. A case control study was conducted to analyse the correlation between the occurrence of coagulation dysfunction and liver damage in COVID-19 patients. RESULTS: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), markers of liver damage, were positively correlated with coagulopathy (p = 0.039, OR 2.960, 95% CI 1.055-8.304; and p = 0.028, OR 3.352, 95% CI 1.137-9.187). Alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), and total bilirubin (TBIL) were not statistically correlated with coagulopathy. According to the diagnosis and treatment plan, the included cases were classified into mild, moderate, severe, and critical. The results showed that the occurrence of coagulation dysfunction had no statistical correlation with the severity of COVID-19. CONCLUSION: Coagulation dysfunction in patients with COVID-19 is closely related to liver damage. A longer course of the disease may cause a vicious circle of coagulopathy and liver damage. Clinicians need to closely monitor coagulation and liver function tests and to give prophylactic or supportive therapy when needed.

Coagulation and immune function indicators for monitoring of coronavirus disease 2019 and the clinical significance. / 2019å† çŠ¶ç— æ¯’ç— å‡è¡€å’Œå ç–«åŠŸèƒ½æŒ‡æ ‡çš„ç›‘æµ‹åŠä¸´åºŠæ„ä¹‰.

OBJECTIVES: To explore the significance of coagulation and immune function indicators in clinical diagnosis and treatment of coronavirus disease 2019 (COVID-19). METHODS: All patients with COVID-19 diagnosed and treated in First People's Hospital of Yueyang from January to March 2020 were enrolled. The general data of patients were collected. The patients were assigned into a light group (n=20), an ordinary group (n=33), a severe group (n=23), and a critically severe group (n=7) according to the severity of the disease. Coagulation and immune function indicators of each group were compared, and the relevance of coagulation and immune function indicators was analyzed. RESULTS: The age of COVID-19 patients in Yueyang City was mainly between 45 and 65 years old. There was a significant difference in the coagulation function and immune-related indicators in each group of patients (all P<0.05). CONCLUSIONS: There are some abnormalities in coagulation and immune function in patients with COVID-19, which possess significance for clinical diagnosis and treatment of the disease.

Optimization, Prevention and Control Measures of PET/CT Examination and Nursing Workflow During the Prevention and Control of Novel Coronavirus Pneumonia

The PET/CT examination in nuclear medicine subject has many procedures involved many links and workplaces, and the management requirements for patients are complex. Patients need to stay in a relatively closed environment for a long time after the injection of radio pharmaceuticals, so the risk of cross-infection between medical staff and patients, and between patients is high. In novel coronavirus pneumonia (NCP) during the prevention and control, it’s very important for patients carried out PET/CT examination to formulate emergency preplans for prevention, control and optimize the workflow, take necessary control measures, make the medical staff of personal protection. We have to do well for the patients of the correct health education, reduce exposure risk, reduce the cross infection, and guarantee the quality of nuclear medicine inspection and safety.