Timing and Depth Selection for Sedated Gastroscopy After SARS-CoV-2 Infection—A Retrospective Cohort Study (preprint)

Background Sedated gastroscopy is a crucial procedure for patients with upper respiratory infections. SARS-CoV-2-infected patients are more susceptible to anesthesia-related complications, such as edema, pharyngeal mucosa congestion, laryngospasm, and pulmonary infections.Methods We retrospectively analyzed a total of 386 patients who underwent sedated gastroscopy at the Affiliated Hospital of Qingdao University during the SARS-CoV-2 infection period. The patients were divided into three groups based on SARS-CoV-2 status: Negative (N), Two-week post-SARS-CoV-2 infection (T), and Three-week post-SARS-CoV-2 infection (Th) groups. Based on the anesthesia method, patients were divided into mild/moderate sedation and deep sedation/general anesthesia groups. Additionally, patients were categorized into groups based on COVID-19 severity and vaccination status. We recorded the laryngeal mucosal conditions, the occurrence rates of adverse reactions such as coughing, laryngospasm, and transient oxygen desaturation during the examination, as well as the satisfaction of patients and endoscopists were recorded.Results The T group displayed a significantly higher occurrence rate of adverse reactions when compared to the N and Th group, with decreased satisfaction levels of patients and endoscopists. In the T group, the occurrence rate of adverse reactions was higher in mild to moderate sedation than in deep sedation/general anesthesia methods, while patient and endoscopist satisfaction was lower. In the Th group, there was no statistically significant difference in the examination success rate or patient satisfaction between the mild/moderate sedation and deep sedation/general anesthesia methods; however, endoscopist satisfaction was lower with mild/moderate sedation method than deep sedation/general anesthesia method. There was a significant difference in the gastroscopy success rates of patients with different COVID-19 classifications. A significant difference was observed in the gastroscopy success rates among patients with different vaccination statuses.Conclusions Sedated gastroscopy post-three weeks of SARS-CoV-2 infection is safe. Moreover, using a deep sedation/general anesthesia method for sedated gastroscopy in SARS-CoV-2-infected patients within three weeks is significantly safer.

Endothelial SARS-CoV-2 infection is not the underlying cause of COVID19-associated vascular pathology in mice (preprint)

Endothelial damage and vascular pathology have been recognized as major features of COVID-19 since the beginning of the pandemic. Two main theories regarding how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) damages endothelial cells and causes vascular pathology have been proposed: direct viral infection of endothelial cells or indirect damage mediated by circulating inflammatory molecules and immune mechanisms. However, these proposed mechanisms remain largely untested in vivo. Here, we utilized a set of new mouse genetic tools1 developed in our lab to test both the necessity and sufficiency of endothelial human angiotensin-converting enzyme 2 (hACE2) in COVID19 pathogenesis. Our results demonstrate that endothelial ACE2 and direct infection of vascular endothelial cells does not contribute significantly to the diverse vascular pathology associated with COVID-19.

Single-cell transcriptome landscape of circulating CD4+ T cell populations in human autoimmune diseases (preprint)

CD4+ T cells are a key mediator of various autoimmune diseases; however, how they contribute to disease development remains obscure primarily because of their cellular heterogeneity. Here, we evaluated CD4+ T cell subpopulations by decomposition-based transcriptome characterization together with canonical clustering strategies. This approach identified 12 independent transcriptional gene programs governing whole CD4+ T cell heterogeneity, which can explain the ambiguity of canonical clustering. In addition, we performed a meta-analysis using public single-cell data sets of over 1.8M peripheral CD4+ T cells from 953 individuals by projecting cells onto the reference and cataloged cell frequency and qualitative alterations of the populations in 20 diseases. The analyses revealed that the 12 transcriptional programs were useful in characterizing each autoimmune disease and predicting its clinical status. Moreover, genetic variants associated with autoimmune diseases showed disease-specific enrichment within the 12 gene programs. The results collectively provide a landscape of single-cell transcriptomes of CD4+ T cell subpopulations involved in autoimmune disease.

A versatile integrated tube for rapid and visual SARS-CoV-2 detection

The coronavirus disease 2019 (COVID-19) caused by novel severe acute respiratory coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide. Rapid and widespread testing is essential to promote early intervention and curb the ongoing COVID-19 pandemic. Current gold standard reverse transcription-polymerase chain reaction (RT-PCR) for detecting SARS-CoV-2 is restricted to professional laboratories and well-trained personnel, thus, limiting its widespread use in resource-limited conditions. To overcome these challenges, we developed a rapid and convenient assay using a versatile integrated tube for the rapid and visual detection of SARS-CoV-2. The reaction conditions of the method were optimized using SARS-CoV-2 RNA standards and the sensitivity and specificity were further determined. Finally, it was verified on clinical specimens. The assay was completed within 40 min, and the result was visible by the naked eye. The limits of detection (LODs) for the target ORF1ab and N genes were 50 copies/μl. No cross-reactivity was observed with the RNA standard samples of four respiratory viruses or clinical samples of common respiratory viral infections. Ninety SARS-CoV-2 positive and 30 SARS-CoV-2 negative patient specimens were analyzed. We compared these results to both prior and concurrent RT-PCR evaluations. As a result, the overall sensitivity and specificity for detection SARS-CoV-2 were 94.5 and 100.0%, respectively. Conclusion The integrated tube assay has the potential to provide a simple, specific, sensitive, one-pot, and single-step assay for SARS-CoV-2.

Asymmetric Multifractal Analysis of the Chinese Energy Futures and Energy Stock Markets under the Impact of COVID-19

The volatility and cross-correlations of the energy market and the stock market during the COVID-19 pandemic have been paid close attention by scholars and investors. In this paper, we use the asymmetric multifractal analysis methods to study the fluctuation characteristics, market risks and cross-correlations of the Chinese energy futures market (EFM) and two energy stock markets before and after the COVID-19 outbreak, while the return series of Shanghai fuel oil futures, CSI Energy Index and CSI Mainland New Energy Theme Index are considered. The empirical evidences indicate that the auto- and cross-correlations of the three markets have the asymmetric multifractality, and that the multifractality of the cross-correlations is mainly caused by the fat-tailed distribution of the original series. After the COVID-19 outbreak, the risks of both the traditional energy stock market in the uptrend and the entire new energy stock market become larger, while those of the entire EFM become smaller. In addition, the COVID-19 pandemic has increased the multifractality of the cross-correlations between the energy futures and energy stock markets when the EFM is in downward trend. [ FROM AUTHOR]

Does Cross-Border E-Commerce Promote Economic Growth? Empirical Research on China’s Pilot Zones

Whether the construction of China’s cross-border e-commerce (CBEC) comprehensive pilot zones can promote economic growth and social sustainable development is an important question worthy of discussion. This paper uses the difference-in-differences (DID) method to test the impact of the establishment of CBEC comprehensive pilot zones on economic growth and discusses the impact mechanism. The results are as follows. (1) The construction of CBEC comprehensive pilot zones can promote economic growth. After testing with parallel trend, placebo, and other robustness methods, the results are still valid. (2) The economic promotion effect of the construction of CBEC comprehensive pilot zones will be more evident in the coastal and eastern regions. The economic promotion effect of the first, second, and third batch of CBEC comprehensive pilot zones is clear. (3) The main ways that the construction of CBEC comprehensive pilot zones can facilitate economic growth are through urban digitalization, trade openness, and information service industry agglomeration.

In situ structure and dynamics of an alphacoronavirus spike protein by cryo-ET and cryo-EM

Porcine epidemic diarrhea (PED) is a highly contagious swine disease caused by porcine epidemic diarrhea virus (PEDV). PED causes enteric disorders with an exceptionally high fatality in neonates, bringing substantial economic losses in the pork industry. The trimeric spike (S) glycoprotein of PEDV is responsible for virus-host recognition, membrane fusion, and is the main target for vaccine development and antigenic analysis. The atomic structures of the recombinant PEDV S proteins of two different strains have been reported, but they reveal distinct N-terminal domain 0 (D0) architectures that may correspond to different functional states. The existence of the D0 is a unique feature of alphacoronavirus. Here we combined cryo-electron tomography (cryo-ET) and cryo-electron microscopy (cryo-EM) to demonstrate in situ the asynchronous S protein D0 motions on intact viral particles of a highly virulent PEDV Pintung 52 strain. We further determined the cryo-EM structure of the recombinant S protein derived from a porcine cell line, which revealed additional domain motions likely associated with receptor binding. By integrating mass spectrometry and cryo-EM, we delineated the complex compositions and spatial distribution of the PEDV S protein N-glycans, and demonstrated the functional role of a key N-glycan in modulating the D0 conformation. Hsu and co-workers integrate cryo-electron tomography, cryo-electron microscopy and mass spectrometry to reveal the structural polymorphism of a pig coronavirus spike protein within intact viral particles, and how glycosylation modulates the conformational changes pertinent to host recognition.

SARS-CoV-2 specific antibody levels after a third dose of inactivated vaccine among 91 medical staff in Chengdu

Objective: To analysis the production of SARS-CoV-2 antibody among medical staff in Public Health Clinical Center of Chengdu 1 month after a third dose of inactivated vaccine (booster shot), and to compare the SARS-CoV-2 antibody among COVID-19 patients after immunization, in order to analyze the effect of the booster shot.

Understanding systemic risk induced by climate change

The systemic risk induced by climate change represents one of the most prominent threats facing humanity and has attracted increasing attention since the outbreak of the COVID-19 pandemic at the end of 2019. The existing literature highlights the importance of systemic risk induced by climate change, but there are still deficiencies in understanding its dynamics and assessing the risk. Aiming to bridge this gap, this study develops a theoretical framework and employs two cases to illustrate the concept, origin, occurrence, propagation, evolution, and assessment framework of systemic risk induced by climate change. The key findings include: 1) systemic risk induced by climate change derives from the rapid growth of greenhouse gas emissions, increasingly complex connections among different socioeconomic systems, and continuous changes in exposure and vulnerability;2) systemic risk induced by climate change is a holistic risk generated by the interconnection, interaction, and dynamic evolution of different types of single risks, and its fundamental, defining feature is cascading effects. The extent of risk propagation and its duration depend on the characteristics of the various discrete risks that are connected to make up the systemic risk;3) impact domains, severity of impact, and probability of occurrences are three core indicators in systemic risk assessment, and the impact domains should include the economy, society, homeland security, human health, and living conditions. We propose to deepen systemic risk research from three aspects: to develop theories to understand the mechanism of systemic risk;to conduct empirical research to assess future risks;and to develop countermeasures to mitigate the risk.

Compound Lidocaine cream combined with tetracaine prevents cough reaction of patients with general anesthesia caused by extubation: a randomised controlled trial (preprint)

Background: Coughing response caused by tracheal extubation is the most common in general anesthesia patients with tracheal intubation during recovery from anesthesia. However, high aerosol production by coughing during recovery from general anesthesia in patients with respiratory infections (especially COVID-19) is one of the highest risk factors for infection among healthcare workers. Application of local anesthetics to the endotracheal tube is an effective method to reduce the choking reaction. The most commonly used anaesthetics are compound Lidocaine cream and tetracaine injection. However, there is still a certain number of choking reactions in the clinic when the two anaesthetics are used alone. We speculate that the combined application of compound Lidocaine cream and tetracaine will play a better role in prevent coughing response caused by tracheal extubation.Methods: A total of 211 patients, who had undergone laparoscopic cholecystectomy or cholecystectomy combined with common bile duct exploration under general anesthesia, were randomly assigned to Group C (saline injection, 53 cases), Group L(compound lidocaine cream, 52 cases), Group T (tetracaine, 52 cases) and Group F (compound lidocaine cream combined tetracaine, 54 cases). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), levels of epinephrine and levels of norepinephrine were recorded or measured immediately before extubation and one minute after extubation. In addition, endotracheal tube tolerance, the incidence of bucking, the incidence of agitation, the active extubation rate, the incidence of postoperative pharyngeal pain and the incidence of postoperative cough were analyzed. Results: Blood pressure and heart rate as well as blood concentrations of epinephrine and norepinephrine were significantly higher in the group C compared with the every other group at the time of extubation as well as 1 min after extubation (P < 0.001). And group F significantly reduced the Blood pressure and heart rate as well as blood concentrations of epinephrine and norepinephrine compared group L or group T (P < 0.05, P < 0.01 or P < 0.001). When the patients emerged from general anesthesia, 96% of the group C had cough caused by sputum aspiration and extubation, which was significantly reduced by group L (61.5%, P < 0.001), group T (75%, P < 0.05) and group F (22.2%, P < 0.001), furthermore, group F significantly reduced the incidence of cough compared group L or group T (P < 0.01). Assessment of endotracheal tube tolerance, the score in the group C ((1, 3) 4, P < 0.001) is higher than group L ((0, 1) 2), group T ((0, 1.25) 3) and group F ((0, 0) 1), furthermore, group F significantly reduced the score compared group L or group T (P < 0.05, P < 0.01, respectively). The incidence of agitation and the active extubation rate were also higher in group C (96.2%, 71.7%, respectively, P < 0.001) than group L (48.1%, 15.4%, respectively), group T (61.5%, 26.9%，respectively) and group F (17.3%, 7.7%，respectively), furthermore，group F significantly reduced the incidence of cough compared group L or group T (P < 0.05 or P < 0.01). In addition, the incidence of postoperative pharyngeal pain and the incidence of postoperative cough were no statistical difference between every groupConclusions: Compound Lidocaine cream combined tetracaine may be a more advantageous approach for preventing choking and stabilizing circulation during extubation in emergence from general anesthesia, which may play an important role in preventing medical staff from contracting respiratory infectious diseases. Trial registration: Chinese Clinical Trial Registry: ChiCTR2200058429 (registration date: 09-04-2020) “retrospectively registered”. 

Nutritional therapy for critical coronavirus disease 2019 patients: a case report (preprint)

Background: An ongoing outbreak of coronavirus disease 2019 (COVID-19) is spreading, there are few reports on exploring individualized nutritional therapy for critical coronavirus disease 2019 (COVID-19) patients. Case presentation: To explore individualized nutritional therapy for critical coronavirus disease 2019 (COVID-19) patients.A nutritional treatment plan was created through nutritional risk screening and nutritional assessment, and an individualized nutritional treatment was implemented through multidisciplinary collaboration. The patient’s gastrointestinal symptoms were corrected, and her nutrition-related indicators such as albumin and body weight were improved. She was cured and discharged. Conclusion: Nutritional therapy is beneficial to improve the nutritional status and clinical outcome of critical COVID- 19 patients.

SARS-CoV-2 infection of olfactory epithelial cells and neurons drives acute lung injury and lethal COVID-19 in mice (preprint)

Lethal COVID-19 is associated with respiratory failure that is thought to be caused by acute respiratory distress syndrome (ARDS) secondary to pulmonary infection. To date, the cellular pathogenesis has been inferred from studies describing the expression of ACE2, a transmembrane protein required for SARS-CoV-2 infection, and detection of viral RNA or protein in infected humans, model animals, and cultured cells. To functionally test the cellular mechanisms of COVID-19, we generated hACE2fl animals in which human ACE2 (hACE2) is expressed from the mouse Ace2 locus in a manner that permits cell-specific, Cre-mediated loss of function. hACE2fl animals developed lethal weight loss and hypoxemia within 7 days of exposure to SARS-CoV-2 that was associated with pulmonary infiltrates, intravascular thrombosis and patchy viral infection of lung epithelial cells. Deletion of hACE2 in lung epithelial cells prevented viral infection of the lung, but not weight loss, hypoxemia or death. Inhalation of SARS-CoV-2 by hACE2fl animals resulted in early infection of sustentacular cells with subsequent infection of neurons in the neighboring olfactory bulb and cerebral cortex-- events that did not require lung epithelial cell infection. Pharmacologic ablation of the olfactory epithelium or Foxg1Cre mediated deletion of hACE2 in olfactory epithelial cells and neurons prevented lethality and neuronal infection following SARS-CoV-2 infection. Conversely, transgenic expression of hACE2 specifically in olfactory epithelial cells and neurons in Foxg1Cre; LSL-hACE2 mice was sufficient to confer neuronal infection associated with respiratory failure and death. These studies establish mouse loss and gain of function genetic models with which to genetically dissect viral-host interactions and demonstrate that lethal disease due to respiratory failure may arise from extrapulmonary infection of the olfactory epithelium and brain. Future therapeutic efforts focused on preventing olfactory epithelial infection may be an effective means of protecting against severe COVID-19.

Comparative Study of HRCT Imaging Characteristics of Psittaci Pneumonia and COVID-19 Pneumonia (preprint)

Backgroud : Both Chlamydia psittaci and COVID-19 virus can cause lung inflammation, which manifests extremely similarly in clinical symptoms and imaging. Especially during the epidemic of COVID-19, psittacosis pneumonia is easily misdiagnosed as COVID-19 pneumonia. The identification of the chest imaging between the two diseases is of special significance when the epidemiological contact history is unclear, and the etiology and nucleic acid test results are not available. This study conducts to compare the imaging characteristics on chest high-resolution CTs (HRCT) between patients with psittaci pneumonia and COVID-19 pneumonia. Methods: : A retrospective analysis of the imaging characteristics on chest HRCTs of 10 psittaci pneumonia patients and 13 COVID-19 pneumonia patients. The similarities and differences in HRCT images of patients with psittaci pneumonia and COVID-19 pneumonia were analyzed. Results: : HRCT showed that among the 10 psittaci pneumonia patients, 8 cases (80.00%) had single lobe involvement, and 2 cases (20.00%) had multiple lobe involvement. Among the 13 COVID-19 pneumonia patients, 2 cases had single lobe involvement (15.38%), and 11 cases had multiple lobe involvement (84.62%). The types of lesions in 10 psittaci pneumonia patients included simple consolidation in 5 cases (50.00%), and ground-glass opacity (GGO) with consolidation in 5 cases (50.00%). The types of lesions in 13 COVID-19 pneumonia patients included simple GGO in 6 cases (46.15%), GGO with consolidation in 4 cases (30.77%), GGO with paving stone sign in 2 cases (15.38%), and simple consolidation in 1 case (7.69%). Lymphadenopathy was observed in 1 psittaci pneumonia patient (10.00%) and 1 COVID-19 pneumonia patient (7.69%). Among the 10 psittaci pneumonia patients, 8 cases (80.00%) had bronchial inflation, and 6 patients (60.00%) had pleural effusion. Among the 13 COVID-19 pneumonia patients, 5 patients (38.46%) showed signs of bronchial inflation, while no pleural effusion was observed in 13 patients. Conclusion: : Chest HRCTs can distinguish COVID-19 pneumonia from psittaci pneumonia, and can provide early diagnoses of these two diseases.

Using social media to mine and analyze public opinion related to COVID-19 in China

The outbreak of Corona Virus Disease 2019 (COVID-19) is a grave global public health emergency. Nowadays, social media has become the main channel through which the public can obtain information and express their opinions and feelings. This study explored public opinion in the early stages of COVID-19 in China by analyzing Sina-Weibo (a Twitter-like microblogging system in China) texts in terms of space, time, and content. Temporal changes within one-hour intervals and the spatial distribution of COVID-19-related Weibo texts were analyzed. Based on the latent Dirichlet allocation model and the random forest algorithm, a topic extraction and classification model was developed to hierarchically identify seven COVID-19-relevant topics and 13 sub-topics from Weibo texts. The results indicate that the number of Weibo texts varied over time for different topics and sub-topics corresponding with the different developmental stages of the event. The spatial distribution of COVID-19-relevant Weibo was mainly concentrated in Wuhan, Beijing-Tianjin-Hebei, the Yangtze River Delta, the Pearl River Delta, and the Chengdu-Chongqing urban agglomeration. There is a synchronization between frequent daily discussions on Weibo and the trend of the COVID-19 outbreak in the real world. Public response is very sensitive to the epidemic and significant social events, especially in urban agglomerations with convenient transportation and a large population. The timely dissemination and updating of epidemic-related information and the popularization of such information by the government can contribute to stabilizing public sentiments. However, the surge of public demand and the hysteresis of social support demonstrated that the allocation of medical resources was under enormous pressure in the early stage of the epidemic. It is suggested that the government should strengthen the response in terms of public opinion and epidemic prevention and exert control in key epidemic areas, urban agglomerations, and transboundary areas at the province level. In controlling the crisis, accurate response countermeasures should be formulated following public help demands. The findings can help government and emergency agencies to better understand the public opinion and sentiments towards COVID-19, to accelerate emergency responses, and to support post-disaster management.

Can gold be a safe haven during the COVID-19 pandemic? A quantile causality analysis

This study investigates the causal relationship between the coronavirus disease (COVID-19) pandemic and the gold market through a quantile causality framework. It examines whether gold can be a safe haven for funds during the spread of COVID-19 using daily data from January 23, 2020 to July 10, 2020. The empirical findings suggest that the COVID-19 pandemic and the gold market have a bi-directional causality only at lower and higher quantiles. However, gold acts as a safe haven for investors only under higher quantiles (0.95). It means that only in a high quantile, gold be a safe haven during the COVID-19 pandemic.

Based on Transcriptome Sequencing: Clinicians Need to Pay Attention to Fever Caused by Common Respiratory Pathogens During the Global Outbreak of COVID-19 (preprint)

Objectives:During the COVID-19 pandemic, clinicians and public health decision-makers especially focus on fever patients. Other common pathogens that may cause fever are easily overlooked. We aimed to describe the pathogen infection and epidemic trend of non-SARS-CoV-2 occurring in hospitalized patients.Methods:An observational cohort study of 733 consecutive patients admitted to Hospital Clinic of the Second Xiangya Hospital for COVID-19. All samples of a pharyngeal swab from patients with fever have been tested for nucleic acid and immune antigens of SARS-CoV-2 and Influenza A/B virus. 649 fever patients have been tested for nucleic acid in ten respiratory pathogens. Macrotranscriptome sequencing was performed on 26 samples.Results:Of a total of 733 patients with fever, 2.05% patients had confirmed SARS-CoV-2 infections. Fever patients with common respiratory pathogens in fever patients was 8.78%. There is no integration phenomenon between SARS-Cov-2 and the human genome. SARS-CoV-2 positive samples will also be infected with other viruses, especially adenovirus. Macrotranscript analysis showed that there was no significant difference in the species and genus levels of pathogens between Covid-19 patients and other fever patients. The main pathways that affect human metabolism after SARS-Cov-2 infection are the Calvin-Benson-Bassham cycle, pyrimidine deoxyribonucleotides de novo biosynthesis I and D-galactose degradation V.Conclusions:Most patients have a fever caused by common respiratory pathogens. Clinicians still need to pay more attention to infections of common respiratory pathogens in addition to SARS-CoV-2. China's public health measures to stop the spread of the epidemic have proven effective.

Protein corona critically affects the bio-behaviors of SARS-CoV-2 (preprint)

The outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a worldwide public health crisis. When the SARS-CoV-2 enters the biological fluids in the human body, different types of biomolecules (in particular proteins) may adsorb on its surface and alter its infection ability. Although great efforts have recently been devoted to the interaction of the specific antibodies with the SARS-CoV-2, it still remains largely unknown how the other serum proteins affect the infection of the SARS-CoV-2. In this work, we systematically investigate the interaction of serum proteins with the SARS-CoV-2 RBD by the molecular docking and the all-atom molecular dynamics simulations. It is found that the non-specific immunoglobulin (Ig) indeed cannot effectively bind to the SARS-CoV-2 RBD while the human serum albumin (HSA) may have some potential of blocking its infection (to ACE2). More importantly, we find that the RBD can cause the significant structural change of the Apolipoprotein E (ApoE), by which SARS-CoV-2 may hijack the metabolic pathway of the ApoE to facilitate its cell entry. The present study enhances the understanding of the role of protein corona in the bio-behaviors of SARS-CoV-2, which may aid the more precise and personalized treatment for COVID-19 infection in the clinic.