COVID-19 and membranous nephropathy: observational and Mendelian randomization analyses (preprint)

Membranous nephropathy (MN) imposes a substantial burden of illness and death. However, a systematic assessment of the impact of the COVID-19 pandemic on MN incidence has not yet been conducted. This research is an observational cohort study conducted retrospectively. The kidney biopsy results of two medical institutions, including our hospital, were reviewed for the period between January 2016 and May 2023. Relevant statistical analysis of different glomerular diseases was performed based on the corresponding pathological diagnoses. The aim was to compare the incidence changes of different glomerular diseases before and during the COVID-19 pandemic. Our focus was on investigating the changes in the incidence rate of MN and attempting to uncover the causal effects between varying degrees of COVID-19 and MN utilizing bidirectional Mendelian randomization (MR) using GWAS data from European and Asian ancestry. We found that the incidence of MN decreased by 3.6% during the COVID-19 pandemic compared to the period before the onset of the COVID-19 pandemic(P = 0.026). However, after Bonferroni correction, the change in incidence did not reach a significant p-value(P > 0.05/2), and the overall incidence of glomerular diseases did not show a significant change (P = 0.364). Additionally, the Mendelian randomization analysis indicated no significant causality between COVID-19 (critical illness, susceptibility, severe infection, hospitalization, and severity) and MN (no significance, PBonferroni>0.05).The results of this preliminary study suggest that the incidence rate of MN remained relatively stable during the COVID-19 pandemic. Furthermore, our genetic perspective Mendelian randomization analysis has furnished additional evidence contradicting any causal relationship between varying degrees of COVID-19 infection and MN.

Applying the Push-Pull Mooring to Explore Consumers' Shift from Physical to Online Purchases of Face Masks

In response to the emergency management caused by COVID-19, Taiwan began to impose a name-based rationing system for the purchase of face masks by having consumers visit physical stores and preorder them online. By doing so, the risk of face mask shortages caused by panic buying was reduced. To understand consumers' willingness to switch from buying face masks at physical stores to preordering them online, we used a push-pull-mooring (PPM) model to measure related dimensions. We administered an online questionnaire survey and collected 233 valid responses. In the present study, perceived risk (including time risk, psychological risk and social risk) was treated as a second-order formative indicator, while pull effect was measured by the variables of critical mass and alternative attraction. Mooring effect was measured by switching cost. Through structural equation modeling (SEM), perceived risk, as well as critical mass and alternative attraction, had a significant effect on switching intention, while switching cost had no significant relationship with switching intention. This study investigated whether perceived risk (time risk, psychological risk and social risk), critical mass, alternative attraction and switching cost can serve as references for purchase behaviors amid future emergency management, through the prism of population migration theory, and proposed recommendations for their promotion and implementation.

The Effects of Pulsed Electric Field On The Interaction Between SARS-Cov-2 And Human ACE2: Y505 Is A Key Target (preprint)

A novel coronavirus has rapidly spread to almost every country in the world, causing over 233 million confirmed cases of coronavirus disease 2019 (COVID-19) and over 209,761,242 deaths by late September 2021. Binding the receptor binding domain (RBD) to the host cell surface receptor protein, angiotensin converter enzyme (ACE2), is a key step in virus infection. In this study, we applied a pulsed electric field to the RBD/ACE2 complex based on molecular dynamics simulation and demonstrated that the electric field affects the structure and binding affinity of the complex. Additionally, residue Y505 is the crucial medium for the effects of electric field on the complex. Overall, these results may help apply an external electric field to virus suppression.

Research on Kinematics Analysis and Trajectory Planning of Novel EOD Manipulator

To address the problems of mismatch, poor flexibility and low accuracy of ordinary manipulators in the complex special deflagration work process, this paper proposes a new five-degree-of-freedom (5-DOF) folding deflagration manipulator. Firstly, the overall structure of the explosion-expulsion manipulator is introduced. The redundant degrees of freedom are formed by the parallel joint axes of the shoulder joint, elbow joint and wrist pitching joint, which increase the flexibility of the mechanism. Aiming at a complex system with multiple degrees of freedom and strong coupling of the manipulator, the virtual joint is introduced, the corresponding forward kinematics model is established by D–H method, and the inverse kinematics solution of the manipulator is derived by analytical method. In the MATLAB platform, the workspace of the manipulator is analyzed by Monte Carlo pseudo-random number method. The quintic polynomial interpolation method is used to simulate the deflagration task in joint space. Finally, the actual prototype experiment is carried out using the data obtained by simulation. The trajectory planning using the quintic polynomial interpolation method can ensure the smooth movement of the manipulator and high accuracy of operation. Furthermore, the trajectory is basically consistent with the simulation trajectory, which can realize the work requirements of putting the object into the explosion-proof tank. The new 5-DOF folding deflagration manipulator designed in this paper has stable motion and strong robustness, which can be used for deflagration during the COVID-19 epidemic.

Visualization of Vaccine Dynamics with Quantum Dots for Immunotherapy

The direct visualization of vaccine fate is important to investigate its immunoactivation process in order to elucidate the detailed molecular reaction process at single-molecular level. Yet, visualization of the spatiotemporal trafficking of vaccines remains poorly explored. Here, we show that quantum dot (QD) nanomaterials allow for monitoring vaccine dynamics and for amplified immune response. Synthetic QDs enable efficient conjugation of antigen and adjuvants to target tissues and cells, and non-invasive imaging the trafficking dynamics to lymph nodes and cellular compartments. The nanoparticle vaccine elicits potent immune responses and anti-tumor efficacy alone or in combination with programmed cell death protein 1 blockade. The synthetic QDs showed high fluorescence quantum yield and superior photostability, and the reliable and long-term spatiotemporal tracking of vaccine dynamics was realized for the first time by using the synthetic QDs, providing a powerful strategy for studying the immune response and for evaluating the vaccine efficacy.

Azacytidine targeting SARS-CoV-2 viral RNA as a potential treatment for COVID-19 (preprint)

The COVID-19 pandemic is a global health disaster. Moreover, emerging mutated virus strains present an even greater challenge for existing vaccines and medications. One possible solution is to design drugs based on the properties of virus epigenome, which are more common among coronaviruses. Here, we reported an FDA-approved drug for myelodysplastic syndrome, azacytidine (5Aza), limited virus infection and protected mice against SARS-CoV-2. We demonstrated that this antiviral effect is related to 5Aza incorporation into viral RNA, which disrupt m5C RNA methylation modification profile. This work suggests that targeting viral epigenomes is a viable therapeutic strategy, potentially opening new pathways for treating COVID-19.

A Chinese host genetic study discovered type I interferons and causality of cholesterol levels and WBC counts on COVID-19 severity (preprint)

As of early May 2021, the ongoing pandemic COVID-19 has caused over 160 million of infections and over 3 million deaths worldwide. Many risk factors, such as age, gender, and comorbidities, have been studied to explain the variable symptoms of infected patients. However, these effects may not fully account for the diversity in disease severity. Here, we present a comprehensive analysis of a broad range of patients laboratory and clinical assessments to investigate the genetic contributions to COVID-19 severity. By performing GWAS analysis, we discovered several concrete associations for laboratory features. Based on these findings, we performed Mendelian randomization (MR) analysis to investigate the causality of laboratory traits on disease severity. From the MR study, we identified two causal traits, cholesterol levels and WBC counts. The functional gene related to cholesterol levels is ApoE and people with particular ApoE genotype are more likely to have higher cholesterol levels, facilitating the process that SARS-CoV-2 binds on its receptor ACE2 and aggravating COVID-19 disease. The functional gene related to WBC counts is MHC system that plays a central role in the immune system. The host immune response to the SARS-CoV-2 infection greatly affects the patients severity status and clinical outcome. Additionally, our gene-based and GSEA analysis revealed interferon pathways, including type I interferon receptor binding, regulation of IFNA signaling, and SARS coronavirus and innate immunity. We hope that our work will make a contribution in studying the genetic mechanisms of disease illness and serve as useful reference for the clinical diagnosis and treatment of COVID-19.

Pulmonary Dysfunction in Patients Recovered from COVID-19 Pneumonia: A 6-Month Follow-up Study (preprint)

Objectives: This study investigates the clinical features and pulmonary functions of COVID-19 pneumonia survivors at 3 or 6 months after diagnosis in the Heilongjiang Province, China.Methods: Forty-six patients with COVID-19 pneumonia diagnosed since February 2020 were enrolled in this study for follow-up in July 2020. These patients were categorized into three groups: Group A (n=24) and Group B (n=11) who were diagnosed with moderate or severe pneumonia and followed up at three months after diagnosis; Group C (n=11) who were diagnosed with severe pneumonia and followed up at six months after diagnosis. Data on pulmonary function, arterial blood gas analysis, chest CT, blood test, antibody test, and health-related quality of life during hospitalization and at the follow-up visits were collected and analyzed. Results: Abnormal PO2 (A-a) was more prevalent in severe cases (Group B and C) than in moderate cases (Group A). Pulmonary dysfunction was common in this cohort. Abnormal CT scores of severe cases (Group B and C) were significantly higher than that of moderate cases (Group A). During the follow-up, lung abnormalities gradually resolved in the first 3 months (Group A and B), however, further resolution was not significant from 3 months to 6 months (Group B and C). Conclusion: Although pulmonary interstitial changes due to COVID-19 pneumonia gradually reverse over time, pulmonary dysfunction is common and appears to persist at least up to 6 months in patients recovered from COVID-19 pneumonia.

Dynamics of the Upper Respiratory Tract Microbiota and Its Association with Fatality in COVID-19 Patients (preprint)

Background: The pandemic of Coronavirus disease 2019 (COVID-19) is ongoing globally, which is a big challenge for public health. Alteration of human microbiota had been observed in COVID-19. However, it is unknown how the microbiota is associated with the fatality in COVID-19.Methods: We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 COVID-19 patients recruited in the LOTUS clinical trial (Registration number: ChiCTR2000029308) (including 39 deceased patients), and 95 healthy controls from the same geographic area.Findings: The upper respiratory tract (URT) microbiota in COVID-19 patients differed from that in healthy controls, while deceased patients possessed a more distinct microbiota. Streptococcus was enriched in recovered patients, whereas potential pathogens, including Candida and Enterococcus, were more abundant in deceased patients. Moreover, the microbiota dominated by Streptococcus was more stable than that dominated by other species. In contrast, the URT microbiota in deceased patients showed a more significant alteration and became more deviated from the norm after admission. The abundance of Streptococcus on admission, particularly that of S. parasanguis, was identified as a strong predictor of fatality by Cox and L1 regularized logistic regression analysis, thus could be used as a potential prognostic biomarker of COVID-19.Interpretation Alteration of the URT microbiota was observed in COVID-19 patients and was associated with the fatality rate. A higher abundance of Streptococcus, especially S. parasanguis, on admission in oropharyngeal swabs predicts a better outcome. The generalization of the results in other populations and underlying mechanisms need further investigations.Trial Registration: Participants were enrolled in ChiCTR2000029308.Funding: This study was funded in part by the National Major Science & Technology Project for Control and Prevention of Major Infectious Diseases in China (2017ZX10103004, 2018ZX10301401), the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2019-I2M-2-XX, 2016-I2M-1-014, 2018-I2M-1-003), The Non-profit Central Research Institute Fund of CAMS (2020HY320001, 2019PT310029), Beijing Advanced Innovation Center for Genomics (ICG), and Beijing Advanced Innovation Center for Structural Biology (ICSB).Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study was approved by the Institutional Review Board of Jin Yin-Tan Hospital (KY2020-02.01). Written informed consent was obtained from all patients or their legal representatives if they were too unwell to provide consent.

Dynamics of the upper respiratory tract microbiota and its association with fatality in COVID-19 patients (preprint)

The pandemic of Coronavirus disease 2019 (COVID-19) is ongoing globally, which is a big challenge for public health. Alteration of human microbiota had been observed in COVID-19. However, it is unknown how the microbiota is associated with the fatality in COVID-19. We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 COVID-19 patients recruited in the LOTUS clinical trial (Registration number: ChiCTR2000029308) (including 39 deceased patients), and 95 healthy controls from the same geographic area. The upper respiratory tract (URT) microbiota in COVID-19 patients differed from that in healthy controls, while deceased patients possessed a more distinct microbiota. Streptococcus was enriched in recovered patients, whereas potential pathogens, including Candida and Enterococcus, were more abundant in deceased patients. Moreover, the microbiota dominated by Streptococcus was more stable than that dominated by other species. In contrast, the URT microbiota in deceased patients showed a more significant alteration and became more deviated from the norm after admission. The abundance of Streptococcus on admission, particularly that of S. parasanguinis, was identified as a strong predictor of fatality by Cox and L1 regularized logistic regression analysis, thus could be used as a potential prognostic biomarker of COVID-19. The generalization of the results in other populations and underlying mechanisms needs further investigations.

Study on β-Chitosan against the binding of SARS-CoV-2S-RBD/ACE2 (preprint)

It has been known that SARS-CoV-2 which is considered similar to SARS-CoV invades human respiratory epithelial cells through interaction with the human angiotensin converting enzyme II (ACE2). In this work, SARS-CoV-2S-RBD and its cell receptor ACE2 were used to investigate the blocking effect and mechanism of {beta}-chitosan to the binding of them. Besides, inhibitory effect of {beta}-chitosan on inflammation induced by SARS-CoV-2S-RBD was also studied. Firstly, Native-PAGE results showed that {beta}-chitosan could bind with ACE2 or SARS-CoV-2S-RBD and the conjugate of {beta}-chitosan and ACE2 could no longer bind with SARS-CoV-2S-RBD. HPLC analyses suggested that was found the conjugate of {beta}-chitosan and SARS-CoV-2S-RBD displayed high binding affinity under the condition of high pressure (40 MPa) compared with that of ACE2 and SARS-CoV-2S-RBD. Furthermore, immunofluorescence detections on Vero E6 cells and hACE2 mice showed that {beta}-chitosan had a significant prevention and treatment effect on SARS-CoV-2S-RBD binding. Meanwhile, SARS-CoV-2S-RBD binding could activate the inflammation signaling pathways of cells and mice, however, {beta}-chitosan could dramatically suppress the inflammations activated by SARS-CoV-2S-RBD. Subsequently, Western blot analyses revealed that the expression levels of ACE2 in experimental groups treated with {beta}-chitosan significantly reduced. However, after the intervention of ADAM17 inhibitor (TAPI), the decreased ACE2 expressions affected by {beta}-chitosan up-regulated correspondingly. The results indicated that {beta}-chitosan has a similar antibody function, which can neutralize SARS-CoV-2S-RBD and effectively block the binding of SARS-CoV-2S-RBD with ACE2. ADAM17 activated by {beta}-chitosan can enhance the cleavage of ACE2 extracellular domain with a catalytic activity of Ang II degradation, and then the extracellular region was released into the extracellular environment. So, {beta}-chitosan could prevent the binding, internalization and degradation of ACE2 with SARS-CoV-2S-RBD and inhibit the activation of inflammatory signaling pathways at the same time. This work provides a valuable reference for the prevention and control of SARS-CoV-2 by {beta}-chitosan.

Spatial-temporal distribution of coronavirus disease 2019 in Jingzhou City

Objective • To explore the spatial distribution and spatial-temporal clustering of coronavirus disease 2019(COVID-19) in Jingzhou City. Methods • Data of COVID-19 cases in Jingzhou City from January 1 to March 12, 2020 were collected. Trend surface analysis, spatial autocorrelation and spatial-temporal scanning analysis were conducted to understand the spatial-temporal distribution of COVID-19 at town (street) level in Jingzhou City, and the spatial-temporal clustering characteristics of local cases and imported cases were compared. Results • Trend surface analysis showed that the incidence rate of COVID-19 in Jingzhou City was slightly "U" from west to east, slightly higher in the east, and inverted "U" from south to north, slightly higher in the south. Global autocorrelation showed that the incidence rate of COVID-19 in Jingzhou City was positively correlated (Moran's I=0.410, P=0.000). Local spatial autocorrelation analysis showed that the highly clustered areas and hot spot areas were mainly in Shashi District, Jingzhou District and the main urban area of Honghu City (Xindi Street) (P<0.05). Five clusters were found by spatial-temporal scanning of imported cases. The cluster time of the main cluster was from January 18 to February 3, 2020, and it was centered on Lianhe Street, covering 15 towns (streets) in Shashi District and Jingzhou District (LLR=174.944, RR=7.395, P=0.000). Five clusters were found by spatial-temporal scanning of local cases. The cluster time of the main cluster was from January 20 to February 24, 2020, which was located in Xindi Street, Honghu City (LLR=224.434, RR=16.133, P=0.000). Conclusion • Obvious spatialtemporal clustering of COVID-19 was found in Jingzhou City, and Shashi District, Jingzhou District and Honghu City were the most prevalent areas.

Management strategy of Corona Virus Disease-2019 in quarantine zones outside hospitals: Analysis of 1232 cases from a district in Wuhan (preprint)

The Corona Virus Disease 2019 (COVID-19) has evolved into a global pandemic in the early 2020. Management strategy outside hospitals of the suspected cases, close contacts and discharged patients might be as important as treatment in hospital. We analyzed information from 1232 cases at 14 hotels (requisitioned as quarantine zones) in Qiaokou district, Wuhan during Feb 8th to Mar 4th 2020. Abide by the unquarantine and hospitalization standard, 603 (48.94%) cases were released from quarantine zones; 540 (43.83%) cases were sent to hospital for further medical care. 89 (7.22%) cases remained on quarantine up to the end of the analysis. The reasons for cases sent to the hospital for treatment were either positive for COVID-19 nucleic acid test, progression in pulmonary CT scan, or aggravation of symptoms. 11/59 patients switched from negative to positive for nucleic acid test during stayed in quarantine zones after being discharged from the hospitals. In total, hospitalization and positive rate for COVID-19 nucleic acid test both decreased over time. The quarantine measures were important and played a pivotal role in identification of cardinal number, cutting off the transmission, reducing the scope of prevention and rehabilitation therapy. This protocol adopted in Wuhan provided countries worldwide with valuable experience.

Antibody responses to SARS-CoV-2 in COVID-19 patients: the perspective application of serological tests in clinical practice (preprint)

Background We aim to investigate the profile of acute antibody response in COVID-19 patients, and provide proposals for the usage of antibody test in clinical practice. Methods A multi-center cross-section study (285 patients) and a single-center follow-up study (63 patients) were performed to investigate the feature of acute antibody response to SARS-CoV-2. A cohort of 52 COVID-19 suspects and 64 close contacts were enrolled to evaluate the potentiality of the antibody test. Results The positive rate for IgG reached 100% around 20 days after symptoms onset. The median day of serocon-version for both lgG and IgM was 13 days after symptoms onset. Seroconversion of IgM occurred at the same time, or earlier, or later than that of IgG. IgG levels in 100% patients (19/19) entered a platform within 6 days after seroconversion. The criteria of IgG seroconversion and [≥] 4-fold increase in the IgG titers in sequential samples together diagnosed 82.9% (34/41) of the patients. Antibody test aided to confirm 4 patients with COVID-19 from 52 suspects who failed to be confirmed by RT-PCR and 7 patients from 148 close contacts with negative RT-PCR. Conclusion IgM and IgG should be detected simultaneously at the early phase of infection. The serological diagnosis criterion of seroconversion or [≥] 4-fold increase in the IgG titer is suitable for a majority of COVID-19 patients. Serologic test is helpful for the diagnosis of SARS-CoV-2 infection in suspects and close contacts.