Deep spatial proteomic exploration of severe COVID-19-related pulmonary injury in post-mortem specimens (preprint)

The lung, as a primary target of SARS-CoV-2, exhibits heterogeneous microenvironment accompanied by various histopathological changes following virus infection. However, comprehensive insight into the protein basis of COVID-19-related pulmonary injury with spatial resolution is currently deficient. Here, we generated a region-resolved quantitative proteomic atlas of seven major pathological structures within the lungs of COVID-19 victims by integrating histological examination, laser microdissection, and ultrasensitive proteomic technologies. Over 10,000 proteins were quantified across 71 dissected FFPE post-mortem specimens. By comparison with control samples, we identified a spectrum of COVID-19-induced protein and pathway dysregulations in alveolar epithelium, bronchial epithelium, and pulmonary blood vessels, providing evidence for the proliferation of transitional-state pneumocytes. Additionally, we profiled the region-specific proteomes of hallmark COVID-19 pulmonary injuries, including bronchiole mucus plug, pulmonary fibrosis, airspace inflammation, and hyperplastic alveolar type 2 cells. Bioinformatic analysis revealed the enrichment of cell-type and functional markers in these regions (e.g. enriched TGFBI in fibrotic region). Furthermore, we identified the up-regulation of proteins associated with viral entry, host restriction, and inflammatory response in COVID-19 lungs, such as FURIN and HGF. Collectively, this study provides spatial proteomic insights for understanding COVID-19-caused pulmonary injury, and may serve as a valuable reference for improving therapeutic intervention for severe pneumonia.

Research progress on circular RNA vaccines

Owing to the success of linear mRNA coronavirus disease 2019 (COVID-19) vaccines, biopharmaceutical companies and research teams worldwide have attempted to develop more stable circular RNA (circRNA) vaccines and have achieved some preliminary results. This review aims to summarize key findings and important progress made in circRNA research, the in vivo metabolism and biological functions of circRNAs, and research progress and production process of circRNA vaccines. Further, considerations regarding the quality control of circRNA vaccines are highlighted herein, and the main challenges and problem-solving strategies in circRNA vaccine development and quality control are outlined to provide a reference for circRNA vaccine-related research.

Knowledge mapping of COVID-19 and dentistry: A bibliometric analysis

Background COVID-19 has a significant impact on dental medicine. The present study aims to overview dental-related research on COVID-19 by visual mapping method. Methods We analyzed the publications in the "Dentistry Oral Surgery Medicine” category in the Web of Science core collection. On June 10, 2022, we conducted an advanced search using the items TS = ("Novel coronavirus 2019” or "COVID 19” or "Coronavirus disease 2019” or "2019-nCOV” or "SARS-CoV-2” or "coronavirus-2”) and WC = ("Dentistry Oral Surgery medicine”) to screen publications in the dental field that focus on COVID-19 or SARS-CoV-2. The contributions of authors, journals, institutions, and countries were described using Microsoft Excel 2010 and VOSviewer. The keywords co-occurring analysis and references analysis were visualized using VOSviewer and CiteSpace. Results A total of 1,732 papers were identified between 2020 and 2022. The United States, the United Kingdom, and Brazil were three major contributors to this field. Univ São Paulo (Brazil) ranked first with 55 publications in this field. Martelli Junior, Hercilio from Universidade Jose do Rosario Vellano (Brazil) was the most prolific author with 19 publications. Oral Diseases and British Dental Journal were the two most productive journals. The central topics were dental practice and infection control, oral manifestation related to COVID-19, dental education and online learning, teledentistry, and mental health problems. Conclusion The growth rate of publications regarding dental research on COVID-19 has risen sharply. Research topics shifted from "Dental practice and infection control, oral manifestation related to COVID-19” in 2020 to "Dental education and online learning, teledentistry, mental health problems,” which are three important research topics for the future.

A Reflection on the Response to Sudden-Onset Disasters in the Post-Pandemic Era: A Graded Assessment of Urban Transportation Resilience Taking Wuhan, China as an Example

The COVID-19 pandemic has led to thinking about the response to sudden-onset disasters, for which the transportation resilience of urban areas is crucial. The purpose of paper is to provide a graded assessment of urban transportation resilience to help city managers target policies and plans. Wuhan, the first city in China to be severely hit by COVID-19, was selected as the case study for this research. Based on an extensive survey of the travel characteristics of residents in central urban areas, the concept of 'travel mode shift';was combined to classify residents into four modes, including non-motorized conventional travel, non-motorized over-distance travel, motorized adaptable travel and motorized non-substitutable travel. The potential transportation stoppages in different levels of epidemic impact were then divided into three scenarios, corresponding to each of the city's three levels of transportation resilience. The concept of MWD (Maximum Willingness Distance) in active travel mode was further developed, which was divided into WMWD (Walking Maximum Willingness Distance) and RMWD (Riding Maximum Willingness Distance). Finally, a hierarchical assessment model of urban transportation resilience is developed based on the MWD distance threshold. Besides, the average income level of urban residents was also included in the assessment system. The following research conclusions were drawn: (1) The degree of transportation resilience in Wuhan showed an 'S-curve';relationship with RMWD, with thresholds at RMWD = 2.5 km, 11 km and 23 km respectively. (2) The resilience of transportation in the suburbs of the city was weaker than in the city center, and the gap between the two increases as the RMWD increases, but the share of motorized transportation in short distance trips in the city center was still higher than desirable. (3) The upper-income groups in the city had more flexible travel options, while the lower income groups were less resilient to travel. Based on the results of the study, it is recommended that city managers can identify areas of low resilience and critical distance thresholds that may lead to sudden changes in transportation resilience in the event of a sudden disaster. This will lead to the development of improved policies. The special needs of socially disadvantaged groups should also be taken more into account in this process.

Taking control of violence against doctors

Violence against healthcare professionals is a serious but understudied global problem and one that lacks evidence-based solutions. The current research offers a novel explanation and intervention for addressing this issue: We propose that low feelings of control among patients and their family members play an important role in shaping doctor-patient relationships. To regain a sense of control, we suggest that patients attribute responsibility to doctors for their suffering, which may in turn lead to aggressive behavioural intentions against one's doctors. We conducted three studies to understand whether individuals with low perceived control blame doctors more, and whether threats to their sense of control cause participants to attribute more responsibility to doctors. Study 1 found that feelings of lack of control were an important predictor of attributing responsibility for negative illness-related incidents to doctors in a manner consistent with blame. Study 2 specified that the chaotic and unpredictable nature of illness, and not just its negative valence, is what drives attributions of increased responsibility to doctors. Study 3, which utilized a field setting in hospitals, found that an experimental intervention to increase feelings of control decreased frustration against (Study 3a/3b) and intention to harm doctors (Study 3b). These findings suggest that increasing feelings of control among patients can improve patient-doctor relationships. We also discuss the role of control and scapegoating during the COVID-19 pandemic. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

CRISPR/Cas12a-based SARS-CoV-2 Rapid Visual Detection and Clinical Application (preprint)

Background: Currently, rapid and widespread testing is essential to promote early intervention and curb the ongoing COVID-19 pandemic. The reverse transcription-polymerase chain reaction (RT-PCR) for detecting novel coronavirus (SARS-CoV-2) is restricted to professional laboratories and well-trained personnel, thus, limiting its widespread use in in resource-limited conditions. Methods: To overcome these challenges, we developed a rapid and convenient assay using recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR) technology for the rapid detection SARS-CoV-2, which was named as Visual Detection of RPA-amplified Products (VDAP). The reaction conditions of the VDAP were optimized and selected using pure SARS-CoV-2 RNA standards and the sensitivity and specificity of the VDAP were further determined. Finally, the VDAP was verified on clinical specimens. Results: The VDAP was performed at 37 °C for 15 min, and the result was visible by the naked eye. The limits of detection (LODs) of the VDAP for the target ORF1ab and N genes are 70 and 500 copies, respectively. No cross-reactivity was observed with the RNA standard samples of four respiratory viruses or clinical samples of common respiratory viral infections. These results confirmed that the assay was highly specific. Thirty SARS-CoV-2 positive and 30 SARS-CoV-2 negative patient specimens were analyzed. We compared these results to RT-PCR, the overall sensitivity and specificity of the VDAP compared to RT-PCR for detection SARS-CoV-2 were 93.3% and 100.0%, respectively. Conclusions: The VDAP is a simple, highly specific, and convenient assay for the detection of SARS-CoV-2 in resource-limited conditions

Comparison of Live Birth Rate Among PPOS, GnRH Antagonist and GnRH Agonist in POSEIDON Group 3 (preprint)

Background It is difficult to select an ovarian stimulation protocol for the patients with poor ovarian reserve (POR) because few oocytes are retrieved in a single controlled ovarian stimulation (COS) cycle. The aim of this study was to compare the pregnancy outcomes of different protocols in POSEIDON Group 3 patients.Methods This was a retrospective cohort study. Patients met the POSEIDON Group 3 criteria who underwent assisted reproductive technology at the Reproductive center of Renmin Hospital of Wuhan University between April 2019 and August 2021 were included. The COS protocols included progestin-primed ovarian stimulation (PPOS), GnRH antagonist and GnRH agonist protocols. The live birth rate (LBR) was the primary outcome. The secondary outcome measures were number of oocytes retrieved, duration of gonadotropin (Gn) treatment, amount of Gn administered, fertilization rates, chemical and clinical pregnancy.Results A total of 309 women met the POSEIDON Group 3 criteria were included for analysis. When compared with PPOS group and GnRH antagonist group, anti-Mullerian hormone, antral follicle count and oocytes retrieved were significantly higher in GnRH agonist group (P = 0.021; P < 0.001; P < 0.001); the basal FSH value was significantly lower in GnRH agonist group (P = 0.006); the estradiol values on trigger day and growth hormone utilization rate were significantly increased in GnRH agonist group (P < 0.001; P = 0.001). However, there was no significant difference in the outcomes of embryos, without significant difference in 2 pronuclear rate, transplantable embryo rate and high-quality embryo rate among the three groups. There was also no significant difference in pregnancy outcomes, although the clinical pregnancy rate (61% vs.51.2% vs.44.9%) and LBR (33.3% vs.23.3% vs.23.2%) were higher in GnRH agonist group than PPOS and GnRH antagonist groups, but not statistically significant. The chemical pregnancy rate was significantly higher in GnRH agonist group than GnRH antagonist group (80.5% vs. 56.7%, P = 0.008). LH values on trigger day were significantly higher in GnRH antagonist group than the other two groups (P < 0.001). The cycle cancellation rate and miscarriage rate were highest in PPOS group, but without significant difference.Conclusion For patients with POR diagnosed as POSEIDON Group 3, the LBR is comparable among the PPOS, GnRH antagonist and GnRH agonist protocols. Considering the economic cost and the prevalence of COVID-19, it is recommended to use the short COS regimens with fresh embryo transplantation.

Host Factor Interaction Networks Identified by Integrative Bioinformatics Analysis Reveals Therapeutic Implications in COPD Patients With COVID-19

Background: The COVID-19 pandemic poses an imminent threat to humanity, especially for those who have comorbidities. Evidence of COVID-19 and COPD comorbidities is accumulating. However, data revealing the molecular mechanism of COVID-19 and COPD comorbid diseases is limited. Methods: We got COVID-19/COPD -related genes from different databases by restricted screening conditions (top500), respectively, and then supplemented with COVID-19/COPD-associated genes (FDR<0.05, ;LogFC;≥1) from clinical sample data sets. By taking the intersection, 42 co-morbid host factors for COVID-19 and COPD were finally obtained. On the basis of shared host factors, we conducted a series of bioinformatics analysis, including protein-protein interaction analysis, gene ontology and pathway enrichment analysis, transcription factor-gene interaction network analysis, gene-microRNA co-regulatory network analysis, tissue-specific enrichment analysis and candidate drug prediction. Results: We revealed the comorbidity mechanism of COVID-19 and COPD from the perspective of host factor interaction, obtained the top ten gene and 3 modules with different biological functions. Furthermore, we have obtained the signaling pathways and concluded that dexamethasone, estradiol, progesterone, and nitric oxide shows effective interventions. Conclusion: This study revealed host factor interaction networks for COVID-19 and COPD, which could confirm the potential drugs for treating the comorbidity, ultimately, enhancing the management of the respiratory disease.

A sampling scheme for estimating the prevalence of a pandemic (preprint)

The spread of COVID-19 makes it essential to investigate its prevalence. In such investigation research, as far as we know, the widely-used sampling methods didn't use the information sufficiently about the numbers of the previously diagnosed cases, which provides a priori information about the true numbers of infections. This motivates us to develop a new, two-stage sampling method in this paper, which utilises the information about the distributions of both population and diagnosed cases, to investigate the prevalence more efficiently. The global likelihood sampling, a robust and efficient sampler to draw samples from any probability density function, is used in our sampling strategy, and thus, our new method can automatically adapt to the complicated distributions of population and cases. Moreover, the corresponding estimating method is simple, which facilitates the practical implementation. Some recommendations for practical implementation are given. Finally, several simulations and a practical example verified its efficiency.

The Impact of Chinese College Students' Perceived Stress on Anxiety During the COVID-19 Epidemic: The Mediating Role of Irrational Beliefs.

Objective: To explore the underlying mechanism of the impact of perceived stress on anxiety of the Chinese college students during the COVID-19 epidemic. Methods: The Perceived Stress Scale, Irrational Belief Scale, and General Anxiety Scale were adopted in the current study. College students were randomly selected for online questionnaire survey. There were 1,598 valid questionnaires, and the proportion of women was 47.81%. Results: The perceived stress and anxiety, as well as the three dimensions of irrational beliefs (catastrophizing, low frustration tolerance, and depreciation) were significantly positively correlated; demandingness was not significantly correlated with anxiety. Further analysis found that the perceived stress had a significant positive predictive effect on the anxiety of college students. Catastrophizing, low frustration tolerance, and depreciation played part of the mediating role, and there was no significant difference in the strength of these mediating roles. Conclusion: The perceived stress of the COVID-19 epidemic had a positive effect on the anxiety of Chinese college students, this was partly mediated by irrational beliefs.

Quantifying Air Pollutant Variations during COVID-19 Lockdown in a Capital City in Northwest China

In the context of the outbreak of coronavirus disease 2019 (COVID-19), strict lockdown policies were implemented to control nonessential human activities in Xi’an, northwest China, which greatly limited the spread of the pandemic and affected air quality. Compared with pre-lockdown, the air quality index and concentrations of PM2.5, PM10, SO2, and CO during the lockdown reduced, but the reductions were not very significant. NO2 levels exhibited the largest decrease (52%) during lockdown, owing to the remarkable decreased motor vehicle emissions. The highest K+ and lowest Ca2+ concentrations in PM2.5 samples could be attributed to the increase in household biomass fuel consumption in suburbs and rural areas around Xi’an and the decrease in human physical activities in Xi’an (e.g., human travel, vehicle emissions, construction activities), respectively, during the lockdown period. Secondary chemical reactions in the atmosphere increased in the lockdown period, as evidenced by the increased O3 level (increased by 160%) and OC/EC ratios in PM2.5 (increased by 26%), compared with pre-lockdown levels. The results, based on a natural experiment in this study, can be used as a reference for studying the formation and source of air pollution in Xi’an and provide evidence for establishing future long-term air pollution control policies.

Investigation and Analysis of the Sub-health Status of the Members of the Medical Team Aiding Wuhan During the Novel Coronavirus Pneumonia (COVID-19) Outbreak (preprint)

Objective: To understand the sub-health status of the medical team members of the aid to Wuhan during the outbreak of the new coronavirus pneumonia in Wuhan, China, to analyze the possible influencing factors that cause the sub-health status, and to provide a theoretical basis for scientifically maintaining and improving the physical and mental health of the medical team members.Methods: 131 members of the military medical team aiding Wuhan who were treating patients with novel coronavirus pneumonia were selected as subjects in the survey, and a questionnaire on the sub-health influencing factors was designed. After the medical treatment task, the SHMS V1.0 was used for assessment.Results: The sub-health detection rate of the medical team members was 76.3%, and the overall sub-health rating scale score was (69.11 ± 10.20) points. The scores of the three subscales of physiology, psychology, and society are (71.16 ± 11.30) points, (67.99 ± 13.51) points, and (67.41 ± 12.31) points, respectively. Work pressure, family structure, frustration, and diet may be the influence factors of the sub-health. Conclusion: During the outbreak of the novel coronavirus pneumonia, factors such as high-intensity work, non-nuclear families, low hobbies, and irregular diet may lead to the sub-healthy state of the members of the medical aid team in Wuhan. Reasonable arrangements for work and rest, maintaining harmonious family relations, focusing on the development of interests and hobbies, and healthy and regular diet, will help maintain and improve the health of medical team members, consolidate and maintain the combat effectiveness of medical team members, and complete epidemic prevention and control tasks with high quality and efficiency.

Evaluation of the current therapeutic approaches for COVID-19: a meta-analysis (preprint)

Background and rationale: Limited data on the efficacy and safety of currently applied COVID-19 therapeutics and their impact on COVID-19 outcomes have raised additional concern. Aim and Methods: We estimated the impact of the current treatments on the efficacy and safety of COVID-19 by a meta-analysis. The comprehensive search included studies reporting clinical features and treatment strategies published from January 21, 2020, to May 15, 2020. Results: We included 52 studies that involved 13,966 COVID-19 patients. We found that the most prevalent treatments were antivirals (proportion: 0.74, 95% CI : [0.65, 0.83]) and antibiotics (proportion: 0.73, 95% CI: [0.62, 0.83]). The COVID-19 severity increased among patients taking glucocorticoids (risk ratio (RR) = 1.71, 95% CI: [1.06, 2.76]) or immunoglobulins (RR = 3.83, 95% CI: [1.27, 11.53]), and renal replacement therapy (RRT) and glucocorticoids increased the length of ICU stay (RRT : RR= 11.89, 95% CI: [3.26, 43.39]; glucocorticoids: RR = 3.10, 95% CI: [1.52, 6.29]). The COVID-19 severity and mortality increased among patients taking tocilizumab (severity: F = 25.53, P = 0.02; mortality: F = 19.37, P = 0.02). The most effective treatment was the combination of arbidol with lopinavir/ritonavir compared with placebo (mean difference = 0.5, 95% CI [-0.60, 1.66]), and the safest combination was remdesivir and lopinavir/ritonavir (RR= 0.78, 95% CI [0.32, 1.91]). Conclusion: glucocorticoids, immunoglobulins, RRT, and tocilizumab might worsen COVID-19 outcomes, and the most effective and safest treatment strategy for COVID-19 is the combination of different antivirals.

Identifying novel factors associated with COVID-19 transmission and fatality using the machine learning approach (preprint)

The COVID-19 virus has infected millions of people and resulted in hundreds of thousands of deaths worldwide. By using the logistic regression model, we identified novel critical factors associated with COVID19 cases, death, and case fatality rates in 154 countries and in the 50 U.S. states. Among numerous factors associated with COVID-19 risk, we found that the unitary state system was counter-intuitively positively associated with increased COVID-19 cases and deaths. Blood type B was a protective factor for COVID-19 risk, while blood type A was a risk factor. The prevalence of HIV, influenza and pneumonia, and chronic lower respiratory diseases was associated with reduced COVID-19 risk. Obesity and the condition of unimproved water sources were associated with increased COVID-19 risk. Other factors included temperature, humidity, social distancing, smoking, and vitamin D intake. Our comprehensive identification of the factors affecting COVID-19 transmission and fatality may provide new insights into the COVID-19 pandemic and advise effective strategies for preventing and migrating COVID-19 spread.

Taking the pulse of COVID-19: A spatiotemporal perspective (preprint)

The sudden outbreak of the Coronavirus disease (COVID-19) swept across the world in early 2020, triggering the lockdowns of several billion people across many countries, including China, Spain, India, the U.K., Italy, France, Germany, and most states of the U.S. The transmission of the virus accelerated rapidly with the most confirmed cases in the U.S., and New York City became an epicenter of the pandemic by the end of March. In response to this national and global emergency, the NSF Spatiotemporal Innovation Center brought together a taskforce of international researchers and assembled implemented strategies to rapidly respond to this crisis, for supporting research, saving lives, and protecting the health of global citizens. This perspective paper presents our collective view on the global health emergency and our effort in collecting, analyzing, and sharing relevant data on global policy and government responses, geospatial indicators of the outbreak and evolving forecasts; in developing research capabilities and mitigation measures with global scientists, promoting collaborative research on outbreak dynamics, and reflecting on the dynamic responses from human societies.

Spatiotemporal Patterns of COVID-19 Impact on Human Activities and Environment in China Using Nighttime Light and Air Quality Data (preprint)

In order to analyze the impact of COVID-19 on people's lives, activities and the natural environment, this paper investigates the spatial and temporal characteristics of Night Time Light (NTL) radiance and Air Quality Index (AQI) before and during the pandemic in mainland China. Our results show that the monthly average NTL brightness is much lower during the quarantine period than before. This study categorizes NTL into three classes: residential area, transportation and public facilities and commercial centers, with NTL radiance ranges of 5-20, 20-40 and greater than 40 nW/(cm*cm*sr), respectively. We found that the Number Of Pixels (NOP) with NTL detection increased in the residential area and decreased in the commercial centers for most of the provinces after the shutdown, while transportation and public facilities generally stayed the same. More specifically, we examined these factors in Wuhan, where the first confirmed cases were reported, and where the earliest quarantine measures were taken. Observations and analysis of pixels associated with commercial centers were observed to have lower NTL radiance values, indicating a dimming behavior, while residential area pixels recorded increased levels of brightness, after the beginning of the lockdown. The study also discovered a significant decreasing trend in the daily average AQI for the whole country, with cleaner air in most provinces during February and March, compared to January 2020. In conclusion, the outbreak and spread of COVID-19 has had a crucial impact on people's daily lives and activity ranges through the increased implementation of lockdown and quarantine policies. On the other hand, the air quality of China has improved with the reduction of non-essential industries and motor vehicle usage.

Tocilizumab treatment in severe COVID-19 patients attenuates the inflammatory storm incited by monocyte centric immune interactions revealed by single-cell analysis (preprint)

ABSTRACTDespite the current devastation of the COVID-19 pandemic, several recent studies have suggested that the immunosuppressive drug Tocilizumab can powerfully treating inflammatory responses that occur in this disease. Here, by employing single-cell analysis of the immune cell composition of severe-stage COVID-19 patients and these same patients in post Tocilizumab-treatment remission, we have identified a monocyte subpopulation specific to severe disease that contributes to inflammatory storms in COVID-19 patients. Although Tocilizumab treatment attenuated the strong inflammatory immune response, we found that immune cells including plasma B cells and CD8+ T cells still exhibited an intense humoral and cell-mediated anti-virus immune response in COVID-19 patients after Tocilizumab treatment. Thus, in addition to providing a rich, very high-resolution data resource about the immune cell distribution at multiple stages of the COVID-19 disease, our work both helps explain Tocilizumab’s powerful therapeutic effects and defines a large number of potential new drug targets related to inflammatory storms.Competing Interest StatementJingwen Fang is the executive officer of HanGen BiotechView Full Text

Health Communication Through News Media During the Early Stage of the COVID-19 Outbreak in China: A Digital Topic Modeling Approach (preprint)

Background : In December 2019, some COVID-19 cases were first reported and soon the disease broke out. As this dreadful disease spreads rapidly, the mass media has been active in community education on COVID-19 by delivering health information about this novel coronavirus. | Methods: We adopted the Huike database to extract news articles about coronavirus from major press media, between January 1st, 2020, to February 20th, 2020. The data were sorted and analyzed by Python software and Python package Jieba. We sought a suitable topic number using the coherence number. We operated Latent Dirichlet Allocation (LDA) topic modeling with the suitable topic number and generated corresponding keywords and topic names. We divided these topics into different themes by plotting them into two-dimensional plane via multidimensional scaling. | Findings: After removing duplicates, 7791 relevant news reports were identified. We listed the number of articles published per day. According to the coherence value, we chose 20 as our number of topics and obtained their names and keywords. These topics were categorized into nine primary themes based on the topic visualization figure. The top three popular themes were prevention and control procedures, medical treatment and research, global/local social/economic influences, accounting for 32.6%, 16.6%, 11.8% of the collected reports respectively. | Interpretation: The Chinese mass media news reports lag behind the COVID-19 outbreak development. The major themes accounted for around half the content and tended to focus on the larger society than on individuals. The COVID-19 crisis has become a global issue, and society has also become concerned about donation and support as well as mental health. We recommend that future work should address the mass media's actual impact on readers during the COVID-19 crisis through sentiment analysis of news data.