High myoglobin level as an independent risk factor for death in patients with critical COVID-19 infection：A retrospective case-control study (preprint)

Aim This study aimed to discover risk factors for death in patients with critical COVID-19 infection in order to identify patients with a higher risk of death at an early stage.Methods We retrospectively analyzed the clinical data of patients with critical COVID-19 infection from April 2022 to June 2022. Data were collected from the electronic medical records. Propensity matching scores were used to reduce the effect of confounding factors, such as patient baseline variables. Independent risk factors affecting patient prognosis were assessed using univariate logistic regression and multivariate logistic regression analysis. Restricted cubic spline curves were used to assess the relationship between independent and dependent variables.Results The data of 137 patients with critical COVID-19 infection were collected. Of the 137 patients, 84 survived and 53 died. Among laboratory indicators, patients who died had higher proportions of abnormalities in RDW SD, procalcitonin, aspartate aminotransferase (AST), creatinine, potassium, cardiac troponin I, and myoglobin. Univariate and multivariate logistic regression analyses suggested that abnormal AST (OR = 3.26, P = 0.044), creatinine (OR = 4.49, P = 0.037), and myoglobin (OR = 9.88, P = 0.025) were independent risk factors for death. After correction for AST and creatinine, a linear relationship between myoglobin and risk of death in patients was found using restricted cubic splines.Conclusion High myoglobin level is an independent risk factor for death and is therefore a prognostic marker in patients with severe COVID-19 infection.

A Novel COVID-19 Image Classification Method Based on the Improved Residual Network

In recent years, chest X-ray (CXR) imaging has become one of the significant tools to assist in the diagnosis and treatment of novel coronavirus pneumonia. However, CXR images have complex-shaped and changing lesion areas, which makes it difficult to identify novel coronavirus pneumonia from the images. To address this problem, a new deep learning network model (BoT-ViTNet) for automatic classification is designed in this study, which is constructed on the basis of ResNet50. First, we introduce multi-headed self-attention (MSA) to the last Bottleneck block of the first three stages in the ResNet50 to enhance the ability to model global information. Then, to further enhance the feature expression performance and the correlation between features, the TRT-ViT blocks, consisting of Transformer and Bottleneck, are used in the final stage of ResNet50, which improves the recognition of complex lesion regions in CXR images. Finally, the extracted features are delivered to the global average pooling layer for global spatial information integration in a concatenated way and used for classification. Experiments conducted on the COVID-19 Radiography database show that the classification accuracy, precision, sensitivity, specificity, and F1-score of the BoT-ViTNet model is 98.91%, 97.80%, 98.76%, 99.13%, and 98.27%, respectively, which outperforms other classification models. The experimental results show that our model can classify CXR images better.

Impact of the COVID-19 pandemic on cardiac implantable electronic device implantation in China: Insights from 2 years of changing pandemic conditions

Background A substantial reduction in the number of cardiac implantable electronic device (CIED) implantation was reported in the early stages of the COVID-19 pandemic. None of the studies have yet explored changes in CIED implantation during the following pandemic. Objective To explore changes in CIED implantation during the COVID-19 pandemic from 2020 to 2021. Methods From 2019 to 2021, 177,263 patients undergone CIED implantation from 1,227 hospitals in China were included in the analysis. Generalized linear models measured the differences in CIED implantation in different periods. The relationship between changes in CIED implantation and COVID-19 cases was assessed by simple linear regression models. Results Compared with the pre-COVID-19 period, the monthly CIED implantation decreased by 17.67% (95% CI: 16.62–18.72%, p < 0.001) in 2020. In 2021, the monthly number of CIED implantation increased by 15.60% (95% CI: 14.34–16.85%, p < 0.001) compared with 2020. For every 10-fold increase in the number of COVID-19 cases, the monthly number of pacemaker implantation decreased by 429 in 2021, while it decreased by 676 in 2020. The proportion of CIED implantation in secondary medical centers increased from 52.84% in 2019 to 56.77% in 2021 (p < 0.001). For every 10-fold increase in regional accumulated COVID-19 cases, the proportion of CIED implantation in secondary centers increased by 6.43% (95% CI: 0.47–12.39%, p = 0.036). Conclusion The impact of the COVID-19 pandemic on the number of CIED implantation is diminishing in China. Improving the ability of secondary medical centers to undertake more operations may be a critical way to relieve the strain on healthcare resources during the epidemic.

General Short-Term Load Forecasting Based on Multi-Task Temporal Convolutional Network in COVID-19

The spread of the global COVID-19 epidemic has resulted in significant shifts in electricity consumption compared to regular days. It is unknown if standard single-task, single-indicator load forecasting algorithms can accurately reflect COVID-19 load patterns. Power practitioners urgently want a simple, efficient, and accurate solution for anticipating reliable load. In this paper, we first propose a unique collaborative TCN-LSTM-MTL short-term load forecasting model based on mobility data, temporal convolutional networks, and multi-task learning. The addition of the parameter sharing layers and the structure with residual convolution improves the data input diversity of the forecasting model and enables the model to obtain a wider time series receptive field. Then, to demonstrate the usefulness of the mobility optimized TCN-LSTM-MTL, tests were conducted in three levels and twelve base regions using 19 different benchmark models. It is capable of controlling predicting mistakes to within 1% in the majority of tasks. Finally, to rigorously explain the model, the Shapley additive explanations (SHAP) visual model interpretation technology based on game theory is introduced. It examines the TCN-LSTM-MTL model's internal mechanism at various time periods and establishes the validity of the mobility indicators as well as the asynchronous relationship between indicator significance and real contribution.

Understanding Bike-sharing Mobility Patterns in Response to the COVID-19 Pandemic (preprint)

The outbreak of COVID-19 brings huge challenges to the bike-sharing system and even society structure. Thus, it is urgent to fully understand the impacts of pandemic on bike-sharing behavior. This paper proposed a comprehensive approach to investigate the mobility patterns influenced by the outbreak of COVID-19 pandemic with the case in Washington D.C. Multiple-source data, including bike-sharing trip information, COVID-19 information, geographic and POI information, were collected. Although the total bike-sharing trips decreased up to 80% in spatial-temporal analysis, the trips made by casual user still increased. In addition, the docking stations and trips from 2019 to 2021 were utilized to construct the bike-sharing network. The results present that major network properties, such as connectivity, clustering coefficient, and accessibility, experienced significant decrease during the pandemic. Through the detection of community with modularity method, the evolution of community structure before and after pandemic was captured. The increased long-range and long-time bike-sharing trips results in the combination between central communities and outer communities. To better understand the community structure, the POI (Point of Interests) auxiliary analysis was conducted and central community was found to have similar proportion of POIs even during the pandemic. Implications for bike-sharing management and operation policy was also addressed.

Infectiousness of places – Impact of multiscale human activity places in the transmission of COVID-19

COVID-19 raises attention to epidemic transmission in various places. This study analyzes the transmission risks associated with human activity places at multiple scales, including different types of settlements and eleven types of specific establishments (restaurants, bars, etc.), using COVID-19 data in 906 urban areas across four continents. Through a difference-in-difference approach, we identify the causal effects of activities at various places on epidemic transmission. We find that at the micro-scale, though the transmission risks at different establishments differ across countries, sports, entertainment, and catering establishments are generally more infectious. At the macro-scale, contradicting common beliefs, it is consistent across countries that transmission does not increase with settlement size and density. It is also consistent that specific establishments play a lesser role in transmission in larger settlements, suggesting more transmission happening elsewhere. These findings contribute to building a system of knowledge on the linkage between places, human activities, and disease transmission.

Investigation of a cluster of COVID-19 cases imported through inbound air flight

Objective: To understand the epidemiological characteristics and explore source of infection of coronavirus disease 2019 (COVID-19) cases imported through an inbound air flight from Kenya to Guangzhou, China.

Exploring psychological resilience of entrepreneurial college students for post-pandemic pedagogy: The mediating role of self-efficacy

The psychological impact of the COVID-19 epidemic on college students is an important topic. With the entry of the post-epidemic era, how universities can better improve students’ psychological resilience in teaching is the research topic of this article. In the form of a questionnaire survey, some entrepreneurial college students investigated the loneliness and psychological resilience of college students after the outbreak of the epidemic and explored the role of self-efficacy in it. The data is collected online through cooperation with an entrepreneurial event, and the participating students are asked for background information such as colleges, grade, and majors. After collecting this information, they answered a series of simplified scale questions about loneliness, self-efficacy, and psychological resilience. In the end, a total of 200 questionnaires from different universities were collected, and the structural equation model was used to explore the role of self-efficacy. The results show that: loneliness has a significant negative effect on Self-efficacy, β = -0.292, p < 0.001;Self-efficacy has a significant positive effect on psychological resilience, β = 0.556, p < 0.0 01;loneliness has a significant negative effect on psychological resilience, β = -0.244, p < 0.01. Self-Efficacy has a significant intermediate effect in loneliness and psychological resilience, with an effective value of -0.111 and p < 0.01. The results show that this exploratory survey finds it important to provide targeted personal self-efficacy improvement activities for college students with a strong sense of loneliness and to combine school and family education organically to help college students form a healthy and upward mentality to better cope with the unknown and troubles caused by the epidemic, which will help improve the psychological resilience of college students in the epidemic.

Analysis of the proliferation characteristics of porcine deltacoronavirus on suspension cultured porcine kidney cell LLC-PK1

This study aimed to analyze the proliferation characteristics of porcine deltacoronavirus (PDCoV) in suspension cultured porcine kidney cells LLC-PK1, so as to provide Candidate cell for large-scale production of PDCoV inactivated vaccine. LLC-PK1 cells were suspended by gradually decreasing serum method. PDCoV adaptive monoclonal cell lines were screened by limited dilution method. Indirect immunofluorescence method was used to identify the infectivity of PDCoV. The initial cell density, MOI, time of receiving virus collection and TPCK pancreatin concentration were screened to determine the best suspension culture conditions. The suspension cell strain LLC-PK1Sa which can proliferate PDCoV efficiently was screened out;PDCoV can specifically infect LLC-PK1 cells;PDCoV inoculated LLC-PK1Sa cells with a density of 2 x 106 cells.mL-1 according to the MOI of 10-3, When the final concentration of TPCK pancreatin reached 7.5 g.mL-1, the titer of virus solution harvested 48 h after inoculation was the highest. In this study, the efficient proliferation of PDCoV in LLC-PK1Sa suspension cells was realized for the first time, and the suspension culture conditions were preliminarily optimized, which could provide theoretical reference for large-scale production of PDCoV inactivated vaccine.

Shedding of SARS-CoV-2 for 85 Days in COVID-19 Patients With Type 2 Diabetes Mellitus and Lung Metastasis: A Case Report

Background COVID-19 (coronavirus disease 2019) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seriously endangers people's lives. The variation in SARS-CoV-2 makes the research and development of vaccines and specific drugs particularly important. However, the prevention and diagnosis of COVID-19 cannot be underestimated in the control of the epidemic. Case Presentation We introduced a 65-year-old female patient who was diagnosed with COVID-19. The SARS-CoV-2 nucleic acid test result of this patient was positive again during treatment. It took 85 days from the first symptom to the final cure. According to the known reports, she is currently the patient with the longest virus shedding in Sichuan Province, China. Due to the patient's special condition, she was treated in four hospitals before and after, and she was diagnosed with type 2 diabetes mellitus (T2DM) and right lung metastatic adenocarcinoma. We fully introduced the patient's epidemiological history, diagnosis, testing, and treatment process. The patient was finally discharged from the hospital under the treatment of antiviral, hypoglycaemic, anti-anxiety, and a combination of Chinese and Western medicine. Conclusions The epidemic is still rampant, and we should not relax our efforts in the prevention and control of viruses. For the elderly, especially those who are suffering from complications or vulnerable to diseases, it is recommended to extend the observation time. Additionally, medical workers should pay attention to the mental state of patients.

Clinical and Virological Features of the First Occurrence of COVID-19 Delta Variant in Anhui Province, China (preprint)

Objectives Since the outbreak of coronavirus disease 2019 (COVID-19), it has caused serious casualties worldwide. In recent months, the virus has mutated into an increasingly infectious form (Delta variant) and spread rapidly.Methods In the current study, we analyzed the clinical, epidemiological and viral genetic characteristics of the first four imported Delta cases in Anhui Province, China.Results The four imported Delta cases developed chest inflammation, tissue damage and recovered after admission, the serum high-sensitivity C-reactive protein (hs-CRP) and CRP levels showed a first increasing and then decreasing trend. The changes of hs-CRP /CRP and serum neutralizing antibodies (Nab) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels were associated with the regression of chest lesions. The combination of genetic sequencing and epidemiological analysis suggested that the SARS-CoV-2 delta variant infection of these four patients may originate from Russia.Conclusions Our study found the certain correlations of serum hs-CRP/CRP and Nab levels with the occurrence, development and outcome of COVID-19 delta variant, suggesting that monitoring hs-CRP/CRP and Nab levels of COVID-19 delta variant patients at hospital admission may be useful for understanding the severity of patients’ current conditions.

Four doses of the inactivated SARS-CoV-2 vaccine redistribute humoral immune responses away from the Receptor Binding Domain (preprint)

A recent MMWR reported that the effectiveness of a 3rd dose of SARS-CoV-2 mRNA vaccine waned quickly in the Omicron-predominant period. Similarly, a substantial decline of immune responses induced by a 3rd dose of inactivated vaccines was also observed in our study. In response to the fast waning immune response and the great threat of Omicron variant of concern (VOC) to frontline healthcare workers (HCWs), 38 HCWs who were in our previous cohort investigating responses to the first three doses of inactivated vaccines participated in the current study and volunteered to receive a 4th homologous booster. Here, we demonstrated that the 4th dose is safe and capable of recalling waned immune responses 6 months after the 3rd dose. However, a greater suppression on the induction of overall Neutralizing antibodies (NAbs) and NAbs targeting the receptor-binding domain (RBD) was found in participants with stronger immune responses after the 3rd dose. As a result, a stepwise elevation of RBD-NAbs from the 1st to the 3rd vaccination achieved a "turning point". The peak RBD-NAbs level induced by the 4th dose was inferior to the peak of the 3rd dose. Accompanied with reduced induction of RBD-NAbs, the immune system shifted responses to the nucleocapsid protein (NP) and the N-terminal domain (NTD) of the spike protein. Although NTD directed antibodies are capable of neutralization, they only compensated the loss of RBD-NAbs to ancestral SARS-CoV-2 virus but not to the Omicron variant due to a substantial conformational change of Omicron NTD. This longitudinal clinical study monitored the immune response of the same cohort for every doses, shaping a relationship between the trajectory of immune focus and the dynamics of the neutralizing potency against the evolving virus. Our data reveal that immune responses could not be endlessly elevated, while suppression of heightened immune responses focusing on one subunit together with a shift of immune responses to other subunits would occur after repeated vaccination. Thus, an updated vaccine with more diverse epitopes capable of inducing NAbs against VOCs would be a future direction for boosters.

The Impact of Online Teaching Under the COVID-19 Pandemic on the Teaching of Medical Immunology and Medical Microbiology to Second-Year Dentistry Students: A Prospective Comparative Study (preprint)

Background Medical microbiology and medical immunology are required introductory courses for second-year dentistry students. It is essential to find suitable teaching methods after the outbreak of COVID-19 to implement the call for "stop class, but not stop teaching and not stop learning."Methods We mainly used Rain Classroom for online teaching and QQ Group Classroom to support education during this particular period.Result We assessed the effectiveness of this special period instruction by analyzing anonymous questionnaires and final exam results. The anonymous questionnaire showed that most of the students were satisfied with this online instruction and found it very helpful in answering their questions and solving their problems. The final exam results showed that teaching in 2020 was no worse than teaching in 2019 and better in terms of pass rate. Teaching in 2021 was worse than in 2020, but there was a breakthrough in the highest score.Conclusion These data suggest that online teaching during the epidemic had an impact on teaching effectiveness. Most students are satisfied with online teaching, but some students' grades are affected, which may be related to the fact that some students were not comfortable with blended teaching or online teaching. We share our experiences and reflections on online and blended teaching of medical immunology and medical microbiology courses during the epidemic, hoping that it will be helpful for other teachers to teach.

Comparative miRNA Transcriptomics of Mouse and Macaque Reveals MYOC is An Inhibitor for C. neoformans Invasion into Brain (preprint)

Cryptococcal meningoencephalitis is an emerging infection shifted from primarily ART-naive to being ART-experienced HIV/AIDS patients, COVID-19 patients and also in immune competent individuals, mainly caused by the human opportunistic pathogen Cryptococcus neoformans , yet mechanisms of the brain or CNS dissemination remain to elucidate, which is the deadest process for the disease. Meanwhile, illustrations of clinically relevant responses in cryptococcosis were limited, as the low availabilities of clinical samples. In this study, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton, a major feather in HIV/AIDS patients, was a centric pathway regulated in both two infection models. Notably, assays of clinical immune cells confirmed an enhanced “Trojan Horse” in HIV/AIDS patients, which can be shut down by cytoskeleton inhibitors. Furthermore, we identified a novel enhancer for macrophage “Trojan Horse”, myocilin, and an enhanced fungal burden was achieved in brains of MYOC transgenic mice. Taking together, this study reveals fundamental roles of cytoskeleton and MYOC in blocking fungal CNS dissemination, which not only helps to understand the high prevalence of cryptococcal meningitis in HIV/AIDS, but also facilitates the development of novel drugs for therapies of meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.

A human monoclonal antibody potently pan-neutralizes SARS-CoV-2 VOCs by targeting RBD invariant sites (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.