Diversity and independent evolutionary profiling of rodent-borne pathogens in tropical island, China (preprint)

The risk of emerging infectious diseases (EID) is increasing globally. More than 60% of EIDs worldwide are caused by animal-borne pathogens, and most viral pathogens are rodent-borne. This study aimed to characterise the virome and analyse the phylogenetic evolution and diversity of rodent-borne viruses in Hainan Province, China. We collected 588 anal and throat samples from rodents, combined them into 28 pools according to their species and location, and processed them for next-generation sequencing and bioinformatics analysis. The diverse viral reads closely related to mammals were assigned to 15 viral families. Molecular clues of the important rodent-borne viruses were further identified by polymerase chain reaction for phylogenetic analysis and annotation of genetic characteristics such as coronavirus, arenavirus, picornavirus. We identified a pestivirus in Leopoldoms edwardsi and two bocaviruses in Rattus andamanensis and Leopoldoms edwardsi from the national nature reserves of Jianfengling and Bangxi with low amino acid identity to known pathogens are proposed as the novel species, and their rodent hosts have not been previously reported to carry these viruses. These results expand our knowledge of viral classification and host range and suggest that there are highly diverse, undiscovered viruses that have evolved independently in their unique wildlife hosts in inaccessible areas, which may cause zoonosis if they cross their host barrier. Our virome and phylogenetic analyses of rodent-borne viruses provide basic data for the prevention and control of human infectious diseases caused by rodent-borne viruses in the subtropical area of China.

A Telecommuting Experience Service Design Decision Model Based on BP Neural Network

Introduction The telecommuting experience and job performance have been significantly impacted by the COVID-19 pandemic, and job performance stability of telecommuting employees has become a critical concern. Objective A decision model for telecommuting experience service design was constructed based on a backpropagation (BP) neural network to provide a theoretical basis for enterprises to evaluate telework performance and the psychological health of employees. Methods The analytic hierarchy process (AHP) was used to determine the core stakeholders. The grey relational analysis (GRA) method and the NASA Task Load Index (NASA-TLX) scale were used to measure the factors affecting employees’ telecommuting experience and job performance. A BP neural network relationship model of employees’ telecommuting experience was established to predict its impact on employees’ job performance. Results Based on the model prediction results, a service system map was created, and the potential to enhance the telework performance of employees was evaluated. Discussion It was concluded that the factors affecting the telecommuting experience were diverse, but emotions had the dominant influence. Significant positive correlations were found between emotional impact and temporal perception, execution difficulty, and communication barriers. Conclusion The proposed decision model for telecommuting experience service design accurately predicted the impact of telecommuting efficiency, providing an effective approach for innovative remote management.

Online Education and Undergraduates' Academic Record during the COVID-19 Pandemic in China: Evidence from Large-Scale Data

Digital technology-based online education is key to promoting high-quality development of higher education. Many studies have analyzed the effects of online education during the COVID-19 pandemic, but analyses based on large-scale data are lacking. This study uses a quasi-natural experiment during the COVID-19 pandemic to explore the short- and long-term relationships between emergency remote education (teaching and learning) and undergraduates' academic record using multiple comparison analysis of variance (ANOVA) and multiple linear regression. The research data come from the academic record of 123,208 courses of 2622 undergraduates from the classes of 2017–2021 in a Chinese university, across nine semesters. The data do not satisfy the homogeneity of variance hypothesis test;therefore, a non-parametric test is adopted for hypothesis testing. The results show that: (1) In the online education semester, the students' academic record improved substantially with low fluctuation and greater stability;(2) this improvement is more obvious for sophomores and juniors than for freshmen, and (3) online education during the pandemic period significantly improved the course scores of undergraduates, especially sophomores, in the following one or two semesters.

Interleukin-18-primed human umbilical cord-mesenchymal stem cells achieve superior therapeutic efficacy for severe viral pneumonia via enhancing T-cell immunosuppression (preprint)

Coronavirus disease 2019 (COVID-19) treatments are still urgently needed for critically and severely ill patients. Human umbilical cord-mesenchymal stem cells (hUC-MSCs) infusion has therapeutic benefits in COVID-19 patients; however, uncertain therapeutic efficacy has been reported in severe patients. In this study, we selected an appropriate cytokine, IL-18, based on the special cytokine expression profile in severe pneumonia of mice induced by H1N1virus to prime hUC-MSCs in vitro and improve the therapeutic effect of hUC-MSCs in vivo. In vitro, we demonstrated that IL-18-primed hUC-MSCs (IL18-hUCMSC) have higher proliferative ability than non-primed hUC-MSCs (hUCMSCcon), and there was no significant difference in their migration capacity. In addition, VCAM-1, MMP-1, TGF-β1, and some chemokines (CCL2 and CXCL12, for example) are more highly expressed in IL18-hUCMSCs. We found that IL18-hUCMSC significantly enhanced the immunosuppressive effect on CD3+ T-cells. In vivo, we demonstrated that IL18-hUCMSC infusion could reduce the body weight loss caused by a viral infection and significantly improve the survival rate. Of note, IL18-hUCMSC can also significantly attenuate certain clinical symptoms, including reduced activity, ruffled fur, hunched backs, and lung injuries. Pathologically, IL18-hUCMSC transplantation significantly enhanced the inhibition of inflammation, viral load, fibrosis, and cell apoptosis in acute lung injuries. Notably, IL18-hUCMSC treatment has a superior inhibitory effect on T-cell exudation and proinflammatory cytokine secretion in bronchoalveolar lavage fluid (BALF). Altogether, IL-18 is a promising cytokine that can prime hUC-MSCs to improve the efficacy of precision therapy against viral-induced pneumonia, such as COVID-19.

Establishment and application of triple PCR method for FAstV, FPV and FECoV

Feline Astrovirus (FAstV), Feline Parvovirus(FPV) and Feline Enteric Coronavirus (FECoV) are important pathogens causing diarrhea in cats.In order to establish a molecular detection method which can differentiate the three pathogens in the same PCR system, an FAstV/FPV/FECoV triple PCR method was established with optimized primer concentrations and annealing temperature, and specificity, sensitivity and repeatability were tested. The results showed that the PCR method could only identify FAstV (320 bp), FPV (468 bp) and FECoV (664 bp) genes, while not other canine and feline related pathogens. The detection limits of FAstV, FPV and FECoV were 2x10~7 copy/L (7.1 pg/L),4.7x10~6 copy/L (2.4 pg/L) and 7x10~6 copy/L (5.1 pg/L) respectively. The established triple PCR method was used to detect 207 cat fecal samples collected in Chengdu from 2019 to 2020, including 141 diarrhea samples and 66 clinical health samples. The detection rates of FAstV, FPV and FECoV were 24.15% (50/207), 37.20% (77/207) and 15.46% (32/207) respectively, and the co-infection rates of FAstV/FPV, FPV/FECoV and FAstv/FECoV were 9.18%,6.28% and 6.28% respectively. In conclusion, the triple PCR method of FAstV/FPV/FECoV was successfully established, and could be applied for virus detection and epidemiological investigation.

Video conferencing software selection based on hybrid MCDM and cumulative prospect theory under a major epidemic

The video conferencing software is regarded as a significant tool for social distancing and getting incorporations up and going. Due to the indeterminacy of epidemic evolution and the multiple criteria, this paper proposes a video conferencing software selection method based on hybrid multi-criteria decision making (HMCDM) under risk and cumulative prospect theory (CPT), in which the criteria values are expressed in various mathematical forms (e.g., real numbers, interval numbers, and linguistic terms) and can be changed with natural states of the epidemic. Initially, the detailed description of video conferencing software selection problem under an epidemic are given. Subsequently, a whole procedure for video conferencing software selection is conducted, the approaches for processing and normalizing the multi-format evaluation values are presented. Furthermore, the expectations provided by DMs under different natural states of the epidemic are considered as the corresponding reference points (RP). Based on this, the matrix of gains and losses is constructed. Then, the prospect values of all criteria and the perceived probabilities of natural states are calculated according to the value function and the weighting function in CPT respectively. Finally, the proposed method is illustrated by an empirical case study, and the comparison analysis and the sensitivity analysis for the loss aversion parameter are conducted to prove the effectiveness and robustness. The results show that considering the psychological characteristics of DMs in selection decision is beneficial to avoid the unacceptable and potential loss risks. This study could provide a useful guideline for managers who intend to select appropriate video conferencing software. [ABSTRACT FROM AUTHOR] Copyright of Journal of Intelligent & Fuzzy Systems is the property of IOS Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Follow-up testing of viral nucleic acids in patients with COVID-19 in Dazu district, Chongqing, China

To investigate the recurrence rate of coronavirus disease 2019(COVID-19) after discharge and type of SARS-CoV-Z nucleic acid-positive samples from patients with recurrence of SARS-CoV-Z in Dazu District, Chongqing, China, all patients were kept in isolation for 14 days, then quarantined at home for 4 weeks after discharge, during which time nasopharyngeal swabs, oropharyngeal swabs, feces, saliva, and urine were collected to test for SARS-CoV-Z nucleic acids by RT-PCR, and symptoms and signs were documented. Results showed that there were no symptoms or signs during isolation for any patient. However, specimens from three patients were confirmed positive for SARS-CoV-Z nucleic acids 3 to 14 days after discharge. SARS- CoV-Z nucleic acids were detected in saliva samples from two patients with recurrence of SARS-CoV-Z. The present study suggested that there is a relatively high incidence of positive tests for SARS-CoV-Z nucleic acids in patients after discharge. This is the first time that SARS-CoV-Z nucleic acids were detected in saliva samples. Whether the virus is infectious in these patients requires further study.

A comprehensive survey of bat sarbecoviruses across China for the origin tracing of SARS-CoV and SARS-CoV-2 (preprint)

Severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 have been thought to originate from bat, but whether the cross-species transmission occurred directly from bat to human or through an intermediate host remains elusive. In this study, we performed CoV screening of 102 samples collected from animal-selling stalls of Wuhan Huanan Market (WHM) and pharyngeal and anal swabs from13,064 bats collected at 703 locations across China, covering almost all known southern hotspots for sarbecovirus, between 2016 and 2021. This is the first systematic survey of bat CoV in China during the outbreak of Corona Virus Disease 2019. We found four non-sarbeco CoVs in samples of WHM, and 142 SARS-CoV related CoVs (SARSr-CoV) and 4 recombinant CoVs in bats, of which YN2020B-G share the highest sequence identity with SARS-CoV among all known bat CoVs, suggesting endemic SARSr-CoVs in bats in China. However, we did not find any SARS-CoV-2 related CoVs (SC2r-CoV) in any samples, including specimens collected from the only two domestic places where RaTG13 and RmYN02 were previously reported (the Tongguan caves and the karst caves around the Xishuangbanna Tropical Botanical Garden), indicating that SC2r-CoVs might not actively circulate among bats in China. Phylogenetic analysis showed that there are three different lineages of sarbecoviruses, L1 (SARSr-CoV), L2 (SC2r-CoV), and L-R (a novel CoV lineage from L1 and L2 recombination), in China. Of note, L-R CoVs are only found in R. pusillus. Further macroscopical analysis of the genetic diversity, host specificity for colonization and accidental infection, and geographical characteristics of available CoVs in database revealed the presence of a general geographical distribution pattern for bat sarbecoviruses, with the highest genetic diversity and sequence homology to SARS-CoV or SARS-CoV-2 along the southwest border of China, the least in the northwest of China. Considering the receptor binding motifs for spike gene of sarbecoviruses in Indochina Peninsula show the greatest diversity, our data provide the rationale that extensive surveys in further south and southwest to or of China might be needed for finding closer ancestors of SARS-CoV and SARS-CoV-2.

Whole genome sequencing identifies multiple loci for critical illness caused by COVID-19 (preprint)

Critical illness in COVID-19 is caused by inflammatory lung injury, mediated by the host immune system. We and others have shown that host genetic variation influences the development of illness requiring critical care1 or hospitalisation2;3;4 following SARS-Co-V2 infection. The GenOMICC (Genetics of Mortality in Critical Care) study is designed to compare genetic variants in critically-ill cases with population controls in order to find underlying disease mechanisms. Here, we use whole genome sequencing and statistical fine mapping in 7,491 critically-ill cases compared with 48,400 population controls to discover and replicate 22 independent variants that significantly predispose to life-threatening COVID-19. We identify 15 new independent associations with critical COVID-19, including variants within genes involved in interferon signalling (IL10RB, PLSCR1), leucocyte differentiation (BCL11A), and blood type antigen secretor status (FUT2). Using transcriptome-wide association and colocalisation to infer the effect of gene expression on disease severity, we find evidence implicating expression of multiple genes, including reduced expression of a membrane flippase (ATP11A), and increased mucin expression (MUC1), in critical disease. We show that comparison between critically-ill cases and population controls is highly efficient for genetic association analysis and enables detection of therapeutically-relevant mechanisms of disease. Therapeutic predictions arising from these findings require testing in clinical trials.

JDSR-GAN: Constructing A Joint and Collaborative Learning Network for Masked Face Super-Resolution (preprint)

With the growing importance of preventing the COVID-19 virus, face images obtained in most video surveillance scenarios are low resolution with mask simultaneously. However, most of the previous face super-resolution solutions can not handle both tasks in one model. In this work, we treat the mask occlusion as image noise and construct a joint and collaborative learning network, called JDSR-GAN, for the masked face super-resolution task. Given a low-quality face image with the mask as input, the role of the generator composed of a denoising module and super-resolution module is to acquire a high-quality high-resolution face image. The discriminator utilizes some carefully designed loss functions to ensure the quality of the recovered face images. Moreover, we incorporate the identity information and attention mechanism into our network for feasible correlated feature expression and informative feature learning. By jointly performing denoising and face super-resolution, the two tasks can complement each other and attain promising performance. Extensive qualitative and quantitative results show the superiority of our proposed JDSR-GAN over some comparable methods which perform the previous two tasks separately.

Decoding the RNA viromes in rodent lungs to understand rodent-borne pathogens (preprint)

Most human infectious viral diseases – including COVID-19 and Ebola – originated in animals. As the largest group of mammalian species, rodents are natural reservoirs for many diverse zoonotic viruses. Better understanding the core rodent virome will reduce the risk of future emergence or re-emergence of rodent-borne pathogens. A recent study focused on viruses found in the lungs of rodents in Mainland Southeast Asia, a hotspot for zoonotic emerging infectious diseases. Lung samples were collected from 3,284 rodents and insectivores throughout Thailand, Lao PDR, and Cambodia. Using metatranscriptomics, researchers outlined unique characteristics of the rodent viruses identified. Many mammalian- or arthropod-related viruses from distinct evolutionary lineages were reported for the first time, and viruses related to known pathogens were found. These results expand our understanding of the core virome in rodent species in Mainland Southeast Asia and suggest that a highly diverse array of viruses remains to be found in these species. Viral surveillance in wildlife hosts will minimize the impact of potential wildlife-originating infectious diseases.

Organizing Pneumonia of COVID-19: Time-dependent Evolution and Outcome in CT Findings (preprint)

Objective: As a pandemic, a most-common pattern resembled organizing pneumonia (OP) has been identified by CT findings in novel coronavirus disease (COVID-19). We aimed to delineate the evolution of CT findings and outcome in OP of COVID-19. Materials and Methods: 106 COVID-19 patients with OP based on CT findings were retrospectively included and categorized into non-severe (mild/common) and severe (severe/critical) groups. CT features including lobar distribution, presence of ground glass opacities (GGO), consolidation, linear opacities and total severity CT score were evaluated at three time intervals from symptom-onset to CT scan (day 0-7, day 8-14, day>14). Discharge or adverse outcome (admission to ICU or death), and pulmonary sequelae (complete absorption or lesion residuals) on CT after discharge were analyzed based on the CT features at different time interval. Results: 79(74.5%) patients were non-severe and 103(97.2%) were discharged at median day 25 (range, day 8-50) after symptom-onset. Of 67 patients with revisit CT at 2-4 weeks after discharge, 20(29.9%) had complete absorption of lesions at median day 38 (range, day 30-53) after symptom-onset. Significant differences between complete absorption and residuals groups were found in percentages of consolidation (1.5% vs. 13.8%, P=0.010), number of involved lobe >3 (40.0% vs. 72.5%, P=0.030), CT score >4 (20.0% vs. 65.0%, P=0.010) at day 8-14. Conclusions: Most OP cases had good prognosis. Approximately one-third of cases had complete absorption of lesions during 1-2 months after symptom-onset while those with increased frequency of consolidation, number of involved lobe>3, and CT score >4 at week 2 after symptom-onset may indicate lesion residuals on CT.

Differences of clinical and imaging findings in multiple generations of secondary COVID-19 infection in Xi'an, China (preprint)

PURPOSE: In the global presence of secondary infections with the coronavirus disease 2019 (COVID-19), little is known about the transmission characteristics of COVID-19 outside Wuhan, China. We evaluated differences in clinic and radiologic findings of multiple generations of COVID-19 infection in Xi'an (Shaanxi, China) to provide more clues for the correct estimate of the disease. METHODS: All COVID-19 infected patients reported in Xi'an up to 10 February 2020 were included for this analysis. Among these cases, clinical and chest CT data of 62 cases were obtained from three hospital in Xi'an. With this information, patients were grouped on basis of exposure history and transmission chains as first-generation, second-generation and third-generation patients. We described clinical characteristics and evaluated CT score/patterns in these COVID-19 cases. RESULTS: There was a clear age differences in multiple generations with COVID-19 infection. Above two thirds of the second-generation (75.0%) and third-generation patients (77.8%) were aged [≥]45 years while 40.0% of first-generation cases at this age (p=0.001). More than half of second-generation patients (52.8%) and third-generation patients (55.6%) have comorbidities and is predominantly hypertensive (22.8% of second-generation vs. 27.8% of third-generation infections). The main exposure of second- and third-generation patients in Xi'an is family exposure (35.2%). For evaluation of CT findings of pulmonary involvement, the total CT score were 4.22{+/-}3.00 in first-generation group, 4.35{+/-}3.03 in second-generation group and 7.62{+/-}3.56 in third-generation group (p<0.001). In all of three generations, the predominant pattern of abnormality observed was organizing pneumonia (65.5% in first-generation group, 61.5% in second-generation group and 71.4% in third-generation group). The average courses of the disease in third-generation infections has obviously extension (22.93{+/-}7.22 days of first-generation, 21.53{+/-}8.31 days of second-generation vs. 31.00{+/-}8.12 days of third-generation group, p=0.004). There were no significant differences of the pulmonary sequelae among three generation patients. CONCLUSION: There is more serious pulmonary infection of COVID-19 pneumonia in second- and third-generation patients, which might be attribute to the elder age and comorbidity of these patients.

A pattern categorization of CT findings to predict outcome of COVID-19 pneumonia (preprint)

AbstractsO_ST_ABSPurposeC_ST_ABSAs global healthcare system is overwhelmed by novel coronavirus disease (COVID-19), early identification of risks of adverse outcomes becomes the key to optimize management and improve survival. This study aimed to provide a CT-based pattern categorization to predict outcome of COVID-19 pneumonia. Methods165 patients with COVID-19 (91 men, 4-89 years) underwent chest CT were retrospectively enrolled. CT findings were categorized as Pattern0 (negative), Pattern1 (bronchopneumonia), Pattern2 (organizing pneumonia), Pattern3 (progressive organizing pneumonia) and Pattern4 (diffuse alveolar damage). Clinical findings were compared across different categories. Time-dependent progression of CT patterns and correlations with clinical outcomes, i.e. discharge or adverse outcome (admission to ICU, requiring mechanical ventilation, or death), with pulmonary sequelae (complete absorption or residuals) on CT after discharge were analyzed. ResultsOf 94 patients with outcome, 81(86.2%) were discharged, 3(3.2%) were admitted to ICU, 4(4.3%) required mechanical ventilation, 6(6.4%) died. 31(38.3%) had complete absorption at median day 37 after symptom-onset. Significant differences between pattern-categories were found in age, disease-severity, comorbidity and laboratory results (all P<0.05). Remarkable evolution was observed in Pattern0-2 and Pattern3-4 within 3 and 2 weeks after symptom-onset, respectively; most of patterns remained thereafter. After controlling for age, CT pattern significantly correlated with adverse outcomes (Pattern4 vs. Pattern0-3 [reference]; hazard-ratio[95%CI], 18.90[1.91-186.60], P=0.012). CT pattern (Pattern3-4 vs. Pattern0-2 [reference]; 0.26[0.08-0.88], P=0.030) and C-reactive protein (>10 vs. [≤]10mg/L [reference]; 0.31[0.13-0.72], P=0.006) were risk-factors associated with pulmonary residuals. ConclusionCT pattern categorization allied with clinical characteristics within 2 weeks after symptom-onset would facilitate early prognostic stratification in COVID-19 pneumonia.

Heightened innate immune responses in the respiratory tract of COVID-19 2 patients

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV44 2 infection has posed a severe threat to global public health. It is unclear how the human 45 immune system responds to this infection. Here, we used metatranscriptomic 46 sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight 47 COVID-19 cases. The expression of proinflammatory genes, especially chemokines, 48 was markedly elevated in COVID-19 cases compared to community-acquired 49 pneumonia patients and healthy controls,suggesting that SARS-CoV-2 infection causes 50 hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate 51 interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous 52 IFN-inducible genes (ISGs). These ISGs exhibit immunopathogenic potential, with 53 overrepresentation of genes involved in inflammation. The transcriptome data was also 54 used to estimate immune cell populations, revealing increases in activated dendritic 55 cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection 3 56 could further our understanding of disease pathogenesis and point towards antiviral 57 strategies.

The Reversed Halo Sign in COVID-19 Pneumonia (preprint)

ObjectivesTo evaluate the frequency and time course of RHS on CT in patient with COVID-19 pneumonia.Materials and methodsA total of 147 patients with COVID-19 pneumonia were divided into mild, moderate, severe and critical categories. The number, location, shape, wall appearance of RHS on CT were analyzed. Other parenchymal abnormalities include GGO, consolidation and linear opacity were also recorded.ResultsRHS was observed in 37 (25.2%) of 147 patients and it was more common in patients with moderate disease than severe or critical disease (31.3% vs. 13.0%, P = 0.019). Time from symptom onset to appearance of RHS was 9 ± 5 days in moderate patients and 14 ± 8 days in severe/critical patients. A total of 64 RHS lesions were identified and the majority of lesions were located in peripheral aspect of lungs (55, 85.9%) and lower lobes (52, 81.2%). All lesions with RHS were round or oval-shaped. The rim of RHS were smooth in 54 (84.4%) and irregular in 10 (15.6%). Follow-up CT scans of 27 patients (50 lesions) showed 43(86%) lesions gradually resolved or developed into GGO and linear opacities and 7(14%) lesions remained unchanged appearance.ConclusionsRHS occurred sooner after symptom onset and with higher frequency in patients with moderate compared to those with severe or critical disease. RHS may represent a favorable prognostic sign in COVID-19 pneumonia.Key Points• 37 (25.2%) of 147 patients with COVID-19 pneumonia had RHS on at least one CT• RHS was more prevalent in patients with moderate disease than those with severe or critical disease• RHSs (78.4%) mostly occurred within 2 weeks after symptom onset