Predictive Systems Biology Modeling: Unraveling Host Metabolic Disruptions and Potential Drug Targets in SARS-CoV-2 and Its Variants (preprint)

Background: Host response is critical to the onset, progression, and outcome of viral infections. Since viruses hijack the host cellular metabolism for their replications, we hypothesized that restoring host cell metabolism can efficiently reduce viral production. Here, we present a viral-host Metabolic Modeling (vhMM) method to systematically evaluate the disturbances in host metabolism in viral infection and computationally identify targets for modulation by integrating genome-wide precision metabolic modeling and cheminformatics. Results: In SARS-CoV-2 infections, we identified consistent changes in host metabolism and gene and endogenous metabolite targets between the original SARS-COV-2 and different variants (Alpha, Delta, and Omicron). Among six compounds predicted for repurposing, methotrexate, cinnamaldehyde, and deferiprone were tested in vitro and effective in inhibiting viral production with IC50 less than 4uM. Further, an analysis of real-world patient data showed that cinnamon usage significantly reduced the SARS-CoV-2 infection rate with an odds ratio of 0.65 [95%CI: 0.55~0.75]. Conclusions: These results demonstrated that vhMM is an efficient method for predicting targets and drugs for viral infections.

Identification of Host Proteins Interacting with IBV S1 Based on Tracheal Organ Culture.

Infectious bronchitis virus (IBV) belongs to the gamma-coronavirus genus of Coronaviridae and causes serious infectious diseases in the poultry industry. However, only a few IBV strains can infect avian passage cell lines, seriously hindering the progress of basic research on IBV pathogenesis. Whereas IBV field strains can replicate in tracheal ring organ culture (TOC) without any previous adaptation in chicken embryos or primary cells. In this study, to investigate the potential use of TOC as an in vitro infection model for the study of IBV-host interaction, we first established a chicken embryo TOC culture system and carried out an investigation on the IBV replication kinetics in the system. We found that the selected strains of the IBV GI-1, GI-7, GI-13, GI-19, and GI-22 genotypes could successfully replicate in TOC and bring about damage to the infected trachea. Next, we identified host proteins of the chicken embryo trachea that interact with the IBV S1 protein by immunoprecipitation and protein mass spectrometry. A total of 127 candidate proteins were initially identified with major involvement in cell adhesion pathways and apoptosis- and autophagy-related pathways. The heat shock protein 70 (HSP70) was selected for further investigation in the interaction with IBV viral proteins. Our results showed that HSP70 interacted with IBV S1 in both TOC and CEK cells, whereas HSP70 overexpression inhibited viral replication. This study indicates that TOC is a good system for the elucidation of IBV-host interactions and HSP70 is a potential host antiviral factor.

The Relationship Between Physical Activity and Mobile Phone Addiction Among Adolescents and Young Adults: Systematic Review and Meta-analysis of Observational Studies.

BACKGROUND: Previous studies have reported a potential negative correlation between physical activity (PA) and mobile phone addiction (MPA) among adolescents and young adults. To date, the strength of this correlation has not been well characterized. OBJECTIVE: This review and meta-analysis aimed to synthesize available empirical studies to examine the correlations between PA and MPA among adolescents and young adults. We also explored several potential moderators, including time of data collection, country or region, and type of population, associated with the relationship between PA and MPA. METHODS: Four electronic databases (PubMed, Scopus, PsycINFO, and Web of Science) were searched from database inception to March 2022 to identify relevant studies. The pooled Pearson correlation coefficients and their corresponding 95% CIs for the relationship between PA and MPA were calculated using the inverse variance method. The methodological quality of the included cross-sectional studies was determined based on the Joanna Briggs Institute appraisal checklist. The study conformed to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-analyses) guidelines. RESULTS: In total, 892 relevant articles were identified, of which 22 were selected based on the inclusion and exclusion criteria. The final meta-analysis included 17 of the 22 studies. Results of random effects modeling revealed a moderate correlation between PA and MPA among adolescents and young adults (summary r=-0.243, P<.001). Sensitivity and publication bias analyses further demonstrated the robustness of our results. All the included studies were scored as high quality with a low risk of bias. Subgroup analysis further indicated that none of the hypothesized moderators (time of data collection, country or region, and type of population) significantly affected the relationship between PA and MPA, as confirmed by the mixed effects analysis. In addition, in the data collection subgroups, medium effect sizes were obtained for data collected before COVID-19 (r=-0.333, P<.001) and data collected during COVID-19 (r=-0.207, P<.001). In subgroup analyses for country or region, the correlation coefficient for China and other developing regions showed a similarly moderate effect size (r=-0.201, P<.001 and r= -0.217, P<.001, respectively). However, the effect sizes for developed regions were not significant (r=-0.446, P=.39). In a subgroup analysis based on the type of population, we found that the effect size for young adults was moderate (r=-0.250, P<.001). However, that of adolescents was not significant (r=-0.129, P=.24). CONCLUSIONS: Our results demonstrate a moderately negative relationship between PA and MPA among young adults. The strength of this relationship was not influenced by the time of data collection, country or region, or type of population.

What contributes to the re-positive nucleic acid test results for the omicron variant of SARS-CoV-2 in the shelter cabin hospital in Shanghai, China?

Background: Despite the increasing reports of re-positive SARS-CoV-2 cases after recovery and discharge from hospitals, our knowledge remains very limited regarding the contributing factors of re-positivity and its roles in the transmission and epidemiology of the Omicron variant. Methods: In this retrospective study, re-positivity is defined as the positive nucleic acid result (Ct < 35) following two consecutive negative results during hospitalization. A total of 751 patients from Shanghai Shelter Cabin Hospital were enrolled and divided with a ratio of about 1:2 into the re-positivity group and the non-re-positivity group. Patients required three consecutive negative results daily as the de-isolation criterion. The follow-up time of discharged patients lasted five weeks. Univariate regression analysis was used to compare variables between the re-positivity and non-re-positivity groups, and the single re-positivity and multiple re-positivity groups, with P < 0.05 defined as the statistical significance of differences. Subsequently, variables with P < 0.2 were subjected to multivariate logistic regression analysis to investigate the odds ratio (OR) of re-positivity and the influencing factors of re-positivity of the Omicron variant. Results: The re-positivity group had a higher proportion of males (68.1% vs 58.1%, p = 0.000), a higher education level (31.9% vs 12.7%, p = 0.007), a longer hospitalization duration (13 days vs 8 days, p = 0.000), and a higher Convidecia vaccination rate (6.0% vs 2.4%, p = 0.011). Further multivariable analysis showed male (OR = 2.168, p = 0.000), Convidecia vaccination (OR = 2.634, p = 0.014), hospitalization duration (OR = 2.146, p = 0.000) and education level (OR = 1.595, p = 0.007) were associated with re-positivity. The average rate of re-positivity was 25% during hospitalization and decreased to 0.4% among discharged patients. Re-positivity was more common in the period with a larger number of hospitalized patients and in larger wards with a larger number of patients. Conclusion: A large number of hospitalized patients, large-sized wards, and gender are significant contributing factors to re-positivity. Division of the shelter cabin hospital into small independent wards and requirement of three consecutive results daily as the de-isolation criterion might be more beneficial to the control and prevention of the spread of the Omicron variant.

Antibiotic expectation, behaviour, and receipt among patients presenting to emergency departments with uncomplicated upper respiratory tract infection during the COVID-19 pandemic

OBJECTIVES Pre-COVID-19 pandemic, patients who attended the emergency department (ED) for upper respiratory tract infection (URTI) were more likely to receive antibiotics if they expected them. These expectations could have changed with the change in health-seeking behaviour during the pandemic. We assessed the factors associated with antibiotics expectation and receipt for uncomplicated URTI patients in four Singapore EDs during the COVID-19 pandemic. METHODS We conducted a cross-sectional study on adult patients with URTI from March 2021 to March 2022 in four Singapore EDs and assessed the determinants of antibiotics expectation and receipt using multivariable logistic regression models. We also assessed the reasons patients expect antibiotics during their ED visit. RESULTS Among 681 patients, 31.0% expected antibiotics while 8.7% received antibiotics during their ED visit. Factors [adjusted odds ratio (95% confidence interval)] that significantly influenced expectation for antibiotics include: 1) prior consultation for current illness with [6.56 (3.30-13.11)] or without [1.50 (1.01-2.23)] antibiotics prescribed;2) anticipation for COVID-19 test [1.56 (1.01-2.41)];and 3) poor [2.16 (1.26-3.68)] to moderate [2.26 (1.33-3.84)] knowledge on antibiotics use and resistance. Patients expecting antibiotics were 10.6 times [10.64 (5.34-21.17)] more likely to receive antibiotics. Those with tertiary education were twice [2.20 (1.09-4.43)] as likely to receive antibiotics. CONCLUSIONS In conclusion, patients with URTI who expected antibiotics to be prescribed remained more likely to receive it during the COVID-19 pandemic. This highlights the need for more public education on the non-necessity for antibiotics for URTI and COVID-19 to address the problem of antibiotic resistance.

A multi-institutional exploration of emergency medicine physicians' attitudes and behaviours on antibiotic use during the COVID-19 pandemic: a mixed-methods study.

BACKGROUND: The COVID-19 pandemic has changed the epidemiology of upper respiratory tract infections (URTI) and the disease profile of patients attending the emergency department (ED). Hence, we sought to explore the changes in ED physicians' attitudes and behaviours in four EDs in Singapore. METHODS: We employed a sequential mixed-methods approach (quantitative survey followed by in-depth interviews). Principal component analysis was performed to derive latent factors, followed by multivariable logistic regression to explore the independent factors associated with high antibiotic prescribing. Interviews were analysed using the deductive-inductive-deductive framework. We derive five meta-inferences by integrating the quantitative and qualitative findings with an explanatory bidirectional framework. RESULTS: We obtained 560 (65.9%) valid responses from the survey and interviewed 50 physicians from various work experiences. ED physicians were twice as likely to report high antibiotic prescribing rates pre-COVID-19 pandemic than during the pandemic (AOR = 2.12, 95% CI 1.32 to 3.41, p = 0.002). Five meta-inferences were made by integrating the data: (1) Less pressure to prescribe antibiotics due to reduced patient demand and more patient education opportunities; (2) A higher proportion of ED physicians self-reported lower antibiotic prescribing rates during the COVID-19 pandemic but their perception of the overall outlook on antibiotic prescribing rates varied; (3) Physicians who were high antibiotic prescribers during the COVID-19 pandemic made less effort for prudent antibiotic prescribing as they were less concerned about antimicrobial resistance; (4) the COVID-19 pandemic did not change the factors that lowered the threshold for antibiotic prescribing; (5) the COVID-19 pandemic did not change the perception that the public's knowledge of antibiotics is poor. CONCLUSIONS: Self-reported antibiotic prescribing rates decreased in the ED during the COVID-19 pandemic due to less pressure to prescribe antibiotics. The lessons and experiences learnt from the COVID-19 pandemic can be incorporated into public and medical education in the war against antimicrobial resistance going forward. Antibiotic use should also be monitored post-pandemic to assess if the changes are sustained.

Antibiotic expectation, behaviour, and receipt among patients presenting to emergency departments with uncomplicated upper respiratory tract infection during the COVID-19 pandemic.

OBJECTIVES: Pre-COVID-19 pandemic, patients who attended the emergency department (ED) for upper respiratory tract infection (URTI) were more likely to receive antibiotics if they expected them. These expectations could have changed with the change in health-seeking behaviour during the pandemic. We assessed the factors associated with antibiotics expectation and receipt for uncomplicated URTI patients in four Singapore EDs during the COVID-19 pandemic. METHODS: We conducted a cross-sectional study on adult patients with URTI from March 2021 to March 2022 in four Singapore EDs and assessed the determinants of antibiotics expectation and receipt using multivariable logistic regression models. We also assessed the reasons patients expect antibiotics during their ED visit. RESULTS: Among 681 patients, 31.0% expected antibiotics while 8.7% received antibiotics during their ED visit. Factors (adjusted odds ratio [95% confidence interval]) that significantly influenced expectation for antibiotics include: 1) prior consultation for current illness with (6.56 [3.30-13.11]) or without (1.50 [1.01-2.23]) antibiotics prescribed; 2) anticipation for COVID-19 test (1.56 [1.01-2.41]); and 3) poor (2.16 [1.26-3.68]) to moderate (2.26 [1.33-3.84]) knowledge on antibiotics use and resistance. Patients expecting antibiotics were 10.6 times (10.64 [5.34-21.17]) more likely to receive antibiotics. Those with tertiary education were twice (2.20 [1.09-4.43]) as likely to receive antibiotics. CONCLUSION: In conclusion, patients with URTI who expected antibiotics to be prescribed remained more likely to receive it during the COVID-19 pandemic. This highlights the need for more public education on the non-necessity for antibiotics for URTI and COVID-19 to address the problem of antibiotic resistance.

[Effect of Family Environment on Non-Suicidal Self-Injury Among Middle School Students During the COVID-19 Epidemic: The Mediating Role of Depression].

Objective: To study the current status of non-suicidal self-injury (NSSI) incidents among middle school students in Chengdu during the COVID-19 epidemic and to explore the mechanism of action of depression on the relationship between family environment and NSSI. Methods: Data were obtained from the Chengdu Positive Child Development (CDPD) cohort. In June and July 2020, after primary and secondary schools were reopened after the closure due to the COVID-19 epidemic, on-site questionnaire surveys were conducted with the Deliberate Self-Harm Inventory (DSHI), the Chinese Family Assessment Instrument (C-FAI), and Center for Epidemiologic Studies Depression Scale for Children (CES-DC), thereby obtaining the data of 3595 middle school students. Two-sample t-test and χ 2 test were used to compare the incidence of NSSI among middle school students of different grades and genders, and the Model 58 test of the SPSS PROCESS component was used to analyze the mediating effect of gender-mediated depression. Results: 1) The incidence of NSSI among middle school students in Chengdu during the COVID-19 epidemic was 49.67%. The incidence of NSSI among ninth-graders (80.70%) was significantly higher than those of the eighth graders (33.82%) and seventh graders (32.32%), and the incidence of NSSI among female middle school students (54.75%) was significantly higher than that of male students (44.52%). 2) Family environment ( r=0.34, P<0.001) and depression ( r=0.50, P<0.001) were positively correlated with NSSI. 3) Depression partially mediated the effect of family environment on NSSI, with the mediating effect accounting for 64.64% of the total effect. Compared with that of male students, the positive predictive effect between family environment and depression and that between depression and NSSI in female middle school students were more significant. Conclusion: During the COVID-19 pandemic, middle school students in Chengdu had a high incidence of NSSI, which indicates that the family environment should be improved, more attention should be given to gender differences, and early screening and intervention for depression should be strengthened to reduce the incidence of NSSI.

BCG-induced trained immunity: history, mechanisms and potential applications.

The Bacillus Calmette-Guérin (BCG) vaccine was discovered a century ago and has since been clinically applicable. BCG can not only be used for the prevention of tuberculosis, but also has a non-specific protective effect on the human body called trained immunity that is mediated by innate immune cells such as monocytes, macrophages, and natural killer cells. Mechanisms of trained immunity include epigenetic reprogramming, metabolic reprogramming, and long-term protection mediated by hematopoietic stem cells. Trained immunity has so far shown beneficial effects on cancer, viral-infections, autoimmune diseases, and a variety of other diseases, especially bladder cancer, respiratory viruses, and type 1 diabetes. The modulation of the immune response by BCG has led to the development of a variety of recombinant vaccines. Although the specific mechanism of BCG prevention on diseases has not been fully clarified, the potential role of BCG deserves further exploration, which is of great significance for prevention and treatment of diseases.

Viral contamination on the surfaces of the personal protective equipment among health care professionals working in COVID-19 wards: A single-center prospective, observational study.

OBJECTIVE: To evaluate potential viral contamination on the surfaces of personal protective equipment (PPE) in COVID-19 wards. METHODS: Face shields, gloves, the chest area of PPE and shoe soles were sampled at different time points. The samples were tested for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by PCR, and the cycle threshold (CT) values were recorded. RESULTS: The positive rate was 74.7% (239/320) for all PPE specimens. The CT values of the samples were ranked in the following order: face shields > chests > gloves > shoe soles (37.08±1.38, 35.48±2.02, 34.17±1.91 and 33.52±3.16, respectively; P for trend < .001). After disinfection, the CT values of shoe soles decreased compared with before disinfection (32.78±3.47 vs. 34.3±2.61, P = .037), whereas no significant effect of disinfection on the CT values of face shields, chests and gloves was observed. After disinfection, the CT values of specimens collected from shoe soles gradually increased; before disinfection, the CT values of shoe sole specimens were all less than 35. CONCLUSIONS: SARS-CoV-2 can attach to the surfaces of the PPE of healthcare professionals in COVID-19 wards, especially the shoe soles and undisinfected gloves. Shoe soles had the highest SARS-CoV-2 loads among all tested PPE items.

Detection of hospital environmental contamination during SARS-CoV-2 Omicron predominance using a highly sensitive air sampling device.

Background and objectives: The high transmissibility of SARS-CoV-2 has exposed weaknesses in our infection control and detection measures, particularly in healthcare settings. Aerial sampling has evolved from passive impact filters to active sampling using negative pressure to expose culture substrate for virus detection. We evaluated the effectiveness of an active air sampling device as a potential surveillance system in detecting hospital pathogens, for augmenting containment measures to prevent nosocomial transmission, using SARS-CoV-2 as a surrogate. Methods: We conducted air sampling in a hospital environment using the AerosolSenseTM air sampling device and compared it with surface swabs for their capacity to detect SARS-CoV-2. Results: When combined with RT-qPCR detection, we found the device provided consistent SARS-CoV-2 detection, compared to surface sampling, in as little as 2 h of sampling time. The device also showed that it can identify minute quantities of SARS-CoV-2 in designated "clean areas" and through a N95 mask, indicating good surveillance capacity and sensitivity of the device in hospital settings. Conclusion: Active air sampling was shown to be a sensitive surveillance system in healthcare settings. Findings from this study can also be applied in an organism agnostic manner for surveillance in the hospital, improving our ability to contain and prevent nosocomial outbreaks.

Detection of hospital environmental contamination during SARS-CoV-2 Omicron predominance using a highly sensitive air sampling device

Background and objectives The high transmissibility of SARS-CoV-2 has exposed weaknesses in our infection control and detection measures, particularly in healthcare settings. Aerial sampling has evolved from passive impact filters to active sampling using negative pressure to expose culture substrate for virus detection. We evaluated the effectiveness of an active air sampling device as a potential surveillance system in detecting hospital pathogens, for augmenting containment measures to prevent nosocomial transmission, using SARS-CoV-2 as a surrogate. Methods We conducted air sampling in a hospital environment using the AerosolSenseTM air sampling device and compared it with surface swabs for their capacity to detect SARS-CoV-2. Results When combined with RT-qPCR detection, we found the device provided consistent SARS-CoV-2 detection, compared to surface sampling, in as little as 2 h of sampling time. The device also showed that it can identify minute quantities of SARS-CoV-2 in designated "clean areas” and through a N95 mask, indicating good surveillance capacity and sensitivity of the device in hospital settings. Conclusion Active air sampling was shown to be a sensitive surveillance system in healthcare settings. Findings from this study can also be applied in an organism agnostic manner for surveillance in the hospital, improving our ability to contain and prevent nosocomial outbreaks.

Depression and anxiety of medical students at Kunming Medical University during COVID-19: A cross-sectional survey.

An isolation strategy was used to control the transmission and rapid spread of COVID-19 in Yunnan. As a result, students were supposed to stay at home and disrupted their outside activities. It led to a detrimental influence on students' mental health. The purpose of this study was to investigate the prevalence and risk factors of depression and anxiety among medical students and to provide ideas for the prevention of depression and anxiety in medical students. A cross-sectional survey was conducted among 2,116 medical students at Kunming Medical University from July 8 to July 16, 2020. Participants' demographic and living conditions were collected. Depression and anxiety were measured using the Patient Health Questionnaire 9 and General Anxiety Disorder-7, respectively. Uni- and multivariate logistic regression analyses were performed to detect risk factors associated with depression and anxiety. The prevalence rates of depression and anxiety among medical students were 52.5 and 29.6%, respectively. Depression was more likely to be caused by low grades, lack of physical exercise, drug use, irregular diet, extensive screen time on mobile phones, being greatly affected by the COVID-19 pandemic, and inadaptability to offline courses. Anxiety was more likely to be caused by lack of physical exercise, drug use, irregular diet, and inadaptability to offline courses. Depression and anxiety are highly comorbid. Our study showed predictive factors for depression and anxiety and identified a major mental health burden on medical students during the COVID-19 outbreak. More targeted measures should be taken to improve the mental state of students to reduce the incidence of depression and anxiety.

Lung Organoids as Model to Study SARS-CoV-2 Infection.

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has severely affected socio-economic conditions and people's life. The lung is the major target organ infected and (seriously) damaged by SARS-CoV-2, so a comprehensive understanding of the virus and the mechanism of infection are the first choices to overcome COVID-19. Recent studies have demonstrated the enormous value of human organoids as platforms for virological research, making them an ideal tool for researching host-pathogen interactions. In this study, the various existing lung organoids and their identification biomarkers and applications are summarized. At the same time, the seven coronaviruses currently capable of infecting humans are outlined. Finally, a detailed summary of existing studies on SARS-CoV-2 using lung organoids is provided and includes pathogenesis, drug development, and precision treatment. This review highlights the value of lung organoids in studying SARS-CoV-2 infection, bringing hope that research will alleviate COVID-19-associated lung infections.

Effectiveness of Social Video Platforms in Promoting COVID-19 Vaccination Among Youth: A Content-Specific Analysis of COVID-19 Vaccination Topic Videos on Bilibili.

Background: With the widespread promotion of the COVID-19 vaccination in China, videos about the vaccination have become increasingly available on social video platforms. With the User Generated Content model, different creators' interpretations of COVID-19 vaccines may influence the attitudes towards the vaccines and vaccination. Objective: To explore the overview of COVID-19 vaccine-related videos on Bilibili, discussing the communication effects of COVID-19 topic videos and its influencing factors. Methods: A content analysis was applied to the 202 video samples obtained through data mining regarding the creator's information, video presentation, and COVID-19 vaccine-related content. Results: Individuals and medical professionals preferred VLOG videos, media chose to upload informational videos, and enterprises preferred to post showcase videos. Individuals were more likely to discuss the adverse reactions in their videos, while medical professionals were more likely to discuss the vaccination process for the COVID-19 vaccine. Videos with core issues positively influenced the video's dissemination breadth. The attitudes toward the COVID-19 vaccine in the videos positively influence the recognition of the videos. The richness of knowledge points related to the COVID-19 vaccine negatively affected the recognition and participation. Conclusion: Social video platforms could play an active role in the vaccination promotion for the youth. Health promotion-related departments and individuals could strengthen agenda setting, grasp the characteristics of young groups, and express positive attitudes toward health issues to achieve better health (vaccine) promotion.

COVID-19 Vaccines in Older Adults: Challenges in Vaccine Development and Policy Making.

The coronavirus disease 2019 (COVID-19) pandemic has had strong adverse impacts on vulnerable populations, such as frail older adults. The success of COVID-19 vaccine development, together with extensive global public health efforts, has brought hope to the control of the COVID-19 pandemic. Nevertheless, challenges in COVID-19 vaccine development and vaccination strategies among older people remain. This article reviews vaccinations in older adults, compares COVID-19 vaccine platforms, the efficacy and safety of COVID-19 vaccines in frail older people in long-term care settings, and the challenges of COVID-19 vaccine development and policy making for vaccination strategies in older adults.

Latest developments in the upconversion nanotechnology for the rapid detection of food safety: A review

Food safety has become a topic of global concern in the recent decades. The significant food safety incidents occur from time to time around the world, seriously threatening the public health and causing extensive economic losses. In particular, the occurrence of COVID-19 highlights the importance of the food safety for the public health. Therefore, there is an urgent need to establish a fast, simple, sensitive, and efficient method for the detection of food safety. In recent years, the upconversion (UC) nanotechnology has been widely used in the field of food detection. The UC fluorescence analysis technology possesses the advantages of ultra-sensitivity detection, non-invasiveness, light stability, etc., and has broad application prospects in the field of food safety. After cladding and surface modification, it can be combined with other substances through a variety of mechanisms, such as electrostatic interaction, thereby expanding its application in the food safety detection. Thus, overall, there is a vital need to evaluate and utilize the potential of UC nanoparticles in the field of rapid detection of food safety.